To see the other types of publications on this topic, follow the link: Chromosome 21 – Aberrations chromosomiques.
Journal articles on the topic 'Chromosome 21 – Aberrations chromosomiques'
Create a spot-on reference in APA, MLA, Chicago, Harvard, and other styles
Consult the top 50 journal articles for your research on the topic 'Chromosome 21 – Aberrations chromosomiques.'
Next to every source in the list of references, there is an 'Add to bibliography' button. Press on it, and we will generate automatically the bibliographic reference to the chosen work in the citation style you need: APA, MLA, Harvard, Chicago, Vancouver, etc.
You can also download the full text of the academic publication as pdf and read online its abstract whenever available in the metadata.
Browse journal articles on a wide variety of disciplines and organise your bibliography correctly.
1
Dubé, Martin, Pierre Morisset, and Janouk Murdock. "Races chromosomiques chez Festuca rubra sensu lato (Poaceae) dans l'est du Québec." Canadian Journal of Botany 63, no. 2 (February 1, 1985): 227–31. http://dx.doi.org/10.1139/b85-026.
Full textAbstract:
Twenty-eight chromosome number determinations in Festuca rubra L. s.l. from eastern Québec show the occurrence of both hexaploids (n = 21) and octoploids (n = 28). Some characters distinguish both cytotypes, but they can be modified by cultivation. All the octoploids are identified as F. diffusa Dumort., an introduced species.
2
Gervais, C., R. Trahan, D. Moreno, and A. M. Drolet. "Le Phragmites australis au Québec: distribution géographique, nombres chromosomiques et reproduction." Canadian Journal of Botany 71, no. 10 (October 1, 1993): 1386–93. http://dx.doi.org/10.1139/b93-166.
Full textAbstract:
A study of Phragmites australis (Cav.) Trin. ex Steud., the common reed, was conducted in Quebec between 1985 and 1991. Its present and former geographical distributions (before and after 1950) were established, the chromosome numbers of 52 individuals were determined, and various observations on the reproduction of this species by seed were made. The geographical distribution was outlined after consultation of 21 north-eastern american herbaria and upon in situ observations along roadsides in most parts of inhabited Québec. Concurrently, 77 representative populations were selected and visited in the summer and fall of 1985, allowing the observation of the degree of flower development, the frequency of seed setting, and the presence of smut, Claviceps microcephala (Wallr.) Tul. The chromosome numbers show a high degree of aneuploidy and vary between 2n = 42 and 59. The nordic populations tend to have a lower chromosome number and a faster flower development. In fact, for a given geographical area and date of collection, the flowers of the individuals with higher chromosome numbers are usually less developed. There is however a persistent problem with the evaluation of the chromosome number of a stand because of internal variations. Seed production is generally very low, but some stations, even nordic, are quite productive (up to 59.2% of flowers with seeds). The seeds are able to germinate under laboratory conditions, but it is not known yet if the plant can reproduce in this manner in the field. The seedlings develop slowly and seem to have poor competitiveness. Key words: Phragmites australis, distribution, chromosome numbers, reproduction, Quebec, weed.
3
Van Opstal, Diane, Jan O. Van Hemel, Bert H. J. Eussen, Annet Van Der Heide, Cardi Van Den Berg, Peter A. In't Veld, and Frans J. Los. "A chromosome 21-specific cosmid cocktail for the detection of chromosome 21 aberrations in interphase nuclei." Prenatal Diagnosis 15, no. 8 (August 1995): 705–11. http://dx.doi.org/10.1002/pd.1970150805.
Full text
4
Lichter, P., T. Cremer, C. J. Tang, P. C. Watkins, L. Manuelidis, and D. C. Ward. "Rapid detection of human chromosome 21 aberrations by in situ hybridization." Proceedings of the National Academy of Sciences 85, no. 24 (December 1, 1988): 9664–68. http://dx.doi.org/10.1073/pnas.85.24.9664.
Full text
5
Mokhtar, M. M. "Chromosomal aberrations in children with suspected genetic disorders." Eastern Mediterranean Health Journal 3, no. 1 (January 15, 1997): 114–22. http://dx.doi.org/10.26719/1997.3.1.114.
Full textAbstract:
Karyotyping was done in 137 children suspected of having chromosomal abnormalities such as genetically uncertain syndromes, multiple congenital anomalies, short stature, dysmorphic features, unclassified mental retardation and Down syndrome. A total of 53 [38.7%] had an abnormal karyotype:trisomy 21 [36;26.3%], trisomy 18 [3;2.2%], trisomy 13 [1;0.7%], partial autosomal aneuploidy [5;3.6%], pericentric inversion of chromosome 9 [2;1.5%], marker chromosome [2;1.5%] and sex chromosome aberrations [4;2.9%]. All of them showed phenotypic-cytogenetic heterogeneity. These findings suggest that cytogenetic analysis is useful in the investigation of children with genetic disorders of unknown origin to confirm clinical diagnosis and to allow for proper genetic counseling
6
Braulke, Friederike, Julie Schanz, Michael Metz, Sven Detken, Joerg Seraphin, Katharina Götze, Catharina Mueller-Thomas, et al. "Detection of Karyotype Evolution From Peripheral Blood by Sequential FISH Analyses of Circulating CD34+ Cells In MDS Patients: Results of the Ongoing German Multicenter Prospective Diagnostic Study." Blood 116, no. 21 (November 19, 2010): 2937. http://dx.doi.org/10.1182/blood.v116.21.2937.2937.
Full textAbstract:
Abstract Abstract 2937 Introduction: Chromosomal aberrations in myelodysplastic syndromes (MDS) play a major role in diagnostics, pathogenesis, prognosis, and, more recently, in treatment allocations. The acquisition of clonal abnormalities in pts with initially normal karyotype, the expansion of an aberrant cell clone with a given anomaly or the occurrence of new abnormalities are called karyotype evolution (KE). A model of stepwise cytogenetic changes is proposed, but only a few systematic studies had focused on this phenomenon as yet. Chromosomal anomalies can be detected by conventional chromosome banding analyses of bone marrow (bm) metaphases and most of them are provable by Fluorescence in Situ Hybridization (FISH) of circulating CD34+ cells from peripheral blood (pb). Aims: To closely follow chromosomal aberrations from pb, to assess karyotype evolution and rare anomalies and to correlate the molecular-cytogenetic results with pb blood counts, bm morphology and treatment modalities. For this purpose, we initiated a German multicenter prospective, non-interventional diagnostic study in October 2008. Methods: Sequential FISH analyses were performed on immunomagnetically enriched circulating CD34+ cells from pb as follows: a “super-panel” (D7/CEP7, EGR1, CEP8, CEP XY, D20, p53, IGH/BCL2, TEL/AML1, RB1, MLL, 1p36/1q25, CSF1R) was used for initial screening, every 12 months during follow-up and in every case of suspected progression. A “standard-panel” (EGR1, D7/CEP7, CEP8, p53, D20, CEP X/Y, TEL/AML1) was performed for analyses at short intervals every 2 months in the 1st year and every 3 months during the 2nd year. Results were also correlated with those of conventional banding and FISH analyses performed on bm samples, which typically were collected every 6 months. Results: As yet, 205 pts have been included in the study. Concerning median age, gender distribution, and MDS subtypes (according to WHO and IPSS) the study cohort was representative for the disease. Up to date, chromosomal aberrations were detectable in 126 pts. (62%) by FISH from pb. Most of them had 1 or 2 anomalies, but there were even pts with 4 or more aberrations. The most common aberrations- as known from other studies based on bm analyses- were del(5q) (64%), aberrations of chromosome 7 (del(7q)/-7) (25%), allelic loss of p53 (12%), +8 (11%), del(20q) (10%) and aberrations of chromosome 21 (del(21q)/-21/+21) (7%). Interestingly, a 12p-deletion was detectable as often as a trisomy 8 (11%), and in most cases as part of complex aberrations. A loss of p53 was significantly associated with aberrations of chromosome 7: 67% of pts with aberrations of chromosome 7 showed an allelic loss of p53 at the same time. In 4 cases, a coexistence of del(7q) and -7 in the same clone was observed. Within a median observation time of 7 months (2-21), a KE was detectable from pb by FISH in 17 pts (13%) out of 135 with at least 2 sequential analyses. In most cases del(7q)/-7 developed as a new anomaly, and was followed in frequency by aberrations of chromosome 21. Conclusions: FISH analyses of enriched circulating CD34+ cells are a feasible, less-invasive method to detect chromosomal aberrations in MDS pts and to follow the clone size from peripheral blood. By that method we are able to observe karyotype evolution as a step wise process in detail and to follow even rare abnormalities to learn more about their clinical and prognostic impact. Disclosures: No relevant conflicts of interest to declare.
7
Haferlach, Claudia, Susanne Schnittger, Tamara Weiss, Wolfgang Kern, Brunangelo Falini, and Torsten Haferlach. "About 17% of AML with NPM1 mutations Show a Specific Pattern of Chromosome Aberrations but These Cases Do Not Differ Prognostically from AML with NPM1 Mutations Carrying a Normal Karyotype." Blood 112, no. 11 (November 16, 2008): 2527. http://dx.doi.org/10.1182/blood.v112.11.2527.2527.
