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1
Ma, Xuhui, Qing Wang, Yanzhi Wang, et al. "Chromosome aberrations induced by zebularine in triticale." Genome 59, no. 7 (2016): 485–92. http://dx.doi.org/10.1139/gen-2016-0047.
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Chromosome engineering is an important approach for generating wheat germplasm. Efficient development of chromosome aberrations will facilitate the introgression and application of alien genes in wheat. In this study, zebularine, a DNA methylation transferase inhibitor, was successfully used to induce chromosome aberrations in the octoploid triticale cultivar Jinghui#1. Dry seeds were soaked in zebularine solutions (250, 500, and 750 μmol/L) for 24 h, and the 500 μmol/L treatment was tested in three additional treatment times, i.e., 12, 36, and 48 h. All treatments induced aberrations involving wheat and rye chromosomes. Of the 920 cells observed in 67 M1 plants, 340 (37.0%) carried 817 aberrations with an average of 0.89 aberrations per cell (range: 0–12). The aberrations included probable deletions, telosomes and acentric fragments (49.0%), large segmental translocations (28.9%), small segmental translocations (17.1%), intercalary translocations (2.6%), long chromosomes that could carry more than one centromere (2.0%), and ring chromosomes (0.5%). Of 510 M2 plants analyzed, 110 (21.6%) were found to carry stable aberrations. Such aberrations included 79 with varied rye chromosome numbers, 7 with wheat and rye chromosome translocations, 15 with possible rye telosomes/deletions, and 9 with complex aberrations involving variation in rye chromosome number and wheat–rye translocations. These indicated that aberrations induced by zebularine can be steadily transmitted, suggesting that zebularine is a new efficient agent for chromosome manipulation.
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Mandahl, Nils, Charlotte Örndal, Sverre Heim, et al. "Aberrations of chromosome segment 12q13–15 characterize a subgroup of hemangiopericytomas." Cancer 71, no. 10 (1993): 3009–13. http://dx.doi.org/10.1002/1097-0142(19930515)71:10<3009::aid-cncr2820711020>3.0.co;2-y.
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Chaudhry, Asha, Preety Bhinder, Ram Kumar, and Ravneet Kaur. "Evaluation of the mutagenic potential of propoxur and methyl parathion using polytene chromosomes of Anopheles stephensi." Journal of Applied and Natural Science 4, no. 1 (2012): 79–84. http://dx.doi.org/10.31018/jans.v4i1.227.
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The mutagenicity of two pesticides, propoxur and methyl parathion was evaluated by using polytene chromosomes of Anopheles stephensi. The results were based on the frequency of various structural aberrations encountered in the polytene chromosomes of the larvae treated with LC20 of propoxur and methyl parathion separately. Propoxur induced a total of 67 aberrations as against 15 in the controls while methyl parathion induced 53 aberrations as against 13 in the controls. These aberrations were dominated by inversions, translocations, deletions, ectopic pairing, asynapses, breaks, fusions and induced puffing. The frequency of propoxur induced aberrations was highest in chromosome 3R followed by 2R, 3L, 2L and X-chromosome. Methyl parathion induced highest number of aberrations in 2R followed by 2L, 3R, 3L and X-chromosomes. This study suggests that larval polytene chromosomes are sensitive indicators of pesticide genotoxicity in which both propoxur and methyl parathion are significantly chromotoxic for the genome of a mosquito taken as an experimental insect.
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Teodorović, Radislava, Vladimir Drašković, Spomenka Đurić, Kartarina Nenadović, Milorad Mirilović, and Ljiljana Janković. "Chromosome Aberrations Produced by Mestranol in Human Lymphocyte Cultures." Acta Veterinaria 69, no. 4 (2019): 426–33. http://dx.doi.org/10.2478/acve-2019-0036.
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Abstract In this investigation, the genotoxic properties of mestranol were examined in vitro. Human lymphocyte cultures were exposed for 72 h to mestranol at concentrations of 7.5, 15 and 30 µg/g. The genotoxic effects of the chemosterilant were assessed by numerical and structural chromosome aberrations. Mestranol induced certain genotoxic effects in human lymphocytes. There was a dose-dependent significant (p<0.01) increase in the number of numerical aberrations in comparison to the control, but without significant differences (p>0.05) between the doses applied. Further, structural aberrations increased significantly (p<0.01) in the presence of mestranol, being most frequent in cultures exposed to the highest mestranol dose. The frequency of Robertsonian translocations increased significantly only in cultures treated with mestranol at concentration of 30 µg/g in comparison both with the control (p<0.01) and the lowest chemosterilant dose (p<0.01). There were significant differences (p<0.01) in the levels of chromosome gaps and fragments compared to Robertsonian translocations, whilst the frequencies between gaps and fragments were not significantly different (p>0.05).
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Glasmacher, Axel, Corinna Hahn, Andrea Juttner, et al. "Chromosome Aberrations in 130 Patients with Multiple Myeloma Detected by Interphase FISH and Their Diagnostic and Prognostic Relevance." Blood 104, no. 11 (2004): 4938. http://dx.doi.org/10.1182/blood.v104.11.4938.4938.
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Abstract Recent publications have shown that chromosomal abnormalities in patients with leukemias play an important role with respect to therapy and prognosis. In multiple myeloma (MM) the role of specific cytogenetic changes relevant for the prognosis is still to be defined. Recent data suggest that much more patients show chromosomal aberrations than previously suspected, but differentiation between main and side lines of karyotype evolution was problematic. In the present investigation, cytogenetic analysis was performed using interphase FISH in 130 patients with multiple myeloma. For hybridization, 9 repetitive (chromosomes 3, 7, 9, 11, 15, 17, 18, X, Y) and 7 single copy probes (2x5, 13, 17, 21, 2x22) were used. Aberrations were detected in 87% of the patients. Most cases showed 1–3 aberrations. There was a correlation between the number of aberrations per patient and the tumor stage. E.g. the percentage of patients with 7–12 aberrations increased from 16% in stage II to 28% in stage III. Gains and losses of chromosomes showed significant interchromosomal differences with gains being more frequent than losses. Chromosomes 3, 5, 7, 9, 21 and 22 showed predominantly gains. Losses were found in chromsomes 13, 17, X and Y. But monosomy of sex chromosomes (average age of 63.5 years) may be in part explained by the age of the patients. For chromosomes 15 and 18 a similar number of monosomies and trisomies was found which might be caused by mitotic nondisjunction. Deletions 13q14 (28%), gain of 11q13 and translocation of IgH locus 14q32 (79%) are specific aberrations detected in 39 patients analysed with specific DNA probes of the relevant loci. All three aberrations led to modified survival times of the patients. Summarizing our results in 130 patients with MM, we found that the number of numerical chromosomal aberrations as well as selected structural aberrations proved to be of diagnostic and prognostic relevance.
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Reimann-Berg, N., J. Bullerdiek, H. Escobar, and I. Nolte. "Chromosome analyses in dogs." Tierärztliche Praxis Ausgabe K: Kleintiere / Heimtiere 40, no. 03 (2012): 191–96. http://dx.doi.org/10.1055/s-0038-1623638.
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SummaryCytogenetics is the study of normal and abnormal chromosomes. Every species is characterized by a given number of chromosomes that can be recognized by their specific shape. The chromosomes are arranged according to standard classification schemes for the respective species. While pre-and postnatal chromosome analyses investigate the constitutional karyotype, tumor cytogenetics is focused on the detection of clonal acquired, tumor-associated chromosome aberrations. Cytogenetic investigations in dogs are of great value especially for breeders dealing with fertility problems within their pedigrees, for veterinarians and last but not least for the dog owners. Dogs and humans share a variety of genetic diseases, including cancer. Thus, the dog has become an increasingly important model for genetic diseases. However, cytogenetic analyses of canine cells are complicated by the complex karyotype of the dog. Only just 15 years ago, a standard classification scheme for the complete canine karyotype was established. For chromosome analyses of canine cells the same steps of chromosome preparation are used as in human cytogenetics.There are few reports about cytogenetic changes in non-neoplastic cells, involving predominantly the sex chromosomes. Cytogenetic analyses of different entities of canine tumors revealed that, comparable to human tumors, tumors of the dog are often characterized by clonal chromosome aberrations, which might be used as diagnostic and prognostic markers. The integration of modern techniques (molecular genetic approaches, adaptive computer programs) will facilitate and complete conventional cytogenetic studies. However, conventional cytogenetics is still non-replaceable.
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Pérez-Simón, J. A., R. Garcı́a-Sanz, M. D. Tabernero, et al. "Prognostic Value of Numerical Chromosome Aberrations in Multiple Myeloma: A FISH Analysis of 15 Different Chromosomes." Blood 91, no. 9 (1998): 3366–71. http://dx.doi.org/10.1182/blood.v91.9.3366.3366_3366_3371.
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Recent observations indicate that chromosome aberrations are important prognostic factors in patients with multiple myeloma (MM) treated with high-dose chemotherapy. Nevertheless, the inherent problems of conventional cytogenetics have hampered the systematic evaluation of this parameter in series of patients treated with conventional chemotherapy. Fluorescence in situ hybridization (FISH) analysis is an attractive alternative for evaluation of numerical chromosomal changes. In the present study, we analyze the relationship between aneuploidies of 15 different chromosomes assessed by FISH and prognosis in a series of 63 patients with MM treated with conventional chemotherapy. After a median follow-up of 61 months (range, 6 to 109), 49% of patients are still alive with a median survival of 33 months. The overall incidence of numerical chromosome abnormalities was 70%. This incidence significantly increased when seven or more chromosomes were analyzed (53 patients), reaching 81%. Trisomies of chromosomes 6, 9, and 17 were associated with prolonged survival (P = .033, P = .035, and P = .026, respectively); by contrast, overall survival (OS) was lower in cases with monosomy 13 (as assessed by deletion of Rb gene,P = .0012). From the clinical point of view, loss of Rb gene was associated with a poor performance status; low hemoglobin levels; high creatinine, C-reactive protein, and lactic dehydrogenase serum levels; high percentage of bone marrow plasma cells (BMPC); extensive bone lytic lesions; and advanced clinical stage. Other chromosome abnormalities such as trisomy of chromosome 9 and 17 were associated with good prognostic features including high hemoglobin levels, early clinical stage, β2microglobulin less than 6 μg/mL, and low percentage of BMPC. A multivariate analysis for OS showed that S-phase PC greater than 3% (P = .010) and β2microglobulin serum levels greater than 6 μg/mL (P = .024), together with monosomy of chromosome 13 (P = .031) and nontrisomy of chromosome 6 (P = .048) was the best combination of independent parameters for predicting survival in patients with MM. According to these results, chromosomal analysis is of great use in patients with MM at diagnosis to have a correct prognostic evaluation for clinical decision making.
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Yahaya, Muhammad Sanusi, Mohd Shahrom Salisi, Nur Mahiza Md Isa, Goh Yong Meng, and Abdwahid Haron. "Prevalence of chromosome anomalies in a deer farm with fertility decline in Malaysia." Future Science OA 6, no. 6 (2020): FSO580. http://dx.doi.org/10.2144/fsoa-2020-0037.
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Background: A number of factors are known to reduce fertility rate in animals and one of the important categories of such factors is chromosome anomalies. They can occur with or without causing phenotypic abnormalities on animals; in some cases, they may directly affect meiosis, gametogenesis and the viability of conceptus. In many instances, balanced structural rearrangements can be transmitted to offspring, affecting fertility in subsequent generations. Aim: This work investigated the occurrence of chromosome aberrations in Rusa timorensis, Rusa unicolor and Axis axis raised in a nucleus deer farm in Malaysia with a history of declining fertility of unknown origin. Materials & methods: Blood samples were collected from 60 animals through venipuncture, cultured for 72 h and arrested at metaphase. SmartType® and Ideokar® software were used to karyotype the chromosomes. Results: We found 15 out of the 60 animals screened from both sexes harbor some form of chromosome aberration. Chromosomal aberrations exist at the rate of 25% and may not be unconnected with the observed reduced fertility on the farm. Further investigations should be carried out, especially on the offspring of the studied animals to transmission of these aberrations. The animals that are confirmed to transmit the chromosomal aberrations should be culled to arrest the propagation of their abnormalities.
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Pérez-Simón, J. A., R. Garcı́a-Sanz, M. D. Tabernero, et al. "Prognostic Value of Numerical Chromosome Aberrations in Multiple Myeloma: A FISH Analysis of 15 Different Chromosomes." Blood 91, no. 9 (1998): 3366–71. http://dx.doi.org/10.1182/blood.v91.9.3366.
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Abstract Recent observations indicate that chromosome aberrations are important prognostic factors in patients with multiple myeloma (MM) treated with high-dose chemotherapy. Nevertheless, the inherent problems of conventional cytogenetics have hampered the systematic evaluation of this parameter in series of patients treated with conventional chemotherapy. Fluorescence in situ hybridization (FISH) analysis is an attractive alternative for evaluation of numerical chromosomal changes. In the present study, we analyze the relationship between aneuploidies of 15 different chromosomes assessed by FISH and prognosis in a series of 63 patients with MM treated with conventional chemotherapy. After a median follow-up of 61 months (range, 6 to 109), 49% of patients are still alive with a median survival of 33 months. The overall incidence of numerical chromosome abnormalities was 70%. This incidence significantly increased when seven or more chromosomes were analyzed (53 patients), reaching 81%. Trisomies of chromosomes 6, 9, and 17 were associated with prolonged survival (P = .033, P = .035, and P = .026, respectively); by contrast, overall survival (OS) was lower in cases with monosomy 13 (as assessed by deletion of Rb gene,P = .0012). From the clinical point of view, loss of Rb gene was associated with a poor performance status; low hemoglobin levels; high creatinine, C-reactive protein, and lactic dehydrogenase serum levels; high percentage of bone marrow plasma cells (BMPC); extensive bone lytic lesions; and advanced clinical stage. Other chromosome abnormalities such as trisomy of chromosome 9 and 17 were associated with good prognostic features including high hemoglobin levels, early clinical stage, β2microglobulin less than 6 μg/mL, and low percentage of BMPC. A multivariate analysis for OS showed that S-phase PC greater than 3% (P = .010) and β2microglobulin serum levels greater than 6 μg/mL (P = .024), together with monosomy of chromosome 13 (P = .031) and nontrisomy of chromosome 6 (P = .048) was the best combination of independent parameters for predicting survival in patients with MM. According to these results, chromosomal analysis is of great use in patients with MM at diagnosis to have a correct prognostic evaluation for clinical decision making.
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P.T., N. Bagatska, E. Mykhailova, et al. "Cytogenetic Characteristic the Patients of Both Sexes with Phobic-anxiety Disorders." European Psychiatry 41, S1 (2017): S306. http://dx.doi.org/10.1016/j.eurpsy.2017.02.200.
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Background and aimsAnxiety-phobic disorders are caused both by environmental and hereditary factors. The study was designed to determine the level of chromosomal aberrations in the peripheral blood lymphocytes (PBL) of children and adolescents of both sexes with phobic-anxiety disorders (PAD).Patients and methodsCytogenetic analysis was performed in 27 children and adolescents of both sexes with PAD, aged 9–15 years; the control group consisted of 50 healthy peers of both genders. Statistical analysis-Excel and SPSS statistics 17.0.ResultsCytogenetic analysis of patients with PAD and in healthy age-matched individuals has established normal female (46,XX) and male (46,XY) karyotypes. The frequency of the chromosomal aberrations (CA) spontaneous level in the PBL is 4.6 times higher than the CA frequency in healthy persons. In children and adolescents with the disease, the spontaneous frequency of aberrations of chromatid and chromosome types is also significantly higher than the same in healthy children and adolescents. Single acentric fragments and exchanges prevail among the chromatid–type aberrations; pair acentric fragments prevail among the chromosome–type aberrations. An increase in the frequency of the chromosome-type aberrations has been revealed in boys with PAD (1.72 vs.0.55 per100 cells in healthy boys, P < 0.001 by pair acentric fragments), in comparison with healthy boys; and the chromatid–type aberrations have been observed in girls with PAD (3.22 vs.0.94 per 100 cells in healthy girls, P < 0.001 by single acentric fragments), in comparison with healthy girls. A pronounced individual variability of CA frequency, which ranges in our patients from 2.0 to18.0 per 100 metaphase plates, has been found along with an increase in the CA level in patients with PAD.ConclusionChildren and adolescents with PAD require a careful cytogenetic analysis and the consequent therapeutic measures for genome stabilization.Disclosure of interestThe authors have not supplied their declaration of competing interest.
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Cimino, G., F. Lo Coco, A. Biondi, et al. "ALL-1 gene at chromosome 11q23 is consistently altered in acute leukemia of early infancy." Blood 82, no. 2 (1993): 544–46. http://dx.doi.org/10.1182/blood.v82.2.544.544.
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Abstract Early infancy (< 1 year of age), massive tumor cell burden, and extremely poor prognosis are characteristic features of a particular subset of childhood acute leukemias (AL). In these cases, chromosome aberrations at the 11q23 band are the most frequently reported cytogenetic abnormalities. We have recently cloned a genetic locus named ALL-1, in which DNA breakpoints are clustered in leukemic patients with 11q23 aberrations. Analysis of the ALL-1 genomic configuration in DNA from 15 infants with AL showed specific ALL-1 rearrangements in 12 cases (80%), including 5 with normal karyotypes. These findings indicate that a consistent genetic defect underlies this particular leukemic subset.
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Cimino, G., F. Lo Coco, A. Biondi, et al. "ALL-1 gene at chromosome 11q23 is consistently altered in acute leukemia of early infancy." Blood 82, no. 2 (1993): 544–46. http://dx.doi.org/10.1182/blood.v82.2.544.bloodjournal822544.
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Early infancy (< 1 year of age), massive tumor cell burden, and extremely poor prognosis are characteristic features of a particular subset of childhood acute leukemias (AL). In these cases, chromosome aberrations at the 11q23 band are the most frequently reported cytogenetic abnormalities. We have recently cloned a genetic locus named ALL-1, in which DNA breakpoints are clustered in leukemic patients with 11q23 aberrations. Analysis of the ALL-1 genomic configuration in DNA from 15 infants with AL showed specific ALL-1 rearrangements in 12 cases (80%), including 5 with normal karyotypes. These findings indicate that a consistent genetic defect underlies this particular leukemic subset.
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Mušák, Ludovít, Veronika Poláková, Erika Halašová, et al. "Effect of occupational exposure to cytostatics and nucleotide excision repair polymorphism on chromosomal aberrations frequency." Interdisciplinary Toxicology 2, no. 1 (2009): 13–17. http://dx.doi.org/10.2478/v10102-009-0002-6.
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Effect of occupational exposure to cytostatics and nucleotide excision repair polymorphism on chromosomal aberrations frequencyAuthors evaluated the incidence of total chromosomal aberrations (CA) and their types - chromatid-type (CTA) and chromosome-type (CSA) in peripheral blood lymphocytes from 72 oncologic unit's workers occupationally exposed to cytostatics in relationship to polymorphisms of DNA repair genesXPD, XPGandXPC. The cytogenetic analysis was used for determination of chromosomal aberrations frequency and PCR-RFLP method for polymorphisms of genes. Statistically higher frequency of total CA was detected in exposed group as compared to control (1.90±1.34% vs. 1.26±0.93%; Mann-Whitney U-test,p=0.001). There was not detected any difference between CTA and CSA (0.92±1.04% vs. 0.98±1.17%). Similarly, in genesXPDexon 23 andXPCexon 15 wasn't detected any difference neither in total chromosomal aberrations nor in CTA and CSA types. Statistically significant decrease of total chromosomal aberrations and CTA-type with presence of variant allele C was detected in geneXPGexon 15. Authors pointed out the importance of individual susceptibility factors in evaluation of effects of genotoxic agents, in that event, when the concentration does not meet the occupational exposure limit.
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Shkarupa, V. M., and S. V. Klymenko. "RADIOPROTECTIVE PROPERTIES OF SODIUM HUMATE IN RADIATION-INDUCED MUTAGENESIS IN CULTURED LYMPHOCYTES OF THYROID CANCER PATIENTS." Experimental Oncology 38, no. 2 (2016): 108–11. http://dx.doi.org/10.31768/2312-8852.2016.38(2):108-111.
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Aim: To investigate the effect of sodium humate on the level of cytogenetic damage in culture of lymphocytes of patients with thyroid cancer after γ-irradiation. Materials and Methods: Metaphase analysis of chromosome aberrations in cultured peripheral blood lymphocytes of 10 individuals with thyroid cancer was performed after irradiation of lymphocytes in vitro at a dose of 1 Gy from 137Cs source at the early G0 phase of cell cycle. Sodium humate was added to cell culture for 30 ± 15 min after phytohemagglutinin stimulation at concentrations of 10 and 100 μg/ml. Results: Sodium humate exhibited antimutagenic properties. The preparation at a concentration of 10 μg/ml was more effective than at a concentration of 100 μg/ml, reducing the average incidence of radiation-induced chromosome aberrations by 51.88 and 38.77%, respectively. The most pronounced antimutagenic effect of sodium humate was the reduction of the frequency of chromosomal type aberrations, however, such efficiency varied between individual patients with thyroid cancer. Conclusions: Sodium humate could be considered as a potential therapeutic modifier of radiation damage.
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Sawyer, Jeffrey, Erming Tian, Christoph Heuck, et al. "Hyperhaploid Multiple Myeloma (MM): A Rare Karyotypic Subgroup Retaining Disomy 18 and 1q12∼23 Amplification." Blood 120, no. 21 (2012): 3983. http://dx.doi.org/10.1182/blood.v120.21.3983.3983.
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Abstract Abstract 3983 In MM, chromosome ploidy levels are commonly used in the cytogenetic risk stratification of the disease. Two distinct ploidy groups occur: a hyperdiploid group, associated with a better prognosis, and a hypodiploid group, associated with a poor prognosis. The hyperdiploid group (47–57 chromosomes) is characterized by a consistent set of odd-numbered chromosomes including trisomies for chromosomes 3,5,7,9,11,15,19, and 21. This group is also characterized by fewer structural aberrations and is found in 50% to 60% of patients with metaphase aberrations. The hypodiploid group (35–45 chromosomes) encompasses clones composed of either hypodiploid, pseudodiploid, and/or near-tetraploid variants. The hypodiploid group has more frequent structural chromosome aberrations involving adverse IGH translocations and deletions of 17p. We have identified a group of 22 patients by routine G-banding with hyperhaploid karyotypes that exhibit a range of 30–34 chromosomes with a modal number of 32. The hyperhaploid clones are characterized by the same set of odd-numbered chromosomes found in hyperdiploid MM, including 3, 5, 7, 9, 11, 15, 19, and 21, however all these chromosomes are found in disomy instead of trisomy. The single notable exception is the retention of chromosome 18 in the hyperhaploid karyotypes. In seventeen of the 22 patients, both a hyperdiploid clone and a hyperhaploid clone were identified in the same sample, with the hyperdiploid clone always representing the dominant cell line. Five patients showed only a hyperhaploid clone. Importantly, both the hyperdiploid and hyperhaploid clones in these patients shared the same set of structural aberrations. This suggests the hyperhaploid karyotypes originated from the hyperdiploid clones by the loss of a single normal copy of each chromosome pair. Chromosome 18 was retained in 18 of 22 patients, and all or part of 1q was retained or newly amplified in five patients. Ten of 22 patients also exhibited the loss or deletion of chromosome 5, which indicates this is an additional secondary event in the hyperhaploid clones. Additionally, we investigated the hyperhaploid clones utilizing fluorescence in-situ hybridization (FISH) and spectral karyotyping in the nine samples that adequate sample was available. FISH probes for IGH rearrangements indicated that only two of the nine cases had IGH translocations, one with a t(4;14), while in the other case a receptor of the IGH signal was not identified. Deletions of 17p (TP53) were found in all nine samples. FISH for 1q21 (CKS1B) was informative in five cases and showed a 1q copy number (CN) of 2 in three cases, of 3 in one case, and of 2–6 in one case. The only recurring structural aberrations identified in the hyperhaploid clones were aberrations of 1q. Segmental disomy for 1q12∼23 was retained in the sole chromosome 1 in two patients (cryptic to G-banding), and whole-arm jumping 1q (JT1q12) was identified in 2 cases. One particularly informative case with a JT1q21 demonstrated a CN of 2–6 for 1q21 and instability of the 1q12 pericentromeric heterochromatin in the form of triradials of 1q. The multi-radials of 1q were the origin of multiple extra acentric copies of 1q and acentric isochromosomes 1q. The findings in this study indicate that a progression of chromosome aberrations exists in hyperhaploid MM just as it does in hyperdiploid and hypodiploid MM. The hyperhaploid clones apparently originate from a single catastrophic event in which an entire haploid set of chromosomes is lost from a hyperdiploid clone, with the striking exception of the retention of chromosome 18. In patients with structural chromosome aberrations, the same set of aberrations is retained in the hyperhaploid cells, including 1q12∼23 amplification. In a subset of patients, these clones may then undergo a loss or deletion of chromosome 5. Finally, hyperhaploid clones can also undergo genomic instability in the form of JT1q12 translocations involving whole-arm CN increases of 1q. The retention of disomy for only chromosome 18 and 1q12∼23 amplification suggests these two specific chromosome aberrations may be important in the survival of these clones. In this group of 22 patients, the median survival time from diagnosis was 32 months, suggesting a poor prognosis for hyperhaploid MM. Disclosures: No relevant conflicts of interest to declare.
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Bagger, Mette, Morten T. Andersen, Steffen Heegaard, Mette K. Andersen, and Jens F. Kiilgaard. "Transvitreal Retinochoroidal Biopsy Provides a Representative Sample From Choroidal Melanoma for Detection of Chromosome 3 Aberrations." Investigative Opthalmology & Visual Science 56, no. 10 (2015): 5917. http://dx.doi.org/10.1167/iovs.15-17349.