Full textAbstract:
Abstract AML with mutated nucleophosmin gene (AML NPM1mut) usually carries a normal karyotype and will be suggested as a provisional entity in the new WHO classification. Thus far, the impact of chromosome aberrations in AML NPM1mut has not been evaluated in detail. Aim of this study was to determine the incidence and prognostic impact of clonal chromosome aberrations in NPM1mut. We further compared this pattern to additional aberrations in AML with recurrent genetic aberrations: t(8;21)(q22;q22), inv(16)(p13q22)/t(16;16)(p13;q22), t(15;17)(q22;q12) and 11q23-abnormalities leading to an MLL-rearrangement. In total 415 AML (de novo AML: 392, s-AML: 11, t-AML: 12) showing an NPM1 mutation were analyzed by chromosome banding analysis. 71 of these showed clonal chromosome aberrations (17.1%; de novo AML: 63 (16.1%), s-AML: 5 (45.5%), t-AML: 3 (25%); de novo AML vs. s-AML: p=0.024). Overall, 111 chromosome aberrations were observed. The most frequent abnormalities were +8 (n=30), −Y (n=10), +4 (n=9), del(9q) (n=5), +21 (n=4), −7 (n=3), +5 (n=2), +10 (n=2), +13 (n=2),+18 (n=2), del(12p) (n=2), del(20q) (n=2), other non-recurrent balanced aberrations (n=6), other non-recurrent unbalanced aberrations (n=32). For comparison 63 AML with t(8;21), 37 cases with inv(16)/t(16;16), 83 patients with t(15;17) and 83 AML showing a 11q23/MLL-rearrangement were evaluated. 44 (69.7%), 13 (35.1%), 39 (47%), and 28 (43.1%) cases showed clonal chromosome aberrations in addition, respectively. Therefore, additional chromosomal aberrations are more frequent in all these subgroups than in the AML NPM1mut. Similar to NPM1mut cases +8 (n=2), −X/Y (n=32), +4 (n=2), and del(9q) (n=10) were observed. The only other recurrent additional aberrations was del(11q) (n=2). In inv(16)/t(16;16) we also found +8 (n=5) and −Y (n=1). The only other recurring additional aberrations were +22 (n=6) and del(7q) (n=2). In AML with t(15;17) recurring additional abnormalities were +8 (n=12), −Y (n=3), del(9q) (n=2), ider(17)(q10) t(15;17) (n=7). AML with 11q23/MLL-rearrangement showed +4 (n=2), +8 (n=8), +13 (n=2), +19 (n=4), +21(n=4), +22 (n=2), −Y (n=1). Thus, chromosome aberration in AML NPM1mut share many overlaps to those in AML with recurrent aberrations. Furthermore, the prognostic impact of chromosome aberrations in AML NPM1mut was evaluated. No difference with respect to overall survival (OS) and event-free survival (EFS) was observed between AML NPM1mut with a normal (n=344) and an aberrant karyotype (n=71) (OS at 2 yrs 78% vs. 81%, p=0.969; EFS at 2 yrs 40% vs. 50%, median EFS 544 days vs. 522 days, p=0.253). The FLT3-ITD status was available in 400 cases. 127 (38%) of 334 cases with a normal karyotype showed a FLT3-ITD, while in only 16 (24%) of 66 cases with an aberrant karyotype a FLT3-ITD was observed (p=0.035). While the negative prognostic impact of additional FLT3-ITD was confirmed in our cohort, the presence of chromosome aberrations did not influence prognosis neither in the FLT3-ITD negative nor in the FLT3-ITD positive subgroup. In addition, 31 patients with AML NPM1mut were analyzed by chromosome banding analysis at diagnosis and at relapse (median time diagnosis to relapse: 301 days (range: 71–986). 22 cases (71%) showed a normal karyotype both at diagnosis and relapse. In 4 cases a normal karyotype was observed at diagnosis and an aberrant karyotype at relapse (del(9q) (n=2), t(2;11) (n=1), inv(12) (n=1)). One case with +8 at diagnosis showed +8 also at relapse. One case with +4 at diagnosis showed +4 and additional aberrations at relapse. In 1 case clonal regression was observed (+21 -> normal). One case with an unbalanced 1;3-translocation at diagnosis showed a der(17;18) (q10;q10) at relapse and one case with −Y at diagnosis showed a del(3p) at relapse. In conclusion: 1. Frequency of additional chromosome aberrations is low in AML NPM1mut as compared to other genetically defined WHO entities. 2. The pattern of additional chromosome aberrations is overlapping between the 5 groups analyzed. 3. Chromosome aberrations observed at diagnosis in AML NPM1mut do not influence prognosis in comparison to AML NPM1mut with normal karyotype. 4. The karyotype is stable in most AML NPM1mut patients at diagnosis and at relapse. These results point to chromosomal aberrations occurring in AML NPM1mut as secondary events and further support inclusion of AML NPM1mut as a provisional entity in the new WHO classification.
8
Neben, Kai, Christian Giesecke, Silja Schweizer, Anthony D. Ho, and Alwin Krämer. "Centrosome aberrations in acute myeloid leukemia are correlated with cytogenetic risk profile." Blood 101, no. 1 (January 1, 2003): 289–91. http://dx.doi.org/10.1182/blood-2002-04-1188.
Full textAbstract:
Abstract Genetic instability is a common feature in acute myeloid leukemia (AML). Centrosome aberrations have been described as a possible cause of aneuploidy in many human tumors. To investigate whether centrosome aberrations correlate with cytogenetic findings in AML, we examined a set of 51 AML samples by using a centrosome-specific antibody to pericentrin. All 51 AML samples analyzed displayed numerical and structural centrosome aberrations (36.0% ± 16.6%) as compared with peripheral blood mononuclear cells from 21 healthy volunteers (5.2% ± 2.0%; P < .0001). In comparison to AML samples with normal chromosome count, the extent of numerical and structural centrosome aberrations was higher in samples with numerical chromosome changes (50.5% ± 14.2% versus 34.3% ± 12.2%; P < .0001). When the frequency of centrosome aberrations was analyzed within cytogenetically defined risk groups, we found a correlation of the extent of centrosome abnormalities to all 3 risk groups (P = .0015), defined as favorable (22.5% ± 7.3%), intermediate (35.3% ± 13.1%), and adverse (50.3% ± 15.6%). These results indicate that centrosome defects may contribute to the acquisition of chromosome aberrations and thereby to the prognosis in AML.
9
Glasmacher, Axel, Corinna Hahn, Andrea Juttner, Regine Schubert, Barbara Busert, Gesa Schwanitz, and Ingo G. H. Schmidt-Wolf. "Chromosome Aberrations in 130 Patients with Multiple Myeloma Detected by Interphase FISH and Their Diagnostic and Prognostic Relevance." Blood 104, no. 11 (November 16, 2004): 4938. http://dx.doi.org/10.1182/blood.v104.11.4938.4938.
Full textAbstract:
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.
10
Craddock, Nick, and Mike Owen. "Chromosomal Aberrations and Bipolar Affective Disorder." British Journal of Psychiatry 164, no. 4 (April 1994): 507–12. http://dx.doi.org/10.1192/bjp.164.4.507.
Full textAbstract:
Chromosomal abnormalities associated with bipolar disorder may help in the localisation of susceptibility genes for bipolar illness by pinpointing ‘candidate’ regions of the genome for further study using molecular genetic methods. We review descriptions of chromosomal abnormalities in association with bipolar and related affective disorders and evaluate their relevance for localising susceptibility genes for bipolar disorder, using standardised criteria. We found 28 reports. We identified four genomic regions of potential interest: 11q21-25; 15q11-13; chromosome 21; Xq28. It is important that clinicians are able to recognise patients who may have chromosome abnormalities which could help in the localisation of susceptibility genes for psychiatric disorders. We suggest referral for specialist investigation and karyotyping, to a psychiatric genetics research group, of any patient with functional psychosis and one or more of the following: (a) a strong family history of functional psychosis; (b) mental retardation; (c) another disease known to be caused by a single gene; or (d) congenital abnormalities.
11
Kosztolányi, Szabolcs, Bálint Horváth, Diána Hosnyánszki, László Kereskai, Erzsébet Sziládi, Pál Jáksó, Hussain Alizadeh, Károly Szuhai, Donát Alpár, and Béla Kajtár. "Molekuláris citogenetikai vizsgálatok Baranya és Tolna megye plazmasejtes myelomában szenvedő betegein." Orvosi Hetilap 160, no. 24 (June 2019): 944–51. http://dx.doi.org/10.1556/650.2019.31357.
Full textAbstract:
Abstract: Introduction: Plasma cell myeloma is a hematological malignancy with heterogeneous genomic landscape and diverse clinical course. Recurrent chromosomal and subchromosomal aberrations commonly occur in this entity and are associated with the pathogenesis and progression of the disease. The identification of these alterations aids genetic characterization, classification and prognostication of patients. Aim: Molecular cytogenetic investigations of plasma cell myeloma patients treated at the University of Pécs Clinical Center and János Balassa County Hospital of Tolna County, Szekszárd, between 2005 and 2018 were evaluated in our study. Method: 231 patients were screened for genetic aberrations using fluorescence in situ hybridization. Translocations involving the immunoglobulin heavy chain gene, losses of 1p and 17p chromosome arms, gains of 1q chromosome arm and unbalanced aberrations of chromosome 13 were investigated. Losses and gains of 1p, 1q, 5q, 12p, 13q, 16q and 17p chromosome arms were analyzed using multiplex ligation-dependent probe amplification in 42 patients. During the investigated period, 116 bone marrow karyotyping was also performed. Results: In total, 233 genetic aberrations were identified using our targeted approaches; the frequency of specific aberrations correlated with data of the recent literature. Concordance of results gained by fluorescence in situ hybridization and multiplex ligation-dependent probe amplification was 96.2% by analyzing the same chromosome arms. The latter technique revealed 21 additional genetic aberrations in 16/42 patient samples (38%) as compared to fluorescence in situ hybridization. Conclusions: Our results suggest that the combined application of the two molecular cytogenetic methods may facilitate a more detailed characterization of genetic aberrations of plasma cell myeloma patients in Hungary. Orv Hetil. 2019; 160(24): 944–951.