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Vajen, Beate, Kathrin Thomay, Winfried Hofmann, Brigitte Schlegelberger, and Gudrun Göhring. "Numerical Aberrations Involving The X Chromosome As a New Recurrent Aberration In Patients With Chronic Lymphocytic Leukemia." Blood 122, no. 21 (2013): 4880. http://dx.doi.org/10.1182/blood.v122.21.4880.4880.
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Abstract Genomic aberrations in CLL are important independent predictors of disease progression and survival in chronic lymphocytic leukemia (CLL). The most frequent changes are a deletion in 13q with a median survival of 133 months, a deletion in 11q (median survival 79 months), trisomy of chromosome 12 (114 months) and a deletion in 17p (32 months) (Döhner et al., NEJM, 2000; Hallek et al., Lancet, 2010). Between 2001 and 2012 we performed cytogenetic analyses of 2360 patients with CLL. We detected clonal chromosome aberrations in 1298/2360 (55%). Besides typical recurrent aberrations associated with CLL, we observed in 72/2360 (3%) clonal numerical aberrations involving the X chromosome. In 50/72 patients (69%) a loss of chromosome X and in 22/72 patients (31%) a gain of an X chromosome was detected. So far, numerical alterations of the X chromosome have not been described as recurrent aberrations detected in CLL. In order to understand their significance, we analysed those cases in greater detail. Median age of patients was 69 years (33-89 years) and the sex distribution was 64 female and 8 male (ratio 8:1). The patient cohort with the loss of the X chromosome consisted of 48 female and two male patients between 35 and 89 years of age (median age 69 years). In 52% (26/50) loss of chromosome X was detected as a sole abnormality and 22% (11/50) showed the loss of X within a complex karyotype. There was an association between loss of the X chromosome and trisomy 12 in 10% (5/50) and with deletion in 13q in 22% (11/50). In two cases, a clonal evolution was observed with the loss of the X chromosome in the main clone. Four independent clones (8%) were identified, three with trisomy 12 (6%) and one with a deletion in 11q (2%). Further, we analysed cases with a gain of the X chromosome (22 patients with CLL (16 female,6 male) between 33 and 81 years of age (median age 63 years)). In 15/22 patients (68%) a gain of the X chromosome was identified as a sole abnormality and in 6 of 22 within a complex aberrant karyotype. In 3/22 patients (14%) with an isolated gain of the X chromosome, we detected an independent clone. The independent clone was a trisomy 12 (two patients) and a monosomy X (one patient). In two cases, a clonal evolution was identified with gain of chromosome X in the subclone as a secondary event. Interestingly, the clone size was rather small. The median size of clones with loss of the X chromosome was 6/20 metaphases (30%) and with gain of the X chromosome was 4/20 metaphases (20%). In 8 patients, a loss of chromosome X could be detected in two metaphases only or a gain in one metaphase only, not fulfilling the criteria for clonality. In these cases, fluorescence in situ hybridization never confirmed the presence of a clone with X chromosome abnormalities. Even though a monosomy X has been reported as a recurrent somatic sole abnormality in MDS, it is not a characteristic aberration specific for any subtype of leukemia, lymphoma or a solid tumor (Abruzzese et al., Cancer Genet Cytogenet, 1997). The constitutional loss of the X chromosome is associated with Turner syndrome, a genetic disorder affecting 1/2500-3000 live-born. Notably, in a mosaic Turner syndrome patient with CLL, abnormal clones were restricted to the monosomic cells, indicating that loss of the X chromosome provides an advantage for leukemia cells (Manola et al., Leuk Res., 2008). However, CLL is not associated with Turner syndrome. A gain of chromosome X was observed by Aamot et al. (J Cancer Res Clin Oncol., 2007) in 17% of patients with follicular lymphomas as a secondary aberration with the characteristic translocation t(14;18) not affecting the overall survival. This is in accordance with our findings that a gain of the X chromosome could be a characteristic aberration in lymphatic neoplasms. Since we detected the aberrations involving chromosome X mostly in CLL, a constitutional mosaicism is unlikely. Otherwise, a constitutional mosaic would possibly be a predisposing factor for CLL. Putative candidate genes on chromosome X are not known. BRWD3, located on Xq13, encodes a bromodomain and WD repeat domain-containing protein and could be a putative novel transcription factor, since it is involved in translocations and is slightly down-regulated in CLL patients (Kalla et al., Genes Chromosomes Cancer, 2005). In summary, we identified numerical aberrations of the X chromosomes as new recurrent aberrations in CLL. The impact is still unknown and has to be analysed in further studies. Disclosures: No relevant conflicts of interest to declare.
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Heerema, Nyla A., Gerard Lozanski, Thomas S. Lin, Molly Moran, Michael R. Grever, and John C. Byrd. "Cytogenetic Studies of 539 Chronic Lymphocytic Leukemia (CLL) Patients." Blood 106, no. 11 (2005): 1192. http://dx.doi.org/10.1182/blood.v106.11.1192.1192.
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Abstract Previous banded metaphase cytogenetic studies of CLL identified deletions of 13q, 11q, 17p and 6q and trisomy 12 as recurring aberrations; all except del(6q) have well-recognized prognostic significance. The association of other cytogenetic abnormalities with these recurring aberrations has not been previously described. To more completely characterize our patients with CLL, we performed banded metaphase cytogenetics and fluorescence in situ hybridization (FISH) on 539 patients with previously untreated as well as relapsed CLL. By banded metaphase analysis 236 cases were abnormal, 282 were normal (≥20 metaphases and no abnormal clone identified) and 21 were culture failures. Of the 236 abnormal cases, 30 had a sole numerical sex chromosome abnormality, which may not represent the malignant clone. 89 cases had complex karyotypes (≥ 3 unrelated abnormalities), and 147 had simple abnormalities. Losses (451 total, 116 whole chromosome, 47 of which were sex chromosomes, and 335 partial losses) were much more common than gains (132 total, 110 whole chromosome, 68 +12, 13 +X or Y, only 29 other whole chromosome gains, and 22 partial chromosome gains). 130 balanced rearrangements occurred; most frequently involving chromosomes 14 and 1 (15 and 14 balanced rearrangements, respectively). As previously reported, +12, del(13q), del(11q), del(17p) and del(6q) occurred frequently (34.3%, 14.4%, 16.5%, 22.9%, and 10.2% of cases, respectively). Other frequent losses involved 14q, 9p, 3p and 18p (8.5%, 6.8%, 6.4% and 5.9% of cases, respectively). Partial chromosome losses usually resulted from apparent unbalanced translocations, suggesting frequent non-reciprocal interchromosomal rearrangements that may represent a unique form of chromosomal instability. We recently have begun examining the clinical significance of secondary abnormalities occurring with common aberrations in CLL. Of interest, all patients with t(14;18)(q32;q21) and 7 of 10 patients with trisomy 18 also had trisomy 12. All 4 patients with t(14;18) CLL had atypical immunophenotypes with only one developing symptomatic disease requiring therapy. A similar atypical immunophentype was found in 5 of 7 pts with co-existent trisomy 12 and 18, and only one of these patients has progressed to require treatment. In contrast, 36 of the remaining 57 pts with trisomy 12 have developed progressive disease requiring therapy. Overall, our studies show that multiple chromosomal aberrations in addition to those commonly reported occur in CLL. Chromosomal losses are more common than gains, and unbalanced rearrangements are more frequent than balanced rearrangements. The unbalanced rearrangements are frequently interchromosomal and may indicate a unique type of chromosomal instability. Unlike the other common cytogenetic aberrations in CLL, trisomy 12 appears to be associated with secondary aberrations including t(14;18) and trisomy 18 that may define a different more favorable clinical pathologic history than observed in trisomy 12 patients without these secondary aberrations.
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Barragan, Carlo Sergio, Silvia B. Hansson, Silvina A. Cicchini, et al. "Multiple Myeloma, Detection of Four Unfavorable Genetic Pronostic Factor by Interphase Two-Color Fluorescence in Situ Hybridization Analyses: A Study of 33 Patients At Diagnosis or Relapse." Blood 120, no. 21 (2012): 5004. http://dx.doi.org/10.1182/blood.v120.21.5004.5004.
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Abstract Abstract 5004 Background: Interphase Fluorescence in situ hybridization (FISH) has improved the detection of early bad prognostic genomic aberrations in Myeloma (MM) is a fast and reliable method. We used this assay in myeloma patients at diagnosis, after relapse or treatment failure. Methods: Interphase Mononuclear cells from Bone Marrow of 36 Caucasian patients, 13 men and 23 women, age ranged from 40 to 84 years (median, 64) with MM. were analyzed by LEXEL Live FISH probes, for deletions in chromosome band 13q14. 3, 17p13. 1; IGH/CCND1 translocation dual fusion and cMYC breakapart 8 Chromosome. Results: Chromosomal aberrations were detected in 16 of 33 evaluable patient samples of a total 36 patients population. The most frequent aberrations were 7/16 in 13p14. 3 band deletion (43. 75%) 7/33 (21%); 5/16 (31, 25%)patients with deletion had 17p13. 15/33 (15, 15%); 3 cMYC breakapart 3/16 (18. 75%) 3/33 (9%); IGH/CCND1 translocation in 3 patients 3/16 (18. 75%) 3/33 (9%), two of them associated one with cMYC and the other with 13p14. 3. We found other association: A)13p14. 3; 17p13. 1 and cMYC in (1/33). B) 13p14. 3 and cMYC (1/33) C) 17p13. 1; cMYC (1/33). Two patients had 8 chromosome trisomy 2/33 (6%). We foun that 13p14. 3, 17p13. 1 and cMYC association was correlated with a worst and fast evolution. Who had 13p14. 3 band deletion had a worst evolution in our patients. cMyc was associated with a poor prognosis. Conclusions: Genomic aberrations are independent prognosis factors of disease progression, chemotherapy respond and survival in Myeloma. Novel DNA molecular target and bone marrow micro environment modification drugs such as bortezomib and thalidomide or lenalidomide must be use in first line associated perhaps with standar chemotherapy drugs for improving result and consolidate this patients with autologous bone marrow transplantation avoiding the dilate of this strategic in patient with poor prognosis. Future trials must be performed to include a more complete panel of probes in Myeloma. Disclosures: No relevant conflicts of interest to declare.
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Liyanage, Marek, Zoë Weaver, Carrolee Barlow та ін. "Abnormal rearrangement within the α/δ T-cell receptor locus in lymphomas from Atm-deficient mice". Blood 96, № 5 (2000): 1940–46. http://dx.doi.org/10.1182/blood.v96.5.1940.
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Abstract Atm-deficient mice (Atm−/−) recapitulate many aspects of the ataxia telangiectasia (AT) syndrome, including the susceptibility to tumors of lymphoid origin. To investigate the mechanism of tumorigenesis, we have examined a panel of 8 thymic lymphomas from Atm−/− mice. AllAtm−/− tumors are of thymic lymphoblastoid origin, display an immature CD3− and CD4+/CD8+ phenotype, and arise coincident with V(D)J recombination. Cytogenetically, all tumors are diploid or near diploid but exhibit multiple chromosome aberrations with an average of 4 abnormal chromosomes per tumor. All the tumors revealed chromosome 14 rearrangements precisely at the T-cell receptorα/δ(Tcrα/δ) locus, suggesting the involvement of V(D)J recombination in these translocations. In addition, 11.5% ofAtm−/− peripheral T cells showed chromosome 14 translocations, suggesting that rearrangements at theTcrα/δ locus occur early during tumor development in the absence of ATM. However, additional genetic aberrations are required for tumorigenesis. For example, translocations involving chromosome 12, often with chromosome 14 (more than 60%), and partial or complete trisomy of chromosome 15, with copy number increases of the c-myc oncogene were frequently observed. These observations suggest that ATM is required for normal rearrangement of the Tcrα/δ locus but not for V(D)J recombination at other loci. The mechanisms that lead to tumorigenesis may be due to the involvement of ATM in monitoring double-stranded DNA breaks.
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Liyanage, Marek, Zoë Weaver, Carrolee Barlow та ін. "Abnormal rearrangement within the α/δ T-cell receptor locus in lymphomas from Atm-deficient mice". Blood 96, № 5 (2000): 1940–46. http://dx.doi.org/10.1182/blood.v96.5.1940.h8001940_1940_1946.
Full textAbstract:
Atm-deficient mice (Atm−/−) recapitulate many aspects of the ataxia telangiectasia (AT) syndrome, including the susceptibility to tumors of lymphoid origin. To investigate the mechanism of tumorigenesis, we have examined a panel of 8 thymic lymphomas from Atm−/− mice. AllAtm−/− tumors are of thymic lymphoblastoid origin, display an immature CD3− and CD4+/CD8+ phenotype, and arise coincident with V(D)J recombination. Cytogenetically, all tumors are diploid or near diploid but exhibit multiple chromosome aberrations with an average of 4 abnormal chromosomes per tumor. All the tumors revealed chromosome 14 rearrangements precisely at the T-cell receptorα/δ(Tcrα/δ) locus, suggesting the involvement of V(D)J recombination in these translocations. In addition, 11.5% ofAtm−/− peripheral T cells showed chromosome 14 translocations, suggesting that rearrangements at theTcrα/δ locus occur early during tumor development in the absence of ATM. However, additional genetic aberrations are required for tumorigenesis. For example, translocations involving chromosome 12, often with chromosome 14 (more than 60%), and partial or complete trisomy of chromosome 15, with copy number increases of the c-myc oncogene were frequently observed. These observations suggest that ATM is required for normal rearrangement of the Tcrα/δ locus but not for V(D)J recombination at other loci. The mechanisms that lead to tumorigenesis may be due to the involvement of ATM in monitoring double-stranded DNA breaks.
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Viardot, Andreas, Carsten Schwanen, Nicola Goekbuget, et al. "Identification of Novel Recurrent Genomic Aberrations by Array-CGH in Adult Acute Lymphoblastic Leukemia." Blood 108, no. 11 (2006): 4476. http://dx.doi.org/10.1182/blood.v108.11.4476.4476.
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Abstract In acute lymphoblastic leukaemia (ALL), genomic aberrations like translocations t(4;11) or t(9;22) are associated with an adverse prognostic impact and play an important role in the development of risk adapted treatment strategies. So far, chromosomal banding analysis is the standard cytogenetic procedure for routine diagnosis. Genomic array-comparative genomic hybridization (aCGH) has become a useful technique for genomic screening allowing a more precise delineation of small genomic aberrations. We analyzed 44 patients with ALL, which were treated within the GMALL trials, by aCGH analysis using a genomic 2,8K chip. In 27 patients, clinical data were available. Thirteen patients had a common-ALL with normal karyotype, 10 patients had a common-ALL/Pr-B-ALL with t(9;22), two patients had either pre-B-ALL or T-lineage leukaemia, respectively. Ten patients were classified as very high risk (t(9;22) positive), 2 patient as high-risk (pre-T-ALL; c-ALL with high leukocytes) and 15 patients were standard risk according to the risk stratification of the GMALL-studies. We found genomic aberrations in 30 out of 44 patients (68%). The most frequent aberrations were deletions on chromosome band 9p21 (10 cases; 23%), deletions on chromosome band 7q35 (7 cases; 16%); gains on chromosome X and losses on 7p (6 cases; 14% each), deletions on 13q14 (5 cases; 11%) and gains on 8q24 (4 cases; 9%). The consensus region of the 9p21 deletion was narrowed down to a size of 420 kilobasepairs. This region covers 3 different genes with potential tumor suppressor gene (TSG) function: p14ARF, p15INK4B/p10 and p16INK4A. An additional TSG gene - methylthioadenosine phosphorylase (MTAP) - was found in 9 out of these 10 cases. In 3 cases with 9p21 deletions, none of the patients expressed the p16INK4A protein using western blot analysis. Two patients where also negative for the MTAP protein, whereas another patient whithout a genomic deletion on MTAP remains positive. There was a tendency to a higher number of aberrations per case in the standard risk group in contrast to the t(9;22) positive group (2.1 vs. 1.0 aberrations per case). aCGH analysis is useful for the identification of recurrent genomic aberrations which are not detectable using standard cytogenetic techniques.
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Gohring, Gudrun, Kyra Michalova, Berna Beverloo, et al. "A Complex Karyotype but Not Monosomy 7 Is an Independent Prognostic Factor in Advanced Childhood MDS." Blood 110, no. 11 (2007): 2452. http://dx.doi.org/10.1182/blood.v110.11.2452.2452.
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Abstract Disclosure: No relevant conflicts of interest to declare. To study the clinical significance of recurrent chromosome aberrations in childhood MDS, cytogenetic data of 394 consecutive children with refractory cytopenia (RC) (N=215), RAEB (N=141) and RAEB-T (N=38) analyzed in the regional cytogenetic reference centers and registered in the prospective study EWOG-MDS 98 between 1998 and 2005 were evaluated. At diagnosis, a karyotype could be defined in 279/394 patients (pts) (71%). No karyotype was obtained in 16% of pts with RC compared to 8% pts with RAEB and RAEB-t (p<0.001). Clonal chromosome aberrations were more common in pts with advanced MDS (RAEB and RAEB-T, 61%) compared to RC (29%), and in pts with secondary (69%) compared to primary MDS (36%) (p<0.001). Monosomy 7 was the most frequent aberration occurring with similar frequency in RC (47% of abnormal karyotypes) compared to advanced MDS (49%) and in primary (53%) compared to secondary (41%) MDS. In addition, aberrations typical for de novo AML such as aberrations involving 11q23 or 3q, t(6;9) and del(9q) were noted in morphologically and clinically unequivocal MDS cases. Recurrent aberrations of adult MDS like isolated del(5q), del(20q) and -Y were very uncommon indicating a different pathogenesis of these cases. In pts with advanced MDS, there was no significant difference in overall survival (OS) of pts with normal karyotype (44% ± 18) compared to pts with monosomy 7 (58% ± 19) and patients with other karyotypes (61% ± 22). However, pts with advanced MDS and a complex karyotype (defined by ≥ 3 chromosome aberrations, presence of structural aberrations and excluding clonal evolution of monosomy 7) had a shorter OS (16% ±15, p<0.01). OS and event-free survival after hematopoietic stem cell transplantation (HSCT) in pts with complex karyotypes was inferior compared to that of pts with other cytogenetic aberrations (p=0.012 and 0.039, respectively). Within the group of pts with secondary MDS, complex karyotypes were found in MDS evolving from inherited bone marrow failure disorders or after radio-/ chemotherapy, but absent in familial MDS and cases evolving from acquired aplastic anemia. As shown in a multivariate Cox analysis, advanced MDS, secondary MDS, the presence of a complex karyotype and HSCT were identified as independent prognostic factors for OS. Thus, this study demonstrates the prognostic significance of cytogenetic findings in advanced childhood MDS independent of HSCT.
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Metzger, Andrew K., Gayatry Mohapatra, Yuriko A. Minn, et al. "Multiple genetic aberrations including evidence of chromosome 11q13 rearrangement detected in pituitary adenomas by comparative genomic hybridization." Journal of Neurosurgery 90, no. 2 (1999): 306–14. http://dx.doi.org/10.3171/jns.1999.90.2.0306.
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Object. This study was conducted to determine whether comparative genomic hybridization (CGH) is a more sensitive method for detecting genetic aberrations than other tests currently in use.Methods. The authors used CGH to examine 40 primary and 13 recurrent adenomas obtained from 52 patients for loss and gain of genetic material. Copy number aberrations (CNAs) were detected in 25 (48%) of the 52 patients studied. The chromosomes affected were, in order of decreasing frequency, 11, 7, X, 1, 8, 13, 5, 14, 2, 6, 9, 10, 12, 3, 18, 21, 4, 16, 15, 19, 22, and Y. Endocrinologically active adenomas were more likely to contain (p = 0.009) and had a greater number (p = 0.003) of CNAs. Of 26 adenomas with CNAs, 18 showed multiple aberrations involving entire chromosomes or chromosome arms. The most frequent CNA involving a chromosome subregion, which was present in four (8%) of 53 adenomas, was the loss of all chromosome 11 material except for a preserved common segment containing 11q13. Immunoperoxidase staining did not detect cyclin D1 expression in those four cases, making cyclin D1 an unlikely target of this rearrangement.Conclusions. These findings indicate that genetic abnormalities are present in pituitary adenomas at a higher rate than previously reported, are associated with endocrinological activity, and often involve several chromosomes. Rearrangement at 11q13 may inactivate a tumor suppressor gene or activate an oncogene that is important in the initiation or progression of sporadic pituitary adenomas.
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Veltman, Joris A., Fredrik J. Bot, Ference C. Huynen, Frans C. S. Ramaekers, Johannes J. Manni, and Anton H. N. Hopman. "Chromosome Instability as an Indicator of Malignant Progression in Laryngeal Mucosa." Journal of Clinical Oncology 18, no. 8 (2000): 1644–51. http://dx.doi.org/10.1200/jco.2000.18.8.1644.
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PURPOSE: Routine histologic examination cannot predict whether premalignant laryngeal lesions will progress toward invasive growth. The acquisition of changes in chromosome constitution has been suggested to be essential for driving tumor progression by enhancing mutagenic mechanisms. The aim of the present study was to determine whether chromosomal changes occur in the subsequent stages of early laryngeal carcinogenesis and, if so, whether these changes can be of prognostic value. MATERIALS AND METHODS: Numerical aberrations for chromosomes 1 and 7 were detected in tissue sections from archival material using an improved in situ hybridization protocol. In total, eight benign laryngeal lesions, 37 premalignant laryngeal lesions, and 16 specimens containing histologically normal epithelia adjacent to laryngeal squamous cell carcinomas were studied. Both the histologic and the cytogenetic classifications were correlated with progression to laryngeal cancer. RESULTS: No evidence for chromosome alterations was obtained in the control group, nor in histologically normal epithelia adjacent to laryngeal squamous cell carcinomas, nor in all but one hyperplastic lesion (n = 11). In contrast, 14 of 15 dysplastic lesions and nine of 11 carcinomas-in-situ contained numerical chromosomal aberrations. Tetrasomy was present in the majority of the dysplastic lesions. An unstable chromosome content (indicated by the presence of chromosome imbalances and/or polyploidization) in the premalignant lesion strongly predicted its malignant progression. CONCLUSION: Our results show that laryngeal tumor development involves chromosome tetraploidization. The further change from a stable to an unstable chromosome constitution is of importance for malignant progression.
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Michalova, Kyra, Zuzana Zemanova, Lenka Pavlistova, et al. "Molecular Cytogenetic Study of Immunofluorescently Labeled Plasma Cells and Prognostic Significance of Clonal Chromosomal Aberrations in Multiple Myeloma." Blood 108, no. 11 (2006): 5012. http://dx.doi.org/10.1182/blood.v108.11.5012.5012.
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Abstract Finding of clonal chromosomal aberrations in plasma cells is considered as one of the most important and independent prognostic factor in patients with multiple myeloma (MM). The most frequent and reliable cytogenetic indicators are chromosome 13q deletions (intermediate or moderately adverse prognosis), and translocations involving the immunoglobulin heavy chain gene (IgH) at 14q32 region. IgH gene is involved in translocations with different partner genes and these rearrangements are related to a very poor prognosis. The only exception is translocation t(11;14)(q13;q32) which is often connected with longer overall survival and therefore considered to be a favorable prognostic factor. The aim of the study was to assess the frequency of the most important chromosomal aberrations in immunofluorescently labeled plasma cells of patients with MM by interphase fluorescence in situ hybridization (I-FISH), and to evaluate their prognostic significance. During the last two years we examined 128 newly diagnosed patients with MM by conventional G-banding technique and by I-FISH. We focused on detection of aberrations of 13q, IgH gene rearrangements, and t(11;14)(q13;q32) translocation. I-FISH was done by locus-specific DNA probes (Abbott-Vysis, Des Plaines, Illinois, USA). Fifteen patients with complex karyotype were re-examined by multicolor FISH (mFISH, MetaSystems GmbH, Altlussheim, Germany). G-banding revealed abnormal karyotypes in 25% of patients, I-FISH detected chromosomal abberations in 82.8% cases. Abberations of chromosome 13 were found in plasma cells of 84 patients (65,6%), the incidence was: del(13)(q14) in 11%, monosomy 13 in 40%, combination of del(13)(q14)/monosomy 13 in 8%, and other aberrations of chromosome 13 in 7% of cases. Aberrations of IgH gene were proved in 82 patients (64%). t(11;14)(q13;q32) was seen in fourteen patients (11%) and other translocations affecting 14q32 region in 19 patients (15%). Besides translocations, different variations of total and/or partial deletions of IgH gene were detected in 28 cases (22%). In nine patients (7%) we found clones with translocation and deletion of 14q32 simultaneously, twelve patients (9%) had other IgH aberrations. Univariate statistical testing showed aberrations of 13q (p=0.042), and IgH gene rearrangments (translocations except t(11;14)(q13;q32) or deletions; p=0.007) to be associated with significantly shorter progression-free survival. The worst prognosis in our cohort was for 18 patients with combination of chromosome 13 anomalies together with rearrangements of IgH gene (p=0.049). Method of immunofluorescent labeling of plasma cells allows higher detection of chromosomal changes by I-FISH technique and therefore correct prognosis of the disease can be done.
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Nessipbayeva, Zhansaya, Minira Bulegenova, Meruert Karazhanova, and Dina Nurpisova. "Comparative analysis of chromosomal aberrations in children with acute leukemia." Journal "Medicine" 5-6, no. 215-216 (2020): 7–14. http://dx.doi.org/10.31082/1728-452x-2020-215-216-5-6-7-14.