12
Pedersen-Bjergaard, J., P. Philip, SO Larsen, G. Jensen, and K. Byrsting. "Chromosome aberrations and prognostic factors in therapy-related myelodysplasia and acute nonlymphocytic leukemia." Blood 76, no. 6 (September 15, 1990): 1083–91. http://dx.doi.org/10.1182/blood.v76.6.1083.1083.
Full textAbstract:
Abstract Cytogenetic studies of 91 consecutive patients with therapy-related myelodysplasia or overt acute nonlymphocytic leukemia disclosed characteristic defects of chromosome 7 in 48 cases and of chromosome 5 in 21 cases. The chromosome 5 abnormalities were consistently present in all abnormal mitoses at the time of diagnosis, as were the chromosome 7 abnormalities in 45 of the 48 patients. Various abnormalities, primarily of the short arm of chromosome 17, were observed in 13 cases, abnormalities of the long arm of chromosome 21 were observed in 12 cases, and rearrangements of 11q23 were seen in nine cases. Thirteen patients presented a normal karyotype. Previous therapy with alkylating agents, the presence of an initial myelodysplastic phase, and abnormalities of chromosome 7 or 5 were interdependent. Patients with 11q23 rearrangement typically developed overt leukemia of FAB types M4 or M5a without myelodysplasia and with a short latent period. Evaluated by Cox regression analysis, complete remission of the primary malignancy and a malignant lymphoma as primary tumor were the two most important and independent prognostic factors indicating a longer survival (P = .008). In addition, the platelet count at diagnosis was a significant prognostic factor (P = .01). For the subgroup of 62 patients with myelodysplasia, the number of chromosome aberrations, the percentage of blasts in the bone marrow, and the hemoglobin level were other significant and independent prognostic factors (P = .05, .05, and .004, respectively). The most important predictive factor for a favorable response to intensive antileukemic chemotherapy in overt leukemia was the absence of a preceding myelodysplastic phase (P = .0014).
13
Pedersen-Bjergaard, J., P. Philip, SO Larsen, G. Jensen, and K. Byrsting. "Chromosome aberrations and prognostic factors in therapy-related myelodysplasia and acute nonlymphocytic leukemia." Blood 76, no. 6 (September 15, 1990): 1083–91. http://dx.doi.org/10.1182/blood.v76.6.1083.bloodjournal7661083.
Full textAbstract:
Cytogenetic studies of 91 consecutive patients with therapy-related myelodysplasia or overt acute nonlymphocytic leukemia disclosed characteristic defects of chromosome 7 in 48 cases and of chromosome 5 in 21 cases. The chromosome 5 abnormalities were consistently present in all abnormal mitoses at the time of diagnosis, as were the chromosome 7 abnormalities in 45 of the 48 patients. Various abnormalities, primarily of the short arm of chromosome 17, were observed in 13 cases, abnormalities of the long arm of chromosome 21 were observed in 12 cases, and rearrangements of 11q23 were seen in nine cases. Thirteen patients presented a normal karyotype. Previous therapy with alkylating agents, the presence of an initial myelodysplastic phase, and abnormalities of chromosome 7 or 5 were interdependent. Patients with 11q23 rearrangement typically developed overt leukemia of FAB types M4 or M5a without myelodysplasia and with a short latent period. Evaluated by Cox regression analysis, complete remission of the primary malignancy and a malignant lymphoma as primary tumor were the two most important and independent prognostic factors indicating a longer survival (P = .008). In addition, the platelet count at diagnosis was a significant prognostic factor (P = .01). For the subgroup of 62 patients with myelodysplasia, the number of chromosome aberrations, the percentage of blasts in the bone marrow, and the hemoglobin level were other significant and independent prognostic factors (P = .05, .05, and .004, respectively). The most important predictive factor for a favorable response to intensive antileukemic chemotherapy in overt leukemia was the absence of a preceding myelodysplastic phase (P = .0014).
14
Sawyer, Jeffrey, Erming Tian, Christoph Heuck, Qing Zhang, Janet Lukacs, Regina Lichti Binz, Edward Thomas, et al. "Hyperhaploid Multiple Myeloma (MM): A Rare Karyotypic Subgroup Retaining Disomy 18 and 1q12∼23 Amplification." Blood 120, no. 21 (November 16, 2012): 3983. http://dx.doi.org/10.1182/blood.v120.21.3983.3983.
Full textAbstract:
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.
15
Shimoyama, M., T. Abe, K. Miyamoto, K. Minato, K. Tobinai, H. Nagoshi, M. Matsunaga, T. Nomura, T. Tsubota, and T. Ohnoshi. "Chromosome aberrations and clinical features of adult T cell leukemia- lymphoma not associated with human T cell leukemia virus type I." Blood 69, no. 4 (April 1, 1987): 984–89. http://dx.doi.org/10.1182/blood.v69.4.984.984.
Full textAbstract:
Abstract Chromosome aberrations and clinical features of three patients with adult T cell leukemia-lymphoma (ATL) not associated with human T cell leukemia virus type I (HTLV-I) are described. From their clinical features, two patients were diagnosed as acute type and one patient was diagnosed as chronic type, which later converted to acute crisis. Clonal and many chromosomal abnormalities were observed before therapy in the two acute type cases and at relapse in the chronic type case. Karyotype aberrations, including trisomy 3, trisomy 7, trisomy 21, del(6)(q21), del(10)(p13), 14q11 translocation, and loss of X chromosome, all of which are frequently found in HTLV-I associated ATL, were also seen in these cases of HTLV-I-negative ATL.
16
Shimoyama, M., T. Abe, K. Miyamoto, K. Minato, K. Tobinai, H. Nagoshi, M. Matsunaga, T. Nomura, T. Tsubota, and T. Ohnoshi. "Chromosome aberrations and clinical features of adult T cell leukemia- lymphoma not associated with human T cell leukemia virus type I." Blood 69, no. 4 (April 1, 1987): 984–89. http://dx.doi.org/10.1182/blood.v69.4.984.bloodjournal694984.
Full textAbstract:
Chromosome aberrations and clinical features of three patients with adult T cell leukemia-lymphoma (ATL) not associated with human T cell leukemia virus type I (HTLV-I) are described. From their clinical features, two patients were diagnosed as acute type and one patient was diagnosed as chronic type, which later converted to acute crisis. Clonal and many chromosomal abnormalities were observed before therapy in the two acute type cases and at relapse in the chronic type case. Karyotype aberrations, including trisomy 3, trisomy 7, trisomy 21, del(6)(q21), del(10)(p13), 14q11 translocation, and loss of X chromosome, all of which are frequently found in HTLV-I associated ATL, were also seen in these cases of HTLV-I-negative ATL.
17
Haferlach, Claudia, Susanne Schnittger, Wolfgang Kern, and Torsten Haferlach. "Myelodysplastic Syndromes and Philadelphia Negative Chronic Myeloproliferative Diseases Show an Overlapping Pattern of Cytogenetic Aberrations." Blood 110, no. 11 (November 16, 2007): 1553. http://dx.doi.org/10.1182/blood.v110.11.1553.1553.