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Leukemia is a hematopoetic tissue tumor with a primary lesion of the bone marrow, where the morphological substrate is the blast cell. Chromosomal and molecular genetic aberrations play a major role in the acute leukemia pathogenesis, determing the morphological, immunological and clinical features of the disease. Our study was aimed to to analyze retrospectively the structure and frequency of chromosomal aberrations in children with initially diagnosed acute leukemia. Material and methods. Medical histories retrospective analysis of children charged to oncohematology department of the «Scientific Center of Pediatrics and Pediatric Surgery» in Almaty for the period 2015 - 2017 was carried out. 310 histories with primary diagnosed acute leukemia were studied. Results and discussion. Among 310 patients different chromosome aberrations were isolated in 158 patients (51%) during cytogenetic and molecular cytogenetic (in situ hybridization) studies of bone marrow blast cells. A normal karyotype was observed in 102 patients (33%). Conclusion. The lymphoblastic variant of acute leukemia was determined in 75.5%, that indicates its leading role in AL structure among the children of different ages. AML was determined in 22.6% of all OL cases. The most frequent chromosomal rearrangement in ALL patients was blast cell chromosome hyperdiploidy (10,6%) and t(12;21)(p13;q22)/ETV6-RUNX1,which was detected in 37 (16%) patients. The most frequent AML abberation was t (8;21) (q22;q22)/RUNX1-RUNX1T1, identified in 15 (21.4%) patients. Keywords: acute leukemia, bone marrow, blast cells, karyotype, chromosomal aberrations, cytogenetic study.
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Hausmann, Michael, C. Paul Popescu, Jeannine Boscher, Dominique Kerboœf, Jürgen Dölle, and Christoph Cremer. "Identification and Cytogenetic Analysis of an Abnormal Pig Chromosome for Flow Cytometry and Sorting." Zeitschrift für Naturforschung C 48, no. 7-8 (1993): 645–53. http://dx.doi.org/10.1515/znc-1993-7-819.
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Abstract For cytogenetics of pig (Sus scrofa domestica) and the influence of chromosome aberrations on pig production, high interest exists in flow sorted chromosomes for gene mapping, to establish DNA-libraries, or to produce DNA-probes. Flow karyotyping and sorting as well as slit scan flow analysis of metaphase chromosomes of an abnormal cell type carrying a translocation marker chromosome 6/15 are described. Flow sorting of the largest chromosomes of these cells was performed. After sorting the chromosomes still had a well preserved morphology and were identified microscopically by G-banding. The quality of the band pattern of the sorted chromosomes was compatible to that of isolated chromosomes not subjected to flow cytometry. The sorted fraction showed an enrichment of chromosom e 6/15 and chromosome 1 which have quantitatively about the same integrated fluorescence intensity. Slit scan flow analysis was performed to discriminate these two chromosomes. Metacentric and submetacentric chromosom es were analyzed according to their bimodal slit scan profiles. Profiles of the largest chromosomes were distinguished by their different centromeric indices. Two groups were interpreted as the normal chromosome 1 and the translocation chromosom e 6/15.
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Göhring, Gudrun, Caroline Fedder, Kathrin Lange, et al. "Telomere Shortening and Chromosomal Instability in Chronic Lymphocytic Leukemia." Blood 118, no. 21 (2011): 1761. http://dx.doi.org/10.1182/blood.v118.21.1761.1761.
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Abstract Abstract 1761 Chronic lymphocytic leukemia (CLL) is a neoplastic disorder of B-lymphocytes, typically with a high number of peripheral B-lymphocytes and small mature lymphocytes (M Hallek et al, Ann Oncol. 16, Suppl 1:i50-1 (2005). Clinically, some patients have a mild, largely asymptomatic course of the disease and a normal life expectancy, while others suffer from fulminant progression and have a very short survival. An important predictive factor is the presence of typical chromosome aberrations (H Doehner et al, N Engl J Med343, 1910–1916 (2000)). Due to a low proliferative rate of the cells, the gold standard for cytogenetic diagnostics in CLL is fluorescence in situ hybridization (FISH). Therefore, not much is known about the incidence of complex karyotypes, although they are strong predictors of a very poor prognosis in CLL (C Mayr et al, Blood107, 742–751 (2007)). By stimulating the cells with different interleukins and CpG-oligodeoxynucleotides, we were able to detect complex karyotypes in about 10% of investigated cases of CLL by classical banding analysis. In this study, we characterized 24 patients with CLL and complex karyotype by performing multicolor fluorescence in situ hybridization (mFISH). Hereby, we could identify cryptic aberrations and describe the karyotype in greater detail. In addition to typical aberrations involving 6q, 11q, 13q and 17p and trisomy 12, (iso)dicentric chromosomes and whole-arm translocations of chromosomes Y, 1, 3, 4, 5, 13, 15, 17, 18, 21 and 22 were detected. These chromosome aberrations were mostly generated by breaks in heterochromatic and telomeric regions indicating an increased breakage of these regions. This may indicate that epigenetic alterations and critically short telomeres predispose for the generation of chromosome aberrations in CLL. Telomere shortening and chromosomal instability are believed to play an important role in the development of neoplasia. Recently, it was shown that short telomeres in CLL are associated with a poor survival and increased genetic complexity (G Roos et al, Blood111, 2246–2252 (2008)). So far, published data are only available on the average telomere length in CLL, but not on the telomere length of individual chromosomes. We used a new technique, telomere/centromere-fluorescence in situ hybridization (T/C-FISH), which combines fluorescence R-banding and FISH using a probe against the telomere repeats to measure the telomere length of each chromosome arm. In line with previous results, patients with CLL showed significantly shorter telomeres than those of healthy controls. Comparing the telomere lengths of distinct chromosome arms with specific aberrations, there was no significant association. In addition, we could compare the telomere lengths of cells with aberrations and cells without aberrations within one patient. Aberrant metaphases of the same patient showed significantly shorter telomeres than metaphases with a normal karyotype (p<0.05). Thus, telomere shortening is not a basic mechanism affecting all hematopoietic cells in CLL patients, e.g. due to aging, but affects only the malignant cells, indicating that telomere attrition is involved in the pathogenesis of CLL with complex karyotypes. Disclosures: No relevant conflicts of interest to declare.
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Cuneo, A., JL Michaux, A. Ferrant, et al. "Correlation of cytogenetic patterns and clinicobiological features in adult acute myeloid leukemia expressing lymphoid markers [see comments]." Blood 79, no. 3 (1992): 720–27. http://dx.doi.org/10.1182/blood.v79.3.720.720.
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Abstract Cytogenetic, biomolecular, and clinicopathologic features were retrospectively studied in 34 adult patients with acute myelogenous leukemia expressing one or more of the following lymphoid-associated markers (LMs): CD7, CD2, CD10, CD19, CD22, TdT. Six patients showed 11q23 rearrangements (group I); three patients had the classic Ph chromosome (group II); 15 patients had aberrations of the myeloid type (group III), including four patients with structural aberrations of 13q or trisomy 13, three patients with 7q and 1q anomalies, and two patients with trisomy 11q. Ten patients had a normal karyotype (group IV). Anomalies exclusively associated with lymphoid malignancies were not seen. Ig H and/or T-cell receptor genes were found to be rearranged in 50% and 66% of patients in cytogenetic groups I and II, respectively, versus 8% in group III and 12% in group IV. Likewise, more than one LM was more frequently detected in groups I and II. In group III, two of four patients with aberrations of chromosome 13 expressed two or more lymphoid features. Clinically, patients belonging to cytogenetic groups I and II were generally young, presented with a high white blood cell (WBC) count, and had a low complete remission rate. Survival in Ph chromosome-positive cases was uniformly short. We conclude that although there is no cytogenetic anomaly specifically associated with acute myelogenous leukemia expressing LM, a Morphologic, Immunologic, and Cytogenetic classification may constitute a working basis for further studies aimed at a better definition of clinicopathologic features and optimal treatment strategies for these leukemias.
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Cuneo, A., JL Michaux, A. Ferrant, et al. "Correlation of cytogenetic patterns and clinicobiological features in adult acute myeloid leukemia expressing lymphoid markers [see comments]." Blood 79, no. 3 (1992): 720–27. http://dx.doi.org/10.1182/blood.v79.3.720.bloodjournal793720.
Full textAbstract:
Cytogenetic, biomolecular, and clinicopathologic features were retrospectively studied in 34 adult patients with acute myelogenous leukemia expressing one or more of the following lymphoid-associated markers (LMs): CD7, CD2, CD10, CD19, CD22, TdT. Six patients showed 11q23 rearrangements (group I); three patients had the classic Ph chromosome (group II); 15 patients had aberrations of the myeloid type (group III), including four patients with structural aberrations of 13q or trisomy 13, three patients with 7q and 1q anomalies, and two patients with trisomy 11q. Ten patients had a normal karyotype (group IV). Anomalies exclusively associated with lymphoid malignancies were not seen. Ig H and/or T-cell receptor genes were found to be rearranged in 50% and 66% of patients in cytogenetic groups I and II, respectively, versus 8% in group III and 12% in group IV. Likewise, more than one LM was more frequently detected in groups I and II. In group III, two of four patients with aberrations of chromosome 13 expressed two or more lymphoid features. Clinically, patients belonging to cytogenetic groups I and II were generally young, presented with a high white blood cell (WBC) count, and had a low complete remission rate. Survival in Ph chromosome-positive cases was uniformly short. We conclude that although there is no cytogenetic anomaly specifically associated with acute myelogenous leukemia expressing LM, a Morphologic, Immunologic, and Cytogenetic classification may constitute a working basis for further studies aimed at a better definition of clinicopathologic features and optimal treatment strategies for these leukemias.
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Sawyer, Jeffrey R., Guido Tricot, Sandy Mattox, Sundar Jagannath, and Bart Barlogie. "Jumping Translocations of Chromosome 1q in Multiple Myeloma: Evidence for a Mechanism Involving Decondensation of Pericentromeric Heterochromatin." Blood 91, no. 5 (1998): 1732–41. http://dx.doi.org/10.1182/blood.v91.5.1732.
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Abstract Karyotypes in multiple myeloma (MM) are complex and exhibit numerous structural and numerical aberrations. The largest subset of structural chromosome anomalies in clinical specimens and cell lines involves aberrations of chromosome 1. Unbalanced translocations and duplications involving all or part of the whole long arm of chromosome 1 presumably occur as secondary aberrations and are associated with tumor progression and advanced disease. Unfortunately, cytogenetic evidence is scarce as to how these unstable whole-arm rearrangements may take place. We report nonrandom, unbalanced whole-arm translocations of 1q in the cytogenetic evolution of patients with aggressive MM. Whole-arm or “jumping translocations” of 1q were found in 36 of 158 successive patients with abnormal karyotypes. Recurring whole-arm translocations of 1q involved chromosomes 5,8,12,14,15,16,17,19,21, and 22. A newly delineated breakpoint present in three patients involved a whole-arm translocation of 1q to band 5q15. Three recurrent translocations of 1q10 to the short arms of different acrocentric chromosomes have also been identified, including three patients with der(15)t(1;15)(q10;p10) and two patients each with der(21)t(1;21)(q10;p13) and der(22)t(1;22) (q10;p10). Whole-arm translocations of 1q10 to telomeric regions of nonacrocentric chromosomes included der(12)t(1;12) (q10;q24.3) and der(19)t(1;19)(q10;q13.4) in three and two patients, respectively. Recurrent whole-arm translocations of 1q to centromeric regions included der(16)t(1;16)(q10;q10) and der(19)t(1;19)(q10;p10). The mechanisms involved in the 1q instability in MM may be associated with highly decondensed pericentromeric heterochromatin, which may permit recombination and formation of unstable translocations of chromosome 1q. The clonal evolution of cells with extra copies of 1q suggests that this aberration directly or indirectly provides a proliferative advantage.
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Sawyer, Jeffrey R., Guido Tricot, Sandy Mattox, Sundar Jagannath, and Bart Barlogie. "Jumping Translocations of Chromosome 1q in Multiple Myeloma: Evidence for a Mechanism Involving Decondensation of Pericentromeric Heterochromatin." Blood 91, no. 5 (1998): 1732–41. http://dx.doi.org/10.1182/blood.v91.5.1732.1732_1732_1741.
Full textAbstract:
Karyotypes in multiple myeloma (MM) are complex and exhibit numerous structural and numerical aberrations. The largest subset of structural chromosome anomalies in clinical specimens and cell lines involves aberrations of chromosome 1. Unbalanced translocations and duplications involving all or part of the whole long arm of chromosome 1 presumably occur as secondary aberrations and are associated with tumor progression and advanced disease. Unfortunately, cytogenetic evidence is scarce as to how these unstable whole-arm rearrangements may take place. We report nonrandom, unbalanced whole-arm translocations of 1q in the cytogenetic evolution of patients with aggressive MM. Whole-arm or “jumping translocations” of 1q were found in 36 of 158 successive patients with abnormal karyotypes. Recurring whole-arm translocations of 1q involved chromosomes 5,8,12,14,15,16,17,19,21, and 22. A newly delineated breakpoint present in three patients involved a whole-arm translocation of 1q to band 5q15. Three recurrent translocations of 1q10 to the short arms of different acrocentric chromosomes have also been identified, including three patients with der(15)t(1;15)(q10;p10) and two patients each with der(21)t(1;21)(q10;p13) and der(22)t(1;22) (q10;p10). Whole-arm translocations of 1q10 to telomeric regions of nonacrocentric chromosomes included der(12)t(1;12) (q10;q24.3) and der(19)t(1;19)(q10;q13.4) in three and two patients, respectively. Recurrent whole-arm translocations of 1q to centromeric regions included der(16)t(1;16)(q10;q10) and der(19)t(1;19)(q10;p10). The mechanisms involved in the 1q instability in MM may be associated with highly decondensed pericentromeric heterochromatin, which may permit recombination and formation of unstable translocations of chromosome 1q. The clonal evolution of cells with extra copies of 1q suggests that this aberration directly or indirectly provides a proliferative advantage.
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Sawyer, Jeffery R., Erming Tian, Brian A. Walker, et al. "An Acquired High-Risk Chromosome Instability Phenotype in Multiple Myeloma: Jumping 1q Syndrome." Blood 132, Supplement 1 (2018): 4489. http://dx.doi.org/10.1182/blood-2018-99-115090.
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Abstract Introduction Chromosome instability (CIN) is a driver of copy number aberrations (CNAs) in cancer, and is a major factor leading to tumor heterogeneity and resistance to therapy. By definition, CIN is an increased rate or ongoing acquisition and accumulation of CNAs and not simply the existence of structurally and numerically abnormal aneuploid clones. In multiple myeloma (MM), the most common whole-chromosome CNAs involve either hyperdiploid or non-hyperdiploid clones. Secondary segmental CNAs are associated with high-risk (HR) in MM and involve gains of 1q21 and deletions of 17p (del17p). These types of intra-chromosomal segmental CNAs are also found in the CIN phenotypes of the autosomal recessive (AR) chromosome instability syndromes. These syndromes include Fanconi anemia, Bloom's syndrome, and ICF syndrome (Immunodeficiency, Centromeric instability and Facial anomalies). These chromosome instability syndromes display a spectrum of aberrations characterized by higher rates of chromosomal breaks, chromatid exchanges, quadriradials, and pericentromeric aberrations. In particular, patients with ICF syndrome show a marked increase of 1q12 pericentromeric instability including 1q12 decondensation, triradials, multibranched chromosomes 1q, and 1q micronuclei. ICF patients also show transient 1q aberrations including isochromosome 1q (iso1q) and unbalanced translocations of 1q to 9q and 16q. In MM, we have previously reported increasing pericentromeric instability during tumor progression resulting in increasing CNAs of 1q21 by unbalanced jumping translocations of 1q12 (JT1q12). Strikingly, in a subset of MM patients with 1q21 CNAs of ≥ 5 a distinct cytogenetic phenotype emerges which demonstrates transient 1q12 aberrations including 1q12 decondensation, triradials, and multibranched chromosomes 1q morphologically identical to those seen in ICF patients. In MM this chromosome instability leads to a cascade of increasing clonal 1q21 duplications, iso 1qs, and unbalanced 1q translocations with 16q and 17p, resulting in losses in these receptor chromosomes (RC) and massive intra-clonal CNA heterogeneity. Methods To investigate the cytogenetic impact and progression of high CNAs of 1q21, we performed a comprehensive metaphase analysis of 50 patients showing segmental aneuploidies with 4 or more copies of 1q by G-banding. Locus specific FISH and spectral karyotyping were used to identify the key transient unstable and clonal structural aberrations of 1q12 resulting in segmental aneuploidies in the derivative RCs. Probe for 1q12 (Vysis) was used according to the manufacturer's protocol. Locus specific BAC clones for 1q21 (CKS1B) and 17p (TP53) were prepared and analyzed as previously described (Sawyer et al., Blood 123: 2014). IGH translocations were investigated with IGH break apart probes (Vysis). Results Data for 50 patients including CNAs of 1q21 of ≥ 4, IGH translocations, del(17p), derivative RCs, are presented. The t(4;14) was found in 15 patients, del(17p) in 23, and both aberrations were found in 8 patients. All patients showed unbalanced gains of 1q and deletions of RCs, the most frequent being 7 patients with der(1;16) and 6 with iso1q. In four of the 23 patients with del(17p), the deletion was due to a JT1q12 to 17p. Seven patients with 1q21 CNAs of ≥ 5 showed profound instability involving the 1q12 satellite DNA, demonstrating both transient and clonal aberrations driving the 1q21 CNAs. These aberrations included unstable 1q21 triplications, JT1q12s, iso1q formation with intra-arm 1q12 CNAs, and region specific breakage-fusion-bridge cycle amplifications. Conclusions Among patients with ≥ 5 CNAs of 1q21, a subset develop an acquired HR chromosome instability phenotype with an elevated rate of 1q12 pericentromeric instability characterized by concomitant deletions in 16q, iso1q, del(17p), and intra-arm segmental instability. These patients show pronounced instability in the 1q12 satellite DNA, morphologically identical to ICF syndrome, suggesting hypomethylation of this region as a driver of both 1q21 CNAs and deletions in RCs. We hypothesize that region specific hypomethylation of 1q12 provides the genomic background for the onset of an acquired 1q12 chromosome instability phenotype in MM similar to that found in ICF syndrome. For myeloma patients demonstrating this 1q12 chromosome instability phenotype we propose the term "jumping 1q syndrome." Disclosures Epstein: University of Arkansas for Medical Sciences: Employment. Davies:Amgen: Consultancy, Membership on an entity's Board of Directors or advisory committees; ASH: Honoraria; Abbvie: Consultancy; TRM Oncology: Honoraria; Celgene: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Takeda: Consultancy, Membership on an entity's Board of Directors or advisory committees; MMRF: Honoraria; Janssen: Consultancy, Honoraria. Morgan:Takeda: Consultancy, Honoraria; Celgene: Consultancy, Honoraria, Research Funding; Janssen: Research Funding; Bristol-Myers Squibb: Consultancy, Honoraria.
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Bobylova, M. Yu, M. O. Abramov, A. V. Kovalskaya, A. A. Alikhanov, and K. Yu Mukhin. "A case of inversion of chromosome 4 and an unbalanced transloca- tion between the short arm of chromosome 4 and long arm of chromosome 18 in a girl: evolution of clinical and electroencephalographic manifestations." Russian Journal of Child Neurology 15, no. 3-4 (2021): 78–91. http://dx.doi.org/10.17650/2073-8803-2020-15-3-4-78-91.
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We report a case of a girl with a chromosomal disorder that has never been described in the literature: inversion of chromosome 4 with an unbalanced translocation between the short arm of chromosome 4 and long arm of chromosome 18. Clinical manifestations of this syndrome included severe growth retardation, very slow weight gain, optic nerve hypoplasia, pronounced delay in mental and motor development, and epilepsy with focal hemiclonic fever-related seizures of varying location. The patient has multiple stigmas of dysembryogenesis, but no abnormalities in the development of internal organs. The somatic status is complicated by chronic liquid aspiration and sleep apnea. Magnetic resonance imaging has demonstrated agenesis of the corpus callosum. In this article, we have summarized the results of clinical observation and electroencephalography findings obtained during several years. The type of epilepsy in this girl does not match Wolf–Hirschhorn syndrome (which is determined by her karyotype), but is similar to epilepsy in patients with aberrations of the long arm of chromosome 18.
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Cuneo, A., C. Mecucci, S. Kerim, et al. "Multipotent stem cell involvement in megakaryoblastic leukemia: cytologic and cytogenetic evidence in 15 patients." Blood 74, no. 5 (1989): 1781–90. http://dx.doi.org/10.1182/blood.v74.5.1781.1781.
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Abstract Cytologic and cytogenetic results obtained from patients fulfilling the FAB criteria for the diagnosis of acute nonlymphocytic leukemia (ANLL) of megakaryocytic lineage (ANLL-M7) are reported. Eleven cases were de novo ANLL-M7, of whom three presented with acute myelofibrosis. Four cases were megakaryoblastic transformations of chronic myelogenous leukemia (two cases), refractory anemia with excess of blasts (one case), and polycythemia vera (one case). Four patients showed a minority of granular blasts, with occasional Auer rods in one. Positive myeloperoxidase and/or sudan black-B stainings and CD13 positivity in these cases were consistent with the presence of a myeloid involvement. Morphologic evidence of associated myelodysplastic features was detected in all evaluable patients with de novo ANLL-M7. These cytologic findings indicate that ANLL-M7 may frequently represent a multilineage proliferation. Cytogenetic studies revealed -7/7q- and +8, alone or in combination with additional aberrations, in three cases each. Rearrangements involving bands 3q21 or 3q26 were seen in two patients and +21, as an additional aberration, in one. Other structural rearrangements all observed in a single patient were inv(16)(p13q22) at megakaryoblastic relapse with bone marrow eosinophilia, t(13;20)(q13 or 14;q11), del(20)(q11), and der(7)t(7;17)(p14;q22). Most breakpoints of these aberrations are located at bands frequently rearranged in malignant myeloid stem cell disorders. A review of 31 cases of the literature showed a frequent occurrence of -7/7q- and -5/5q- in ANLL- M7. Many of the chromosome aberrations so far described in ANLL-M7 appear to be shared by a spectrum of myeloid neoplasias and may be related to mechanisms conferring proliferative advantage to undifferentiated stem cells.
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Cuneo, A., C. Mecucci, S. Kerim, et al. "Multipotent stem cell involvement in megakaryoblastic leukemia: cytologic and cytogenetic evidence in 15 patients." Blood 74, no. 5 (1989): 1781–90. http://dx.doi.org/10.1182/blood.v74.5.1781.bloodjournal7451781.
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Cytologic and cytogenetic results obtained from patients fulfilling the FAB criteria for the diagnosis of acute nonlymphocytic leukemia (ANLL) of megakaryocytic lineage (ANLL-M7) are reported. Eleven cases were de novo ANLL-M7, of whom three presented with acute myelofibrosis. Four cases were megakaryoblastic transformations of chronic myelogenous leukemia (two cases), refractory anemia with excess of blasts (one case), and polycythemia vera (one case). Four patients showed a minority of granular blasts, with occasional Auer rods in one. Positive myeloperoxidase and/or sudan black-B stainings and CD13 positivity in these cases were consistent with the presence of a myeloid involvement. Morphologic evidence of associated myelodysplastic features was detected in all evaluable patients with de novo ANLL-M7. These cytologic findings indicate that ANLL-M7 may frequently represent a multilineage proliferation. Cytogenetic studies revealed -7/7q- and +8, alone or in combination with additional aberrations, in three cases each. Rearrangements involving bands 3q21 or 3q26 were seen in two patients and +21, as an additional aberration, in one. Other structural rearrangements all observed in a single patient were inv(16)(p13q22) at megakaryoblastic relapse with bone marrow eosinophilia, t(13;20)(q13 or 14;q11), del(20)(q11), and der(7)t(7;17)(p14;q22). Most breakpoints of these aberrations are located at bands frequently rearranged in malignant myeloid stem cell disorders. A review of 31 cases of the literature showed a frequent occurrence of -7/7q- and -5/5q- in ANLL- M7. Many of the chromosome aberrations so far described in ANLL-M7 appear to be shared by a spectrum of myeloid neoplasias and may be related to mechanisms conferring proliferative advantage to undifferentiated stem cells.
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Ta, Lan, Adrian Zordan, Bruce Mercer, Lynda J. Campbell, and Ruth N. MacKinnon. "The Breakage-Fusion-Bridge Cycle Producing MLL Amplification in a Case of Myelodysplastic Syndrome." Journal of Cancer Research 2013 (July 18, 2013): 1–6. http://dx.doi.org/10.1155/2013/452809.
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Telomere loss may lead to chromosomal instability via the breakage-fusion-bridge (BFB) cycle which can result in genetic amplification and the formation of ring and dicentric chromosomes. This cycle continues until stable chromosomes are formed. The case of a 72-year-old female with refractory anaemia with excess blasts type 2 illustrates these events. Conventional cytogenetics produced a complex karyotype which included unstable abnormalities of chromosomes 11, 12, and 15. Fluorescence in situ hybridization (FISH) analyses including multicolor-FISH (M-FISH) and multicolor-banding (M-BAND) revealed multiple clonal populations with 5 copies of MLL on either a ring chromosome composed entirely of chromosome 11 material or a derivative chromosome composed of chromosomes 11, 12, and 15. The FISH results also clarified the likely evolution of the karyotypic complexity. The simplest cell line contained a dic(12;15) in addition to copy number aberrations that are typical of MDS or AML. As the disease progressed, a ring 11 was formed. Subsequently, the ring 11 appears to have unwound and inserted itself into the dic(12;15) chromosome followed by an inversion of the derivative chromosome, producing a der(11;15;12). Telomeric loss and BFB cycles appear to have played an important role in the chromosomal rearrangements and clonal evolution demonstrated in the karyotype.