Full textAbstract:
Abstract The WHO classification introduced 3 categories: chronic myeloproliferative diseases (CMPD) myelodysplastic/myeloproliferative diseases (MDS/CMPD) and myelodysplastic syndromes (MDS). The aim was to analyze the pattern of cytogenetic aberrations in these categories excluding CML. In total 1996 cases belonging to these subgroups were referred to our laboratory and analyzed by chromosome banding analysis and cytomorphology. By cytomorphology 438 cases were classified as CMPD, 608 as MDS and 147 as MDS/CMPD. In 350 patients cytomorphology suspected a CMPD (CMPD-s) and in 423 a suspected MDS (MDS-s) but not all requested cytomorphologic criteria were fulfilled in these cases. Chromosome aberrations were detected in 81 of 438 CMPD (18.5%), 232 of 608 MDS (38.2%), 38 of 147 MDS/CMPD (25.9%), 33 of 350 CMPD-s (9.4%) and 71 of 423 MDS-s (16.8%). Therefore, 455 cases showing chromosome aberrations were identified and are the basis for aberration pattern analysis. In all three cytomorphologic categories balanced rearrangements were rare (n=40). The only recurring ones were 3q26-rearrangements (n=4). The most frequent aberrations were +1q (n=22), +8 (n=82, as the sole abnormality n=46), +9p (n=28) and +21 (n=16), i(17)(q10) (n=11), −7 (n=39, as the sole abnormality n=16), and loss of 5q (n=117), 5q deletion as the sole abnormality (n=45), 11q- (n=11), 12p- (n=21), 13q- (n=5), 20q- (n=59, as the sole abnormality n=41), and loss of the Y-chromosome (n=69). A complex aberrant karyotype (≥3 aberrations) was observed in 71 cases. None of these abnormalities was specific for one category. However, the following aberrations were significantly more frequently observed in CMPD as compared to MDS: +1q (10.6% vs 2.6%, p=0.001), +9p (23.0% vs. 0.3%, p<0.0001), +9 sole (8.8% vs. 0.0%. p<0.0001), and balanced rearrangements (15.0% vs. 6.3%. p=0.005). On the other hand the following aberrations were significantly more frequently observed in MDS as compared to CMPD: -Y (18.2% vs. 7.9%. p=0.01), deletion 5q (34.4% vs. 8.8%. p<0.0001), deletion 5q sole (13.9% vs. 2.7%. p=0.001), −7 (9.6% vs. 4.4%. p=0.04), complex aberrant karyotype (18.5% vs. 9.7%. p=0.03). A comparison of the frequencies of abnormalities between MDS/CMPD and CMPD and MDS, respectively, revealed that +8 as the sole abnormality and +21 were significantly more frequent in MDS/CMPD as compared to CMPD or MDS (+8 sole: 21.0% vs 6.2% vs 10.3%, p=0.008 and p=0.05, respectively; +21: 23.6% vs. 0.9% vs 3.3%, p=0.001 and p=0.005, respectively). Deletion 5q and 5q- as the sole abnormality was significantly more frequent in MDS as compared to CMPD/MDS (34.4% vs. 7.9%, p=0.001 and 13.9% vs 0%, p=0.014), while +9 as the sole abnormality was less frequently found in MDS compared to CMPD/MDS (0% vs 2.6%, p=0.005). Trisomy 9p was significantly more frequent in CMPD as compared to CMPD/MDS (23.6% vs. 2.6%, p=0.005), while monosomy 7 as the sole abnormality was less frequently found in CMPD as compared to CMPD/MDS (0.9% vs 7.9%, p=0.02). In conclusion, MDS and CMPD show an overlapping pattern of cytogenetic aberrations with aberrations such as +8, loss of 11q, 12p, 13q and 20q occurring with comparable frequencies. However, trisomy 1q and 9p were observed more frequently in CMPD while -Y, 5q deletion, monosomy 7 and complex aberrant karyotype were predominantly found in MDS. Also from the cytogenetic point of view CMPD/MDS cases are not distinguishable from either MDS or CMPD. However, +21 and +8 as the sole abnormality are more frequently observed in MDS/CMPD as compared to CMPD and MDS.
18
Viardot, Andreas, Peter Möller, Josef Högel, Kirsten Werner, Gunhild Mechtersheimer, Anthony D. Ho, German Ott, et al. "Clinicopathologic Correlations of Genomic Gains and Losses in Follicular Lymphoma." Journal of Clinical Oncology 20, no. 23 (December 1, 2002): 4523–30. http://dx.doi.org/10.1200/jco.2002.12.006.
Full textAbstract:
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.
19
Djordjevic, Vesna, Marija Dencic-Fekete, Jelica Jovanovic, Ivan Soldatovic, Gradimir Jankovic, and Andrija Bogdanovic. "Significance of cytogenetic-risk categories and refined international prognostic scoring system for overall survival in primary myelofibrosis: A single-center experience." Vojnosanitetski pregled 77, no. 5 (2020): 516–24. http://dx.doi.org/10.2298/vsp171129117d.
Full textAbstract:
Abstract Background/Aim. Primary myelofibrosis (PMF) is a chronic, malignant hematological disease characterized by a leucoerythroblastic blood picture, anisopoikilocytosis teardrop- shaped erythrocytes, different degrees of bone marrow fibrosis and hepatosplenomegaly due to extramedullary hematopoiesis. Among genetic specificities of the disease, those that stand out are chromosomal aberrations in pathological, myeloid blood cells. The aim of this study was to examine the prognostic significance of clinical, hematologic and cytogenetic parameters in PMF. Methods. A retrospective study included 144 patients with PMF. Karyotypes were analyzed using conventional cytogenetic methods. Results. The chromosome examinations were successful in 126 (88%) patients and failed in the remainder ones (12%). Karyotype was abnormal in 36/126 (29%) subjects at presentation. The most frequent changes included +9, 13q- and 20q- (28%). Other abnormalities were: aberrations of chromosome 18 and 16, deletions (9q-, 12p-, 7q-, 5q-, 6q-, 8q-), trisomies (+1q, +8, +10, +21), monosomies (-7, -11), 3q inversion and loss of Y chromosome. We detected four novel balanced translocations in PMF: t(17;22)(q11;q13), t(15;17)(q22;q25), t(9;12)(q22;q24) and t(2;4)(q21;p16), one constitutional translocation-rob(13;14)(q10;q10) and some new karyotype anomalies ? deletion of both homologues, hyperdiploidy and the coexistence of unrelated pathological clones. Conclusion. Chromosomal aberrations had a significant influence on overall survival of patients with PMF according to the refined cytogenetic-risk of the International Prognostic Scoring System (Refined CIPSS) (p = 0.004). Our patients matched the pattern of chromosome aberrations usually observed in PMF but some newly registered, balanced translocations and other rare karyotype anomalies were recorded as well.
20
Wrona, Ewa, Marcin Braun, Agata Pastorczak, Joanna Taha, Monika Lejman, Jerzy Kowalczyk, Wojciech Fendler, and Wojciech Młynarski. "MLPA as a complementary tool for diagnosis of chromosome 21 aberrations in childhood BCP-ALL." Journal of Applied Genetics 60, no. 3-4 (August 27, 2019): 347–55. http://dx.doi.org/10.1007/s13353-019-00509-8.
Full text
21
Bugno, Monika, Ewa Słota, Aldona Pieńkowska-schelling, and Claude Schelling. "Identification of chromosome abnormalities in the horse using a panel of chromosome-specific painting probes generated by microdissection." Acta Veterinaria Hungarica 57, no. 3 (September 1, 2009): 369–81. http://dx.doi.org/10.1556/avet.57.2009.3.3.
Full textAbstract:
Fluorescent in situ hybridisation (FISH) using a panel of molecular probes for all chromosome pairs obtained by chromosome microdissection of the domestic horse ( Equus caballus ) was used to diagnose karyotype abnormalities in 35 horses (32 mares, 2 stallions and 1 intersex), which were selected for the study due to infertility (23 horses), reduced fertility (10 horses) and developmental anomalies (2 horses). The use of the FISH technique with probes for each horse chromosome pair enabled the diagnosis of many different chromosome aberrations in this population. Among the horses analysed, 21 animals had normal karyotype — 64,XX (19 mares) and 64,XY (2 stallions). Fourteen animals, constituting 40% of the population studied, showed the following chromosome abnormalities: 63,X (1 mare); 63,X/64,XX (6 mares); 63,X/64,XX/65,XXX (3 mares); 63,X/65,XXX (1 mare); 64,XX/65,XX+Xp (1 mare); 63,X/64,XX/65,XX+Xq (1 mare), and 63,X/64,XX/65,XX+delY (1 intersex). When only the mares studied because of complete infertility were taken into consideration, this proportion exceeded 56%. Due to the increased frequency of the above-mentioned aberrations in the mosaic form of two or more lines, it was necessary to analyse a large number (100–300) of metaphase spreads. The use of specific molecular probes obtained by chromosome microdissection made these diagnoses much easier.
22
Chng, Wee J., Jonathan J. Keats, Esteben Braggio, Angela Baker, P. Leif Bergsagel, John Carpten, and Rafael Fonseca. "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 (November 16, 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.
23
Arnoldus, Edo P. J., Laetitia B. T. Wolters, Joan H. C. Voormolen, Sjoerd G. van Duinen, Anton K. Raap, Mels van der Ploeg, and A. C. Boudewijn Peters. "Interphase cytogenetics: a new tool for the study of genetic changes in brain tumors." Journal of Neurosurgery 76, no. 6 (June 1992): 997–1003. http://dx.doi.org/10.3171/jns.1992.76.6.0997.
Full textAbstract:
✓ Interphase cytogenetics is the application of nonradioactive in situ hybridization with chromosome-specific DNA probes to interphase nuclei. In this study, interphase cytogenetics was used to investigate 66 primary brain tumors (33 gliomas, 30 meningiomas, and three medulloblastomas) for numerical chromosomal aberrations of chromosomes 1, 6, 7, 10, 11, 17, 18, X, and Y. Of the 33 gliomas (17 astrocytomas grades II, III, and IV, five oligoastrocytomas, seven oligodendrogliomas, and four ependymal tumors), 22 were near diploid, while the remaining 11 showed a significant triploid or tetraploid component. The predominant specific aberrations in gliomas were an over-representation of chromosome 7 (13 cases) and an under-representation of chromosome 10 (16 cases), These changes were observed in grade III and grade IV astrocytomas, as well as in oligodendrogliomas. Other frequent numerical changes were a gain of chromosome 17 (six cases) and a loss of chromosome 18 (seven cases). This loss of chromosome 18 seemed relatively specific for gliomas with an oligodendroglial component (six cases). Only two of 33 gliomas displayed no genetic abnormality with the probes used. Seven patients with astrocytomas died of their brain tumor during the clinical follow-up period. Their astrocytomas did not show a different chromosomal constitution compared to the other gliomas. For the meningiomas, the probe panel was extended with a probe specific for chromosome 22. Loss of chromosome 22 was obvious in 21 of the 30 meningiomas, and was the sole abnormality in 11 meningiomas; in the other 10, this loss was associated with other chromosomal changes. Five of these tumors with additional aberrations were recurrent or atypical meningiomas. It is suggested that interphase cytogenetics can contribute to a better understanding of the biological behavior of these tumors and possibly result in better insights into prognosis and strategies for therapy.
24
Hernandes, Marina Araújo Fonzar, Terezinha de Jesus Marques-Salles, Hasmik Mkrtchyan, Eliane Maria Soares-Ventura, Edinalva Pereira Leite, Maria Tereza Cartaxo Muniz, Maria Teresa Marquim Nogueira Cornélio, Thomas Liehr, Neide Santos, and Maria Luiza Macedo Silva. "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.
25
Miura, Makoto, Isamu Sando, Shin-Ichi Haginomori, Carey D. Balaban, and Yorihisa Orita. "Temporal Bone Morphometric Study on the Eustachian Tube and its Associated Structures in Patients with Chromosomal Aberrations." Annals of Otology, Rhinology & Laryngology 111, no. 8 (August 2002): 722–29. http://dx.doi.org/10.1177/000348940211100812.
Full textAbstract:
This study characterized phenotypic anomalies of the eustachian tube (ET) and its associated structures in individuals with various chromosomal aberrations (trisomies 13, 18, 21, and 22 and inversion of chromosome 1). The morphological characteristics of the ET and its accessory structures from 10 temporal bone-ET specimens, obtained from 10 individuals with chromosomal aberrations who ranged from the 26th gestational week to 1 year in age, were compared with the same structures from 21 age-matched control subjects without anomalies. The subjects with chromosomal aberrations had a significantly smaller volume of the lateral lamina (LL) of the ET cartilage, a reduced attachment of the tensor veli palatini muscle (TVPM), and, in some cases, a reduced volume of the lumen of the cartilaginous ET. The volume of the medial lamina (ML) of the ET cartilage was normal at birth, but smaller in specimens more than 2 months of age; this finding suggests that the prenatal development was normal, but that the postnatal growth was retarded. The subjects with chromosomal aberrations also displayed a smaller ratio of the volume of the LL to that of the ML (LL/ML ratio). Our results suggest that individuals with various chromosomal aberrations have rather similar anomalies of the ET and its associated structures. We speculate that these anomalies might be closely related to ET dysfunction in these patients.
26
Iannuzzi, Alessandra, Viviana Genualdo, Angela Perucatti, Alfredo Pauciullo, Giovanna Varricchio, Domenico Incarnato, Donato Matassino, and Leopoldo Iannuzzi. "Fatal Outcome in a Newborn Calf Associated with Partial Trisomy 25q and Partial Monosomy 11q, 60,XX,der(11)t(11;25)(q11;q14∼21)." Cytogenetic and Genome Research 146, no. 3 (2015): 222–29. http://dx.doi.org/10.1159/000438973.
Full textAbstract:
A newborn calf of the Agerolese cattle breed underwent clinical cytogenetic investigation because of hyperflexion of the forelimbs, red eyes and the inability to stand. Anamnesis revealed that the mother, phenotypically normal, carried a chromosomal aberration. The newborn died after 2 weeks, and no remarkable alterations were found by the veterinarian on postmortem examination. The mother was a carrier of a reciprocal balanced translocation rcp(11;25)(q11,q14∼21) detected after a cytogenetic investigation in 2011; however, the analysis of the newborn revealed a different chromosomal aberration with partial trisomy of chromosome 25 and partial monosomy of chromosome 11. In fact, the results showed both chromosomes 25, one chromosome 11 and only one long derivative chromosome (der11). FISH analysis, performed using BAC clones, confirmed the chromosomes and their regions involved. Finally, both the localization of the breakpoints on band q11 (centromere) of chromosome 11 and band q14-21 of chromosome 25, and the complete loss of the der25 identified the aberration as an unbalanced translocation 60,XX,der(11)t(11;25)(q11;q14∼21). A comparison with human chromosomes was also performed to search for similarities and possible genes involved in order to study their effects, thus extending the knowledge of these aberrations by case reports.
27
Pedersen-Bjergaard, J., M. Pedersen, D. Roulston, and P. Philip. "Different genetic pathways in leukemogenesis for patients presenting with therapy-related myelodysplasia and therapy-related acute myeloid leukemia." Blood 86, no. 9 (November 1, 1995): 3542–52. http://dx.doi.org/10.1182/blood.v86.9.3542.bloodjournal8693542.
Full textAbstract:
Development of myelodysplasia (MDS) with subsequent progression to acute myeloid leukemia (AML) is an example of the multistep process of malignant transformation in which each step often relates to genetic abnormalities that can be directly seen as chromosomal aberrations. Therapy-related MDS and AML (t-MDS and t-AML) may serve as an ideal model for a study of the genetic evolution of MDS and AML because chromosomal abnormalities are observed in most cases and because the disease is often diagnosed early due to a close patient follow-up. The cytogenetic characteristics at diagnosis were studied in 137 consecutive cases of t-MDS and t-AML, including 22 new cases, and correlated with the clinical characteristics and the course of the disease. Balanced translocations to chromosome bands 11q23 and 21q22 represent primary steps in pathways leading directly to overt t-AML. Specific chromosomal deletions or losses, on the other hand, represent primary or secondary events in alternative pathways leading to t-MDS with potential for subsequent transformation to overt t-AML. Loss of a whole chromosome 7 (-7) or deletion of its long arm (7q-) and deletion of the long arm of a chromosome 5 (5q-) were the most frequent primary abnormalities significantly related to t-MDS. Loss of a whole chromosome 5 (-5) was also a primary event, but surprisingly, was observed equally in t-MDS and in t-AML. Deletion of chromosome 13, including bands q13q14, was another less common primary aberration of t- MDS. Except for -7 and del(13q), these primary aberrations were most often observed together with secondary abnormalities. These included balanced aberrations involving band 3q26 and various deletions of chromosome 3, a gain of a whole chromosome 8, deletions of the short arm or loss of chromosomes 12 and 17, loss of a whole chromosome 18, and deletions of the short arm of chromosome 21. Deletions or loss or chromosomes 5 and 7 were significantly associated with previous therapy with alkylating agents (P = .002), and balanced translocations to chromosome bands 3q26, 11q23, and 21q22 were significantly associated with previous therapy with drugs targeting DNA-topoisomerase II (P < .00005). Other characteristic aberrations were not related to any specific type of therapy. The molecular changes believed to contribute to the development of t-MDS and t-AML have been identified for many of these chromosomal abnormalities.
28
Grigorova, M., and A. T. Natarajan. "Relative involvement of chromosome #21 in radiation induced exchange aberrations in lymphocytes of down syndrome patients." Mutation Research/Fundamental and Molecular Mechanisms of Mutagenesis 404, no. 1-2 (August 1998): 67–75. http://dx.doi.org/10.1016/s0027-5107(98)00096-7.
Full text
29
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 (November 16, 2005): 1192. http://dx.doi.org/10.1182/blood.v106.11.1192.1192.
Full textAbstract:
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.
30
Metzger, Andrew K., Gayatry Mohapatra, Yuriko A. Minn, Andrew W. Bollen, Kathleen Lamborn, Frederic M. Waldman, Charles B. Wilson, and Burt G. Feuerstein. "Multiple genetic aberrations including evidence of chromosome 11q13 rearrangement detected in pituitary adenomas by comparative genomic hybridization." Journal of Neurosurgery 90, no. 2 (February 1999): 306–14. http://dx.doi.org/10.3171/jns.1999.90.2.0306.
Full textAbstract:
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.
31
Zemanova, Zuzana, Kyra Michalova, Libuse Babicka, Lenka Pavlistova, Marie Jarosova, Milena Holzerova, Alexandra Oltova, 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 (November 1, 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.
32
D'Alessandro, Elvira, Maria Luisa Lo Re, Roberto Crisci, Claudio Ligas, and Giorgio Furio Coloni. "Cytogenetic Findings in Primary Non-Small Cell Lung Cancer." Tumori Journal 80, no. 2 (April 1994): 151–56. http://dx.doi.org/10.1177/030089169408000214.
Full textAbstract:
Non-small cell lung cancer (NSCLC) shows a complex cytogenetic heterogeneity and up to now no particular chromosomal aberration seems to characterize its malignant evolution. We therefore performed cytogenetic analyses of 20 primary NSCLC, 8 adenocarcinomas and 12 squamous cell carcinomas on direct preparations or short-term cultures. Only 1 case was analyzed after long-term culture. Results were obtained from 11 samples and clonal rearrangements were found in 3 cases, a diploid and a near-triploid clone with several aberrations such as i (9q), rob (14; 15) and rob (21; 21) in 1 case, a near-triploid clone in 1 case, and Y chromosome loss in 1 case. Other aberrations found were sporadic, but + 7 aneuploidy and translocations involving 1p were detected in 2 and 3 samples respectively. Although to date it has been very difficult to recognize primary changes in NSCLC, nevertheless a literature review and our results indicate that i(9q) and robertsonian translocations are relevant findings.
33
Schwaenen, Carsten, Swen Wessendorf, Andreas Viardot, Sandra Ruf, Martina Enz, Holger Kohlhammer, Hans A. Kestler, et al. "High Resolution Screening of Genomic Aberrations in Follicular Lymphoma Using Microarray Based Comparative Genomic Hybridization (MATRIX-CGH)." Blood 104, no. 11 (November 16, 2004): 2271. http://dx.doi.org/10.1182/blood.v104.11.2271.2271.