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Trimborn, M., T. Liehr, B. Belitz, et al. "Prenatal Diagnosis and Molecular Cytogenetic Characterization of an Unusual Complex Structural Rearrangement in a Pregnancy Following Intracytoplasmic Sperm Injection (ICSI)." Journal of Histochemistry & Cytochemistry 53, no. 3 (2005): 351–54. http://dx.doi.org/10.1369/jhc.4b6412.2005.
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We report on a balanced complex chromosomal aberration detected in a fetus after amniocentesis. The pregnancy was achieved after intracytoplasmic sperm injection. GTG-banding revealed a complex structurally rearranged karyotype with a translocation between chromosomes 5 and 15 and an additional paracentric inversion in the der(15) between bands 5q11.2 and 5q15. Ag-NOR staining showed an interstitial active nuclear organizer region in the der(15). Molecular cytogenetic analyses using whole-chromosome–painting probes, comparative genomic hybridization, and multicolor banding did not point to further structural aberrations or imbalances. Therefore, a complex rearrangement with three breakpoints has occurred, and the karyotype can be described as 46,XX,der(5)t(5;15)(q11.2;p12),der(15)t(5;15)(q11.2;p12)inv(5)(q11.2q15).
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Göhring, Gudrun, Simone Feurstein, Winfried Hofmann, Arnold Ganser, Hans H. Kreipe, and Brigitte Schlegelberger. "Routes of Clonal Evolution Into Complex Karyotypes in Myelodysplastic Syndrome Patients with Del(5q)." Blood 120, no. 21 (2012): 522. http://dx.doi.org/10.1182/blood.v120.21.522.522.
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Abstract Abstract 522 Introduction: A complex karyotype, detected in approximately 10%-15% of patients with myelodysplastic syndromes (MDS), is associated with a very short median survival and a high risk of transformation into AML. The most frequent chromosome aberration in complex karyotypes is a deletion of 5q (del(5q)). It is still unclear, how complex karyotypes develop. One possibility is via stepwise accumulation of chromosome aberrations according to the so-called Vogelstein model (Fearon ER, Vogelstein B, Cell 1990; 61:759–67). Another possibility is a one-step catastrophic event called chromothripsis that seems to be associated with TP53 inactivation (Rausch T et al., Cell 2012;148:59–71). We recently described that leukemic progression in low-grade MDS with isolated del(5q) is associated with clonal evolution (Tehranchi R et al., N Engl J Med 2010;363:1025–37, Göhring G et al., Ann Hematol 2010; 89:365–74) and identified TP53 mutations and excessive telomere shortening as driving forces for clonal evolution and leukemic progression in MDS with del(5q) (Jädersten M et al., J Clin Oncol 2011; 29:1971–9, Göhring G et al., Leukemia 2012; 26:356–8). Yet, the modes of clonal evolution and the mechanisms responsible for the induction of chromosomal instability in MDS with isolated del(5q) remain largely unclear. Patients and Methods: Among 1645 patients with MDS and del(5q) investigated cytogenetically in our institution, 157 patients (9.5%) acquired additional aberrations and thus underwent clonal evolution. We reviewed the cytogenetic follow-up data of the 157 patients and carefully evaluated all additional aberrations, particularly those of complex karyotypes, which are defined as at least 3 aberrations, i.e. del(5q) and two additional chromosome abnormalities. Moreover, we investigated the clonal heterogeneity and the presence of independent clones, defined as clones that do not contain a del(5q). Results: During follow-up, 76 of 157 patients (48%) acquired two or more aberrations, thus evolving into a complex karyotype. Eighty-nine of 157 patients (57%) underwent a stepwise accumulation of additional aberrations (range 1–8, median: 1), while 38 patients (24%) developed highly complex clones (no of aberrations: 3–35, median: 7.5) at one time point during follow-up. This “catastrophic” route led to the development of a complex karyotype significantly more frequently than the stepwise accumulation of chromosome aberrations (38 of 38 cases compared to 38 of 89 patients; p<0.00001). In 12 cases, the complex clones were preceded by a clone containing one additional aberration, e.g. −7, del(12p) or del(17p). Independent clones that did not contain a del(5q) were detected in 43 of 157 patients (27%). A few aberrations were seen significantly more frequently in complex karyotypes than as single additional aberrations, e.g. −7/del(7q) (p=0.0001), del(9p) (p=0.01), +11/add(11q) (p=0.0003), −11/del(11q) (p=0.03), −16/del(16q) (p=0.0006), −17/del(17p) (p=0.00001), and +22/add(22q) (p=0.006). Trisomy 8 (p=0.008) and trisomy 21 (p=0.00001) occurred mostly in del(5q) clones with one additional aberration. Trisomy 8 was the most frequent aberration in independent clones. Conclusions: Although MDS with del(5q) is assumed to be a genetically stable hematologic neoplasm, clonal evolution, even into complex karyotypes, occurs in a significant proportion of patients. There are two routes of clonal evolution. One route of stepwise acquisition of additional aberrations resulted in clonal selection of clones that had accumulated mostly only one or two additional aberrations. In contrast, the other route led to an immediate development of highly complex clones. In some of these cases, this catastrophic event was preceded by the acquisition of one aberration, repeatedly by loss of 12p or loss of 17p harboring the ETV6/TEL and TP53 genes, respectively. These data provide further evidence that the inactivation of TP53 seems to play an important role in clonal evolution and leukemic progression. Disclosures: No relevant conflicts of interest to declare.
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Nordgren, Ann, Filip Farnebo, Bertil Johansson, et al. "Identification of numerical and structural chromosome aberrations in 15 high hyperdiploid childhood acute lymphoblastic leukemias using spectral karyotyping." European Journal of Haematology 66, no. 5 (2001): 297–304. http://dx.doi.org/10.1034/j.1600-0609.2001.066005297.x.
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Viardot, Andreas, Peter Möller, Josef Högel, et al. "Clinicopathologic Correlations of Genomic Gains and Losses in Follicular Lymphoma." Journal of Clinical Oncology 20, no. 23 (2002): 4523–30. http://dx.doi.org/10.1200/jco.2002.12.006.
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PURPOSE: To evaluate the clinical relevance of genomic aberrations in follicular lymphomas (FLs). PATIENTS AND METHODS: In this study, we analyzed 124 biopsy samples of patients with FL using comparative genomic hybridization. RESULTS: In 87 cases (70%), genomic imbalances were detectable. The most frequent aberrations were gains of chromosome arms 7p (21 patients), 7q (21 patients), Xp (16 patients), 12q (15 patients), and 18q (14 patients) as well as losses on 6q (21 patients). Grades 2 and 3 according to the World Health Organization classification correlated with a more complex karyotype (P < .0001). In a subset of 82 patients, a comprehensive clinical data set was available. In a multivariate analysis including all clinical risk factors of the International Prognostic Index as well as genomic aberrations, the loss of material on chromosomal bands 6q25q27 was the strongest predictor of a shorter survival (P = .0001; hazard ratio, 6.5), followed by elevated serum lactate dehydrogenase level (P = .0009; hazard ratio, 4.9), the presence of more than one extranodal manifestation (P = .017; hazard ratio, 4.2), and age greater than 60 years (P = .022; hazard ratio, 2.6). CONCLUSION: These data indicate that genomic aberrations may contribute significantly to risk assessment in patients with FL, the majority of whom are included in low-risk groups using established clinical prognostic scores.
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Reedijk, Ardine, Gertjan Kaspers, Marta Fiocco, et al. "Clinical Impact of Additional Cytogenetic Aberrations and Treatment in Pediatric t(8;21)-Positive AML: Results from an International Retrospective I-BFM-SG Study." Blood 120, no. 21 (2012): 884. http://dx.doi.org/10.1182/blood.v120.21.884.884.
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Abstract Abstract 884 Core binding factor AML is generally considered to have a favorable prognosis, but in several studies, patients with a t(8;21)(q22;q22) RUNX1/RUNX1T1 have relapse rates greater than 30%. Factors that reliably discriminate between pediatric AML patients with t(8;21) who remain in remission and those who relapse have not yet been described. In this study, we aim to identify markers that are present at diagnosis, predict clinical outcome, and may be useful for risk stratification and/or risk-adapted therapy. From 19 childhood cancer study groups worldwide, we collected data from 916 patients with de novo AML positive for t(8;21) and/or AML1-ETO fusion gene enrolled from 1987 to 2010. All complete karyotypes (n=838) were centrally reviewed and classified according to type and number of aberrations. Recurrent aberrations (occurring in at least 10 patients) were considered for statistical analysis. These aberrations included deletion of one sex chromosome, del(9q), abnormality of 7q, trisomy 4 and trisomy 8. Patients were also subdivided according to the number of abnormalities in association with t(8;21). Achievement of complete remission (CR), 5 year (y) overall survival (OS), 5y event-free survival (EFS) and cumulative incidence of relapse (CIR) were analysed for all potential prognostic factors, and regarding treatment for anthracyclines and allogenic stem cell transplantation. All variables significant at the 0.1 level in univariate analysis were entered into a multivariable Cox proportional hazards regression model. Variables were removed if they were not significant at the level of 0.05 on the basis of the likelihood ratio test. The 838 patients with complete karyotypes had a CR-rate, 5y OS, EFS and CIR of 92.5%, 74.2% (95%CI 71.5–76.6), 59.8% (95%CI 56.5–62.9) and 28.1% (95%CI 24.9–31.3), respectively. In total 229 patients died; including 37 who did not achieve CR, 125 after relapse and 67 in remission during or after treatment. Clinical features and treatment related factors significantly associated with inferior OS were age > 15 y, male gender, WBC ≥20×109/L, low dose anthracyclines in induction (≤150mg/m2 in the first course of chemotherapy) and gain of chromosome 4. In multivariate analysis, age (15+ vs. 0–4 years HR = 2.27 (95% CI 1.42–3.63), p=0.001), high WBC (HR = 1.56 (95%CI 1.20–2.04), p=0.001), and gain of chromosome 4 (HR = 2.70 (95%CI 1.52–4.79) p = 0.001) remained significant. Factors associated with inferior EFS were male gender, WBC ≥20×109/L, CNS involvement, percentage of blasts <60 % in bone marrow at diagnosis, low dose anthracyclines in induction (≤150mg/m2) and gain of chromosome 4. In multivariate analysis, high WBC (HR = 1.51 (95%CI 1.19–1.91), p= 0.001), low dose anthracyclines in induction (HR = 1.33 (95%CI 1.04–1.71), p = 0.021) and gain of chromosome 4 (HR = 2.84 (95%CI 1.67–4.80), p < 0.001) were significant. Factors associated with higher CIR were high WBC (HR = 1.50 (95%CI 1.13–2.00), p= 0.006), low dose anthracyclines in induction (HR = 1.42 (95%CI 1.03–1.97), p = 0.034), gain of chromosome 4 (HR = 2.31 (95%CI 1.21–4.39), p= 0.011) and no allogeneic stem cell transplantation in first CR (HR = 2.58 (95%CI 1.51–4.39, p < 0.001). In conclusion, this is the largest pediatric cohort of t(8;21)-positive AML described to date, with several new findings. Apart from the well known prognostic factors: age and WBC at initial diagnosis, we found that patients who received more than 150 mg/m2 of anthracyclines in induction had a lower CIR, and a better EFS and OS. Regarding karyotype, the presence of additional aberrations per se did not impact on outcome. However, in relation to particular additional aberrations, gain of chromosome 4 was associated with a three-fold higher risk of relapse. Disclosures: No relevant conflicts of interest to declare.
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von Neuhoff, Christine, Jutta Bradtke, Martin Zimmermann, et al. "Distribution and Outcome According to Cytogenetics in 502 Paediatric AML Patients Treated in Study AML-BFM 98." Blood 112, no. 11 (2008): 1510. http://dx.doi.org/10.1182/blood.v112.11.1510.1510.