Full textAbstract:
Abstract Follicular Lymphoma (FL), one of the most frequent lymphoma entities in the western world, is characterized by a highly variable clinical course reaching from rapid progression with fatal outcome to cases with long term survival. In a recent study applying chromosomal comparative hybridization (CGH) to FL, in 70% of the cases genomic aberrations were detectable and a loss of genomic material on chromosomal bands 6q25-q27 was the strongest predictor for short overall survival. However, limitations of CGH as a screening method are a restricted genomic resolution to 3–10 Mbp and demanding non-automated evaluation procedures. Thus, high throughput analysis of genomic alterations for risk adapted patient stratification and monitoring within treatment trials should rely on efficient and automated diagnostic techniques. In this study, we used array CGH to a novel generation of DNA Chips containing 2800 genomic DNA probes. Target clones comprised i) contigs mapping to genomic regions of possible pathogenetic relevance in lymphoma (n=610 target clones mapping to e.g. 1p, 2p, 3q, 7q, 9p, 11q, 12q, 13q, 17p, 18q, X); ii) selected oncogenes and tumor suppressor genes (n=686) potentially relevant in hematologic neoplasms; and iii) a large genome-wide cluster of 1502 target DNA clones covering the genome at a distance of app. 2 Mbp (part of the golden path clone set). This chip represents a median genomic resolution of app. 1.5 Mbp. In total, DNAs from 70 FL samples were analyzed and results were compared to data from chromosomal CGH experiments and clinical data sets. The sensitivity of array CGH was considerably higher compared to chromosomal CGH (aberrations in 95% of cases vs 70% of cases). Most frequent aberrations were gain mapping to chromosome arms 2p (21%), 7p (24%), 7q (30%), 12p (17%), 12q (21%), 18p (21%) and 18q (34%) as well as losses mapping to chromosome arms 1p (19%), 6q (23%), 7p (20%), 11q (26%) and 17p (20%). In addition, several genomic aberrations were identified which have not been described before in FL. Currently, these aberrations are characterized in more detail and results will be correlated with the clinical data set. Moreover, three recurrent sites of genomic polymorphisms in human beings affecting chromosomes 5q, 14q and 15q were identified. In conclusion, these data underline the potential of array CGH for the sensitive detection of genomic imbalances in FL.
34
Pazarbasi, A., O. Demirhan, D. Alptekin, Ft Ozgunen, L. Ozpak, Mb Yilmaz, E. Nazlican, N. Tanriverdi, U. Luleyap, and D. Gümürdülü. "INHERITANCE OF A CHROMOSOME 3 AND 21 TRANSLOCATION IN THE FETUSES, WITH ONE ALSO HAVING TRISOMY 21, IN THREE PREGNANCIES IN ONE FAMILY." Balkan Journal of Medical Genetics 16, no. 2 (December 1, 2013): 91–96. http://dx.doi.org/10.2478/bjmg-2013-0039.
Full textAbstract:
ABSTRACT The majority of chromosome rearrangements are balanced reciprocal and Robertsonian translocations. It is now known that such abnormalities cause no phenotypic effect on the carrier but lead to increased risk of producing unbalanced gametes. Here, we report the inheritance of a translocation between chromosomes 3 and 21 in a family with one of two fetuses with Down Syndrome carrying the same translocation and the other also carrying the same translocation without the additional chromosome 21. Chromosomal analysis from fetal amniotic fluid and peripheral blood lymphocytes from the family were performed at the Çukurova University Hospital at Adana, Turkey. We assessed a family in which the translocation between chromosomes 3 and 21 segregates: one of the three progenies carried the 47,XX,+21,t(3;21)(q21;q22) karyotype and presented with Down Syndrome; another of the three progenies carried the 46,XX,t(3;21) (q21;q22) karyotype and the third had the 46,XY karyotype. Their mother is phenotypically normal. Apparently this rearrangement occurred due to an unbalanced chromosome segregation of the mother [t(3;21)(q21;q22)mat]. This family will enable us to explain the behavior of segregation patterns and the mechanism for each type of translocation from carrier to carrier and their effects on reproduction and numerical aberrations. These findings can be used in clinical genetics and may be used as an effective tool for reproductive guidance and genetic counseling
35
Bartholomei-Santos, Marlise Ladvocat, and Edmundo José de Lucca. "Chromosome sensitivity to bleomycin in G2 lymphocytes from Down syndrome patients." Brazilian Journal of Genetics 20, no. 1 (March 1997): 79–85. http://dx.doi.org/10.1590/s0100-84551997000100015.
Full textAbstract:
Several studies have demonstrated that lymphocytes from patients with Down syndrome (DS) exhibit an increased frequency of chromosome aberrations when they are exposed to ionizing radiation or to chemicals at the G0 or G1 phases of the cell cycle, but not at G2, when compared to normal subjects. To determine the susceptibility of DS lymphocytes at G2 phase, bleomycin, a radiomimetic agent, was used to induce DNA breaks in blood cultures from 24 Down syndrome patients. All the patients with DS showed free trisomy 21 (47,XX + 21 or 47,XY + 21). Individuals that showed an average number of chromatid breaks per cell higher than 0.8 were considered sensitive to the drug. No control child showed susceptibility to bleomycin, and among the 24 patients with DS, only one was sensitive to the drug. No significant difference was observed between the two groups, regarding chromatid break frequencies in treated G2 lymphocytes. The distribution of bleomycin-induced breaks in each group of chromosomes was similar for DS and controls. No significant difference was found in the response to bleomycin between male and female subjects. Probably, the main factor involved in chromosome sensitivity of lymphocytes from patients with DS is the phase of the cell cycle in which the cell is treated.
36
Livingston, Gordon K., Maria Escalona, Alvis Foster, and Adayabalam S. Balajee. "Persistent in vivo cytogenetic effects of radioiodine therapy: a 21-year follow-up study using multicolor FISH." Journal of Radiation Research 59, no. 1 (September 26, 2017): 10–17. http://dx.doi.org/10.1093/jrr/rrx049.
Full textAbstract:
Abstract Our previous studies demonstrated the cytogenetic effects in the peripheral blood lymphocytes of a 34-year-old male patient who received ablative radioactive 131iodine therapy (RIT) on two different occasions in 1992 and 1994. Assessment of RIT-induced chromosomal damage by the cytokinesis-blocked micronucleus assay (CBMN) showed the persistence of elevated micronucleus frequency in this patient for more than two decades since the first RIT. Subsequent cytogenetic analysis performed in 2012 revealed both stable and unstable aberrations, whose frequencies were higher than the baseline reported in the literature. Here, we report the findings of our recent cytogenetic analysis peformed in 2015 on this patient using the multicolor fluorescence in situ hybridization (mFISH) technique. Our results showed that both reciprocal and non-reciprocal translocations persisted at higher frequencies in the patient than those reported in 2012. Persistence of structural aberrations for more than two decades indicate that these aberrations might have originated from long-lived T-lymphocytes or hematopoietic stem cells. Our study suggests that the long-term persistence of chromosome translocations in circulating lymphocytes can be useful for monitoring the extent of RIT-induced chromosomal instability several years after exposure and for estimating the cumulative absorbed dose after multiple RITs for retrospective biodosimetry purposes. This is perhaps the first and longest follow-up study documenting the persistence of cytogenetic damage for 21 years after internal radiation exposure.
37
Hasle, Henrik, Todd A. Alonzo, Anne Auvrignon, Catherine Behar, Myron Chang, Ursula Creutzig, Alexandra Fischer, et al. "Monosomy 7 and deletion 7q in children and adolescents with acute myeloid leukemia: an international retrospective study." Blood 109, no. 11 (June 1, 2007): 4641–47. http://dx.doi.org/10.1182/blood-2006-10-051342.
Full textAbstract:
Abstract Monosomy 7 (−7) and deletion 7q \del(7q)] are rare in childhood acute myeloid leukemia (AML). We retrospectively collected data on 258 children with AML or refractory anemia with excess blasts in transformation (RAEB-T) and −7 or del(7q) with or without other cytogenetic aberrations \± other]. Karyotypes included −7 (n = 90), −7 other (n = 82), del(7q) (n = 21), and del(7q) other (n = 65). Complete remission (CR) was achieved in fewer patients with −7 ± other compared with del(7q) ± other (61% versus 89%, P < .001). Overall, the 5-year survival rate was 39% (SE, 3%). Survival was superior in del(7q) ± other compared with −7 ± other (51% versus 30%, P < .01). Cytogenetic aberrations considered favorable in AML \t(8;21)(q22;q22), inv(16)(p13q22), t(15;17)(q22;q21), t(9;11)(p22;q23)] (n = 24) were strongly associated with del(7q) and a higher 5-year survival rate compared with del(7q) without favorable cytogenetics (75% versus 46%, P = .03). Patients with −7 and inv(3),−5/del(5q), or + 21 had a 5-year survival rate of 5%. Stem cell transplantation analyzed as a time-dependent variable had no impact on overall survival. However, patients not achieving CR had a 31% survival rate after stem cell transplantation. Childhood AML with chromosome 7 aberrations represents a heterogeneous group of disorders with additional cytogenetic aberrations having a major prognostic impact which should be reflected in future risk-group stratification.
38
Saraswathy, Radha, and A. T. Natarajan. "Frequencies of X-ray induced chromosome aberrations in lymphocytes of xeroderma pigmentosum and Fanconi anemia patients estimated by Giemsa and fluorescence in situ hybridization staining techniques." Genetics and Molecular Biology 23, no. 4 (December 2000): 893–99. http://dx.doi.org/10.1590/s1415-47572000000400031.
Full textAbstract:
Blood lymphocytes from xeroderma pigmentosum (XP) and Fanconi anemia (FA) patients were assessed for their sensitivity to ionizing radiation by estimating the frequency of X-ray (1 and 2 Gy)-induced chromosome aberrations (CA). The frequencies of aberrations in the whole genome were estimated in Giemsa-stained preparations of lymphocytes irradiated at G0 or G2 stages. The frequencies of translocations and dicentrics involving chromosomes 1 and 3 as well as the X-chromosome were determined in slides stained by fluorescence in situ hybridization (FISH) technique. An increase in all types of CA was observed in XP and FA lymphocytes irradiated at G0 when compared to controls. The frequency of dicentrics and rings was 6 to 27% higher (at 1 and 2 Gy) in XP lymphocytes and 37% higher (at 2 Gy) in FA lymphocytes than in controls, while chromosome deletions were higher in irradiated (30% in 1 Gy and 72% in 2 Gy) than in control XP lymphocytes and 28 to 102% higher in FA lymphocytes. In G2-irradiated lymphocytes the frequency of CA was 24 to 55% higher in XP lymphocytes than in controls. In most cases the translocation frequencies were higher than the frequencies of dicentrics (21/19).
39
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 (March 1, 1998): 1732–41. http://dx.doi.org/10.1182/blood.v91.5.1732.
Full textAbstract:
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.
40
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 (March 1, 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.
41
Haferlach, Claudia, Cristina Mecucci, Susanne Schnittger, Alexander Kohlmann, Marco Mancini, Antonio Cuneo, Nicoletta Testoni, et al. "AML with mutated NPM1 carrying a normal or aberrant karyotype show overlapping biologic, pathologic, immunophenotypic, and prognostic features." Blood 114, no. 14 (October 1, 2009): 3024–32. http://dx.doi.org/10.1182/blood-2009-01-197871.
Full textAbstract:
Acute myeloid leukemia (AML) with mutated NPM1 usually carries normal karyotype (NK), but it may harbor chromosomal aberrations whose significance remains unclear. We addressed this question in 631 AML patients with mutated/cytoplasmic NPM1. An abnormal karyotype (AK) was present in 93 of 631 cases (14.7%), the most frequent abnormalities being +8, +4, −Y, del(9q), +21. Chromosome aberrations in NPM1-mutated AML were similar to, but occurred less frequently than additional chromosome changes found in other AML with recurrent cytogenetic abnormalities according to WHO classification. Four of the 31 NPM1-mutated AML patients karyotyped at different time points had NK at diagnosis but AK at relapse: del(9q) (n = 2), t(2;11) (n = 1), inv(12) (n = 1). NPM1-mutated AML with NK or AK showed overlapping morphologic, immunophenotypic (CD34 negativity), and gene expression profile (down-regulation of CD34 and up-regulation of HOX genes). No difference in survival was observed among NPM1-mutated AML patients independently of whether they carried a NK or an AK, the NPM1-mutated/FLT3-ITD negative cases showing the better prognosis. Findings in our patients point to chromosomal aberrations as secondary events, reinforce the concept that NPM1 mutation is a founder genetic lesion, and indicate that NPM1-mutated AML should be clinically handled as one entity, irrespective of the karyotype.
42
Göhring, Gudrun, Caroline Fedder, Kathrin Lange, Andrea Schienke, Winfried Hofmann, Hans H. Kreipe, and Brigitte Schlegelberger. "Telomere Shortening and Chromosomal Instability in Chronic Lymphocytic Leukemia." Blood 118, no. 21 (November 18, 2011): 1761. http://dx.doi.org/10.1182/blood.v118.21.1761.1761.
Full textAbstract:
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.
43
Kern, Wolfgang, Frank Dicker, Torsten Haferlach, Susanne Schnittger, and Claudia Haferlach. "Pattern of Chromosomal Aberrations and IgVH Mutation Status in Patients with Monoclonal B-Cell Lymphocytosis (MBL)." Blood 112, no. 11 (November 16, 2008): 3142. http://dx.doi.org/10.1182/blood.v112.11.3142.3142.
Full textAbstract:
Abstract The separation between chronic lymphocytic leukemia (CLL) and monoclonal B-cell lymphocytosis (MBL) with CLL-phenotype by the presence of more than 5,000/μl lymphocytes in peripheral blood has been debated due to the rather continuous spectrum of clinical and biological features of both entities. Furthermore, this separation is influenced by non-malignant cells since it is based on the total lymphocyte count and not only on the count of cells with CLL-phenotype. To broaden the insights into the genetic background of MBL at the boarder to CLL we analyzed 188 cases with less than 5,000/μl CLL-phenotype cells for chromosomal aberrations by fluorescence in situ hybridization (FISH) using a standard panel of probes as well as for their IgVH mutation status. In addition, in 116 of these cases conventional chromosome analysis has been performed. Patient characteristic were (median/range): age, 66.0/27.5–86.6 years; WBC count, 10,600/1,700–22,660/μl; cells with CLL-phenotype 26/4-94% and 3,081/264–4,998/μl, respectively. The proportion of aberrant/analyzed cases for the respective chromosome aberrations as determined by FISH were: 11q-, 10/182 (5.5%); +12, 39/183 (21.3%); 6q-, 2/182 (1.1%); 13q-, 88/185 (47.6%); 17p-, 3/183 (1.6%); and t(11;14), 8/183 (4.4%). In 57/185 (30.8%) cases no aberration was found by FISH. A comparison to a previous series of 518 CLL cases revealed similar frequencies for +12, 6q-, and t(11;14) but higher frequencies in CLL for 11q-, 5.5 vs. 13.1%, p=0.004; 13q-, 47.6 vs. 57.8%, p=0.020; and 17p-, 1.6 vs. 8.1%, p=0.001. Within the present series, a relation between the respective chromosome aberration and the count of cells with CLL-phenotype was found for 6q- vs. no 6q-, 1,214 vs. 2,910/μl, p=0.079; 13q- vs. no 13q-, 3,285 vs. 2,486/μl, p<0.001; t(11;14) vs. no t(11;14), 2,025 vs. 2,920/μl, p=0.087 but not for 11q-, +12, and 17p- aberrations. IgVH mutation status has been analyzed in 172 cases and was found unmutated (IgVHunmut) in 44 (25.6%) und mutated (IgVHmut) in 111 (64.5%). No clonal IgVH rearrangement was detectable in 17 (9.9%). A relation to the count of cells with CLL-phenotype was found: IgVHmut vs. IgVHunmut, 3,071 vs. 2,629/μl, p=0.052. Conventional chromosome analysis has been performed in addition in 116 of these cases resulting in 111 (95.7%) evaluable cases. In general, results obtained by FISH were confirmed: 11q-, n=3 (1.8%); +12, n=21 (21.3%); 6q- 1 (0.9%); 13q-, n=39 (35.1%), and t(11;14), n=5 (4.5%). Additional aberrations were found and included other trisomies (n=13), other balanced translocations/inversions (n=13), 14q- (n=8), loss of sex chromosome (n=3), t(14;18) (n=1), and 2q- (n=1). Thus, a total of 39 chromosome aberrations have been found in 111 cases as assessed by conventional chromosome analysis which could not be detected by FISH using a standard panel of probes. In 30 cases (27%) a normal karyotype was found. These data indicate that the genetic background of MBL is highly related to the one of classical CLL as defined today although 11q-, 13q- and 17p- occur more frequently in CLL. Chromosome aberrations are present in clearly more than half of the cases and an unmutated IgVH status can be detected in a quarter of cases. Similar to CLL, conventional chromosome analysis reveals a substantial number of aberrations not detectable by FISH using a standard panel of probes. It is suggested to further analyze the genetic spectrum of MBL and early CLL cases and its clinical impact and to challenge based on these data the rather arbitrarily defined cut-off values like 5,000/μl lymphocytes.
44
Kobierzyńska, Z. "On the effects of secretions of saprophytic bacteria on the course of mitosis in adventitious roots of Allium cepa L." Acta Societatis Botanicorum Poloniae 42, no. 1 (2015): 171–79. http://dx.doi.org/10.5586/asbp.1973.011.
Full textAbstract:
The influence of 21 strains of saprophytic bacteria isolated from onion cultures on the course of mitosis and on the level of chromosome aberrations in adventitious roots of <i>Allium cepa</i> L. was studied. Liquid cultures of all bacterial strains caused no changes in divisions of the cells. However, ten of the strains were responsible for disturbances in this process. The nature of these disturbances depended to a large extent on the kind of medium in which the bacteria were grown.
45
Sawyer, Jeffrey R., Charles M. Swanson, Janet L. Lukacs, Richard W. Nicholas, Paula E. North, and James R. Thomas. "Evidence of an association between 6q13-21 chromosome aberrations and locally aggressive behavior in patients with cartilage tumors." Cancer 82, no. 3 (February 1, 1998): 474–83. http://dx.doi.org/10.1002/(sici)1097-0142(19980201)82:3<474::aid-cncr8>3.0.co;2-p.
Full text
46
Mantovani, Vilma, Elisabetta Dondi, Daniela Larizza, Mariangela Cisternino, Michela Bragliani, Mariagabriella Viggiani, Miryam Martinetti, and Mariaclara Cuccia. "Do reduced levels of steroid 21-hydroxylase confer a survival advantage in fetuses affected by sex chromosome aberrations?" European Journal of Human Genetics 10, no. 2 (February 2002): 137–40. http://dx.doi.org/10.1038/sj.ejhg.5200778.