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Abstract Cytogenetic analyses are essential for stratification and prognosis of childhood AML. We analysed the frequency of chromosomal aberrations and the outcome according to the cytogenetic findings in 457 patients with data (91%) out of the total group of 502 patients in study AML-BFM 98. The aim was to evaluate the prognostic impact of specific chromosomal aberrations in a large group of uniformly treated patients. The 502 patients <18 years were diagnosed between 1998 and 2003. According to the AML-BFM risk criteria, patients were assigned to a high risk (HR) and a standard risk (SR) group based on morphology, genetics and response on day 15 of therapy. Cytogenetic and FISH analyses - as well as RT-PCR if indicated - were performed according to standard protocols on bone marrow or peripheral blood prior to therapy. Initial characteristics of patients with or without cytogenetic data were essentially similar; only the percentage of patients with undifferentiated leukaemia was higher in patients without cytogenetic data (20% vs. 2.8%). The number of patients in different karyotypic groups and their outcome are given in the table below: Cytogenetic aberration Patients n (%) 5-year-EFS (SE) % p logrank* 5-year-OS (SE) % p logrank* *in comparison to the total group SE = standard error, OS = overall survival, EFS = event free survival Total patients with cytogenetic data 457 (100) 48 (2) 0.70 62 (2) 0.74 Normal karyotype 105 (23) 42 (5) 0.09 54 (5) 0.11 t(8;21) or AML1-ETO 57 (12) 84 (5) <0.0001 91 (4) <0.0001 t(15;17) or PML-RARα 27 (6) 73 (9) 0.03 92 (6) 0.015 Inversion 16, t(16;16) or CBFβ/MYH11 43 (9) 64 (8) 0.03 85 (6) 0.006 MLL-rearrangements 94 (21) 36 (5) 0.004 50 (5) 0.003 Deletion of 7q 13 (3) 46 (14) 0.84 62 (13) 0.68 Monosomy 7 10 (2) 10 (9) 0.0003 20 (13) 0.0002 Trisomy 8 38 (8) 46 (8) 0.87 64 (8) 0.65 Aberrations involving 12p 9 (2) 11 (10) 0.02 22 (14) <0.01 Aberrations of chromosome 5 12 (3) 67 (14) 0.19 64 (15) 0.58 3 or more chromosomal aberrations 33 (7) 33 (9) 0.06 48 (9) 0.20 Other cytogenetic aberrations 72 (16) 38 (6) 0.10 58 (6) 0.48 Patients without cytogenetic data 45 47(7) 0.70 60 (7) 0.74 Special results: Patients with t(8;21) had a low relapse rate (5-year cumulative incidence [CI] of relapse 17%, SE 6%) and a high overall survival (OS) rate (91%, SE 4%). It was noteworthy that all 15 children with t(8;21) and additional aberrations that were not either del(9q) or −X/−Y were surviving event free (EFS = 100%). We compared the outcome of patients having a translocation t(9;11) [n = 35], t(19;11) [n = 7] or t(10;11) [n = 12] with or without additional cytogenetic aberrations with the total group of patients with MLL-rearrangement: In patients with t(10;11), CI of relapse was 71%, (SE 16%) and significantly higher than in patients with other MLL-rearrangements (43%, SE 6%, pGray = 0.019). Conclusion: Our results in cytogenetic findings confirm the favourable prognosis of the rearrangements t(8;21), t(15;17) and inv(16) and the unfavourable prognosis of complex karyotypes (3 or more chromosomal aberrations) and monosomy 7. It is remarkable that the EFS of patients with a MLL-rearrangement was worse than the average EFS of patients in the high-risk group (n = 317, EFS 39%, SE 3%). Poor outcome in paediatric patients with aberrations of 12p has been described in the context of t(7;12), but not as an independent prognostic factor. The favourable prognosis in patients with aberrations involving chromosome 5 was surprising and would warrant further investigations. Our results confirmed the high relevance of cytogenetics in childhood AML and emphasise that risk groups based on cytogenetic findings should be even more specific.
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Chng, Wee J., Jonathan J. Keats, Esteben Braggio, et al. "Multiple Myeloma (MM) Is Characterized by Genomic Instability Regardless of Ploidy Categories and Degree of Karyotypic Complexity Is an Important Prognostic Factor." Blood 110, no. 11 (2007): 1476. http://dx.doi.org/10.1182/blood.v110.11.1476.1476.
Full textAbstract:
Abstract MM is characterized by widespread genomic instability. Two broad genetic subtypes of MM defined by ploidy exist. Hyperdiploid MM (H-MM) is characterized by trisomies of chromosome 3, 5, 7, 9, 11, 15, and 19, and generally lacked primary translocations involving the immunoglobulin heavy chain locus (IgH) whereas the non-hyperdiploid MM (NH-MM) is characterized by primary IgH translocations such as t(11;14), t(4;14) and t(14;16). Using high-density array comparative genomic hybridization (aCGH, Agilent 44K array), we catalogued the different aberrations on each chromosome arm and also the total number of aberrations per tumor (NAPT), as an indication of the degree of genomic instability, in a large cohort of 194 MM patients. Both H-MM and NH-MM have high number of genomic aberrations, 15.8±7.5 (mean ± standard deviation) versus 20.6±17.0 respective. NH-MM has significantly more genomic losses (11.8±11.0 versus 4.1±3.8), whereas H-MM has slightly more genomic gains (11.7±5.0 versus 8.8±9.0). Most of the abnormalities in NH-MM are structural abnormalities whereas they are mainly whole chromosome abnormalities in H-MM. Based on these abnormalities, we cluster the patients using hierarchical clustering. The 2 main branch of the resulting dendogram delineate hyperdiploid and non-hyperdiploid patients. Sub-clusters of each ploidy subtype are apparent. For H-MM, a cluster with mainly trisomies, including that of chromosome 21, and another cluster with additional deletions (13, 16q, and less trisomy 21 and trisomy 11) were apparent. For NH-MM, a group with 1q amplification and 13 deletion, which also tend to have loss of chromosome 4, 6q, 16q and 14, and another group with little abnormalities or just 6q loss, and chromosome 13 and 14 loss were identified. We identified some genetic difference between NH-MM and H-MM in additional to known difference such as the trisomies and chromosome 13 deletion. Loss of chromosome 4 (18% versus 0.9%, p<0.0001), loss of chromosome 14 (33% versus 16%, p=0.02) and loss of chromosome 22 (21% versus 4%, p=0.0008) are more common in NH-MM. Based on the distribution of NAPT, a cut-off of 20 abnormalities per tumor segregate the patients into 2 groups with significantly different survival. Those with greater NAPT have significantly shorter survival (median overall survival of 20 months versus 88 months, Log-rank p=0.006). There is no correlation between NAPT and ploidy or presence of chromosome 1 abnormalities suggesting that genomic complexity itself is associated with survival. Our study showed that both H-MM and NH-MM are genomically unstable although the pattern of abnormalities is distinct. In addition, based on clustering analysis, new pattern of genetic abnormalities are observed that allow further refinement of the ploidy subtypes. In addition, genomic complexity is also an important prognostic factor.
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Zemanova, Zuzana, Kyra Michalova, Libuse Babicka, et al. "Clinical Relevance of Complex Chromosomal Aberrations in Bone Marrow Cells of 107 Children with ETV6/RUNX1 Positive Acute Lymphoblastic Leukemia (ALL)." Blood 108, no. 11 (2006): 2278. http://dx.doi.org/10.1182/blood.v108.11.2278.2278.
Full textAbstract:
Abstract Cryptic translocation t(12;21)(p13;q22) which give origin to the ETV6/RUNX1 hybrid gene can be found by I-FISH in approximately 20–25% of children with B precursor ALL as the most frequent specific aberration. This translocation is generally associated with good outcome. Despite of its favorable prognostic value, late relapses may occur within this group of patients. One of the reasons could be the high instability of the genome of leukemic cells, which is manifested at the chromosomal level by additional aberrations and/or complex chromosomal rearrangements. The aim of the study was to evaluate the significance of the additional chromosomal aberrations for prognosis of children with ETV6/RUNX1 positive ALL. For the assessment of ETV6/RUNX1 fusion gene RT-PCR and/or double target interphase FISH with locus-specific probe (Abbott-Vysis, Des Plaines, Illinois, USA) were used (200 interphase nuclei analyzed, cut-off level 2.5% tested on controls, standard deviation ≤0.5%). Karyotypes were analyzed by conventional and molecular cytogenetic methods. Structural and/or complex chromosomal aberration were verified by FISH with whole chromosome painting probes (Cambio, Cambridge, UK) and/or by mFISH with the "24XCyte" probe kit (MetaSystems GmbH, Altlussheim, Germany). We performed prospective and retrospective study of 107 children with ALL and ETV6/RUNX1 fusion gene detected by RT-PCR and/or I-FISH. Patients were diagnosed between 1995 and 2006, age ranged between 15 months and 16.9 years (median 4.2 years). Relapse appeared in 19 children (17.8%), four of them died. In 64 children (59.8%) we found besides t(12;21)(p13;q22) additional chromosomal aberrations, the most frequently trisomy or tetrasomy of chromosome 21 (20 cases), deletion of non-translocated ETV6 allele (24 cases), deletion of 6q (7 cases) and/or rearrangements of the long arm of chromosome X (6 cases). Complex karyotypes were identified in 38 children (35.5%). In twelve of them variant translocations of chromosomes 12 and 21 with other partners were observed. Event-free survival (EFS) was significantly shorter in patients with additional structural and/or complex aberrations in ETV6/RUNX1 positive cells (p=0.01). In our cohort complex karyotypes indicated poor prognosis. Finding of complex chromosomal aberrations in leukemic cells is accompanied by higher risk of relapse even in those cases where the prognostically positive aberration is primarily present.
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Hyttel, P., D. Viuff, J. Laurincik, et al. "Risks of in-vitro production of cattle and swine embryos: aberrations in chromosome numbers, ribosomal RNA gene activation and perinatal physiology." Human Reproduction 15, suppl 5 (2000): 87–97. http://dx.doi.org/10.1093/humrep/15.suppl_5.87.
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Stopsack, Konrad H., Charles A. Whittaker, Travis A. Gerke, et al. "Aneuploidy drives lethal progression in prostate cancer." Proceedings of the National Academy of Sciences 116, no. 23 (2019): 11390–95. http://dx.doi.org/10.1073/pnas.1902645116.
Full textAbstract:
Aneuploidy, defined as chromosome gains and losses, is a hallmark of cancer. However, compared with other tumor types, extensive aneuploidy is relatively rare in prostate cancer. Thus, whether numerical chromosome aberrations dictate disease progression in prostate cancer patients is not known. Here, we report the development of a method based on whole-transcriptome profiling that allowed us to identify chromosome-arm gains and losses in 333 primary prostate tumors. In two independent cohorts (n = 404) followed prospectively for metastases and prostate cancer-specific death for a median of 15 years, increasing extent of tumor aneuploidy as predicted from the tumor transcriptome was strongly associated with higher risk of lethal disease. The 23% of patients whose tumors had five or more predicted chromosome-arm alterations had 5.3 times higher odds of lethal cancer (95% confidence interval, 2.2 to 13.1) than those with the same Gleason score and no predicted aneuploidy. Aneuploidy was associated with lethality even among men with high-risk Gleason score 8-to-10 tumors. These results point to a key role of aneuploidy in driving aggressive disease in primary prostate cancer.
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Hernandes, Marina Araújo Fonzar, Terezinha de Jesus Marques-Salles, Hasmik Mkrtchyan, et al. "Extra Copies of der(21)t(12;21) plus Deletion ofETV6Gene due to dic(12;18) in B-Cell Precursor ALL with Poor Outcome." Case Reports in Genetics 2012 (2012): 1–4. http://dx.doi.org/10.1155/2012/186532.
Full textAbstract:
Acute lymphoblastic leukemia (ALL), CD10+ B-cell precursor, represents the most frequent type of childhood ALL from 3 to 6 years of age. The t(12;21)(p13;q22) occurs in 25% of cases of B-cell precursor ALL, it is rare in children less than 24 months and have been related to good prognosis. Some relapse cases and unfavorable prognosis in ALL CD10+ are associated with t(12;21) bearing additional aberrations as extra copies of chromosome 21 andETV6gene loss. This report describes the case of a 15 month-year old girl, who displayed a karyotype with addition on chromosome 12p plus trisomy 10 and tetrasomy of chromosome 21. Molecular cytogenetic studies revealed two extra copies of the der(21) t(12;21), trisomy 10 and deletion of the secondETV6gene due to the dic(12;18). These findings show the great importance of molecular cytogenetic studies to clarify complex karyotypes, to define prognostic, to carry out risk group stratification and to support correctly disease treatment in childhood acute lymphoblastic leukemia.
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Bharathi, T., S. Gnanamurthy, D. Dhanavel, and M. Ariraman. "Induced Physical Mutagenesis and its Effect in Cytological Behavior of Ashwagandha (Withania somnifera (L.) Dunal)." International Letters of Natural Sciences 17 (June 2014): 152–61. http://dx.doi.org/10.18052/www.scipress.com/ilns.17.152.
Full textAbstract:
The mitotic effect of physical mutagen gamma rays was observed in the root tip cells of Ashwagandha. The Chromosome analysis has been showed as an important tool for establish variability of the plant seed by use of physical mutagen gamma rays. The gamma rays have of low wavelength and high penetrable power. The plant has tremendous medicinal values and it is known from ancient times. The dry and well matured seeds of ashwagandha were irradiated with different doses of gamma rays viz., 5, 10, 15, 20, 25, 30, 35, 40, 45 and 50 KR respectively. The chromosome number of control plant is 2n = 48. The gamma rays affect the normal cytological behavior of ashwagandha species. The chromosomal aberrations increase with increase in the doses of gamma rays to optimum level of 30KR, because it causes changes in the chromosome structure, cellular structure and metabolism of plants. The chromosome aberration like, Sticky metaphase, Precocious moment chromosome, Fragments, Anaphasic bridge, Anaphasic laggard, Telophasic laggard. The present investigation was carried out to study the cytogenetic analysis of the species Withania somnifera. The chromosomal aberration increases with increase in the doses to optimum level (50 KR) of physical mutagen gamma rays.