Full text
47
Milicevic, Radovan, Ljiljana Brankovic, Desanka Radulovic, Dragana Jugovic, Hristina Stamenkovic, Tatjana Stankovic, Aleksandar Milicevic, Visnja Madic, and Marina Ristic. "Fetal chromosomal anomalies in southeast Serbia - single center cohort retrospective study." Genetika 51, no. 1 (2019): 157–66. http://dx.doi.org/10.2298/gensr1901157m.
Full textAbstract:
Congenital anomalies are the cause of prenatal death in 20-25% of the cases, while 3% of children are born with a malformation of varying size. Many of these anomalies can be detected before birth using different non-invasive and invasive prenatal diagnostic tests. This study was used to determine the distribution of genetic disorders in relation to the age of the mother, the frequency of aberrations and to study the effects and importance of prenatal diagnosis in South Serbia. Prenatal diagnostics was performed at the Pediatric Clinic within the Clinical Center of Nis. This retrospective study included a group of 8830 pregnant women, aged between 18 and 47 years during the period from 2004 to 2017. Amniocentesis was performed between the 16th and 18th week of pregnancy and involved the aspiration of 20 ml of amniotic fluid. Isolated cells were cultured in a medium that stimulates cell growth for 10 days. After cytogenetic processing, the obtained karyotype was analyzed using G-banding techniques. In 8830 samples of amniotic fluid cell cultures, 198 karyotypes with chromosomal aberrations were found - 179 with numerical aberrations and 19 with structural aberrations such as translocations, inversions and deletions. There were 85 karyotypes with autosomal numerical aberrations and 32 karyotypes with sex chromosome numerical aberrations. The most frequent one was trisomy 21 (106 cases). The highest number of autosomal numerical aberrations, 84%, was found in pregnancies where maternal age was above 30 years. Preventive action, advice, education and availability of prenatal diagnosis can lead to a significant reduction in the number of children born with various malformations.
48
Li, Jianyong, Jinlan Pan, Bing Xiao, Li Ma, Hairong Qiu, Li Li, Wei Xu, Yongquan Xue, and Changgeng Ruan. "Multiplex Fluorescence In Situ Hybridization (M-FISH) in the Detection of Complex Karyotypic Abnormalities of Acute Myeloid Leukemia and Myelodysplastic Syndromes." Blood 106, no. 11 (November 16, 2005): 4504. http://dx.doi.org/10.1182/blood.v106.11.4504.4504.
Full textAbstract:
Abstract The complex chromosome abnormalities (CCAs) were one of the most important poor prognostic risk factors in acute myeloid leukemia (AML) and myelodysplastic syndromes (MDS). Chromosome analysis using classical cytogenetic banding techniques fails to completely resolve complex karyotypes and cryptic translocations. The technique of multiplex fluorescence in situ hybridization (M-FISH) allow for the simultaneous visualization of all chromosomes of a metaphase in a single hybridization step and thereby enable to comprehensively analyze complex karyotypes and the identification of new and cryptic translocations. To investigate the value of M-FISH in the detection of complex karyotypic abnormalities of AML and MDS. M-FISH was used in combination with interphase-FISH to study 24 cases of AML and MDS with CCAs showed by R-banding of conventional cytogenetics (CC). In 14 cases of AML with CCAs, 4 gains of whole chromosome and 4 losses of whole chromosome were confirmed by M-FISH, while 12 losses of whole chromosome were revised as derivative chromosomes resulted from various structural aberrations. 26 derivative chromosomes and 19 marker chromosomes were characterized precisely by M-FISH. Most of them were unbalanced translocations, including 2 complex t(8;21), which have not been previously described:t(8;21), der(8) t(8;21) (8pter→8q22::21q22→21qter), der(21) t(8;21;8) (8qter→ 8q22::21p13→ 21q22::8q22→ 8qter) and t(21;8;18;1), der(8) t(8;21) (8pter→ 8q22::21q22→ 21qter), der(21) t(21;8;18;1) (21p13→ 21q22::8q22→ 8q24::18?::1q?q?). In 10 cases of MDS, 37 kinds of structural rearrangements were detected by M-FISH including insertion, deletion, translocation and derivative chromosomes, and among them 34 kinds were unbalanced rearrangements, only 3 were balanced rearrangements including t(6;22)(q21;q12), t(9;19)(q13;p13) and t(3;5)( ?;?), 7 abnormalities were never reported before. The CCAs invloved nearly all chromosomes, of which the chromosome 17, 5 and 7 were invloved more frequent than the rest. Chromosomes 5, 17, 7 were involved in 15 cases (62.5%), 12 cases (50%) and 6 cases (25%) respecrively. We conclude that M-FISH could refine CCAs of AML and MDS patients, find or correct the missed or misidentified aberrations by CC analysis. Our findings confirm that M-FISH is a powerful tool to characterize complex karyotypes in AML and MDS.
49
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 (November 16, 2012): 522. http://dx.doi.org/10.1182/blood.v120.21.522.522.
Full textAbstract:
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.
50
Chakraborty, Sujata, Smita Bhatia, Stephen J. Forman, and Ravi Bhatia. "Mechanisms of Susceptibility to 11q23 MLL Gene Locus Rearrangements in CD34+ Cells Exposed to Etoposide." Blood 114, no. 22 (November 20, 2009): 185. http://dx.doi.org/10.1182/blood.v114.22.185.185.
Full textAbstract:
Abstract Abstract 185 Exposure to the topoisomerase II inhibitor etoposide (VP16) is a significant risk factor in the development of t-MDS/AML. VP16 induces a variety of chromosomal lesions, with the most prominent ones involving the Mixed Lineage Leukemia (MLL) gene on chromosome 11q23. The MLL gene is essential for the maintenance of adult hematopoietic stem cells (HSCs) and progenitors. It is not clear whether the high frequency of MLL gene rearrangements in VP16-treated patients represents increased susceptibility of this locus to VP16-induced damage or a growth advantage of MLL-rearranged hematopoietic progenitors. In the present study we investigated the following: i) the sequence of acquisition of chromosomal lesions in normal CD34+ cells following in vitro exposure to VP16; ii) the specific propensity for development of lesions in 11q23 MLL locus; iii) and the fate of these lesions over time. CD34+ cells were selected from peripheral blood stem cell samples obtained from normal donors (n=5); they were exposed to increasing doses of VP16 (0-40 μM) for 4 hours; washed and cultured in serum-free medium containing growth factors; and assessed for apoptosis, colony forming cell (CFC) assay and chromosomal damage. Chromosome painting was performed using whole chromosome probes for chromosomes 1, 5, 7, 11 and 21, covering 25.2% of total genomic DNA with >100 metaphases scored per dose per time point. Evaluations were performed after 72 hours of culture, representing the 1st cell division after VP16 exposure, and after 144 hours representing 3-4 cell divisions. A dose-dependant decrease in colony formation (71.52 ± 0.99% of controls with 5 mM VP16, and 33.62 ± 4.4%%, with 20 mM VP16 at 72h, p<0.001), and increase in apoptosis (9.12 ± 1.67% with 5 mM VP16, and 39.3 ± 5.06 with 20 mM VP16 at 72h, p<0.001) was observed. The percentage of aberrant metaphases at 1st division was 2.4% with 5 μM and 14.9% with 20 μM of VP16. Both stable aberrations (translocations) and unstable (dicentrics, fragments) aberrations were observed. The percentage of aberrant metaphases was reduced after 3-4 cell divisions (1.4% with 5 μM and 8.7% with 20 μM VP16), and only stable aberrations were present whereas unstable aberrations were eliminated. A higher frequency of aberrations was observed in chromosome 11 compared to the other chromosomes. A 1.5- to 4-fold increase in stable lesions of chromosome 11 relative to other chromosomes was seen at the 1st division and a 2- to 3-fold increase relative to other chromosomes was seen after 3-4 divisions. To assess whether the 11q23 MLL locus was specifically affected by VP16 treatment, we performed interphase FISH with a break-apart probe for the MLL gene (11q23). A break-apart probe for the MYC gene (8q24) was studied as a control. Cells were cultured for three weeks. In preliminary experiments we observed that a higher percentage of cells showed 11q23 abnormalities (9.3%) compared with 8q24 abnormalities (5.4%) at the 1st division. 11q23 abnormalities persisted at high levels in cells (9.9%) cultured for 3 weeks. In contrast, 8q24 abnormalities were markedly reduced (0.4%) after 3 weeks of culture, suggesting selective maintenance of MLL-rearranged cells in culture. In conclusion we show that in vitro exposure to VP16 results in a dose-dependent induction of both stable and unstable chromosomal aberrations in CD34+ hematopoietic progenitors. We observe persistence of stable chromosomal aberrations with particular predisposition to aberrations in chromosome 11. Our results suggest a selective predisposition to 11q23 MLL locus rearrangements that appears to be related to enhanced susceptibility to damage to this locus following VP16 exposure as well as selective maintenance of MLL rearranged cells over subsequent cell divisions. These findings are now being applied to understand the relationship between individual susceptibility to acquisition of VP16-induced 11q23 abnormalities in CD34+ cells and risk of development of t-MDS/AML. Disclosures: No relevant conflicts of interest to declare.