To see the other types of publications on this topic, follow the link: Optical genome mapping (OGM).
Journal articles on the topic 'Optical genome mapping (OGM)'
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 'Optical genome mapping (OGM).'
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
Ruby Dhar, Arun Kumar, and Subhradip Karmakar. "Optical Genome Mapping ( OGM) : Looking beyond karyotyping." Asian Journal of Medical Sciences 16, no. 1 (2025): 1–2. https://doi.org/10.71152/ajms.v16i1.4353.
Full textAbstract:
Optical genome mapping (OGM) is an advanced technology that delivers a distinct view of genome structure. It presents numerous benefits compared to conventional sequencing techniques, as well as karyotyping in identifying large-scale structural variations (SVs). SVs refer to significant alterations in the structure of a genome that go beyond the changes of individual nucleotides. These variations can have substantial effects on gene function and are linked to various genetic diseases and disorders. There are several types of SVs, including copy number variations, such as duplications or deletions, translocations, inversions, fusions, and complex rearrangements. OGM has evolved as an innovative technology that offers high-resolution insights into genomic structures. Unlike conventional sequencing techniques such as next-generation sequencing, which concentrate on decoding short DNA segments, OGM allows for the direct visualization of long DNA strands, delivering a comprehensive, large-scale perspective of the genome’s organization. This capability makes it an effective tool for detecting SVs, which may be overlooked by other techniques. Applications of OGM are mostly in cancer genomics to detect chromosomal rearrangements and decode rare genetic disorders. OGM can also be applied in plant science, where large-scale SVs may contribute to traits such as disease. In recent years, a surge in OGM analysis has been witnessed, primarily due to the higher resolution in detecting SVs. Further, with longer reads, OGM helps in the discovery of complex and rare genomic variations.8 OGM protocol employs a paramagnetic disk designed to capture DNA during wash steps, which helps to minimize the shearing forces. Consequently, the resulting DNA fragments range from approximately 150 kilobases (kbp) to megabases (Mbp) in length, which is around 5–10 times longer than the average fragment size obtained through conventional DNA isolation techniques, making them ideal for OGM. To summarize, OGM serves as a robust technology that facilitates the direct observation of extensive SVs within the genome, offering essential insights for genomic research, clinical diagnostics, and the advancement of personalized medicine.
2
Tang, Guilin, Zhenya Tang, Rashmi Kanagal-Shamanna, et al. "Optical genome mapping for cytogenomic analysis of hematological neoplasms." Journal of Clinical Oncology 41, no. 16_suppl (2023): e19016-e19016. http://dx.doi.org/10.1200/jco.2023.41.16_suppl.e19016.
Full textAbstract:
e19016 Background: Optical genome mapping (OGM) provides a genome-wide analysis for structural variants and copy number changes in one-assay. Compared with conventional G-banded karyotyping (GBK), OGM provides significantly higher resolution and does not require metaphase cells. In this study, we assessed the added value of OGM for cytogenomic analysis of hematological neoplasms. Methods: OGM was performed on blood or bone marrow using Saphyr from Bionano Genomics on 63 patients diagnosed with various types of hematological malignancy (see Table). Variant calling was made by the Rare Variant Analysis pipeline on Bionano Access after applying recommended filters. Each patient had karyotype and/or fluorescence in situ hybridization (FISH) results available for comparison and confirmation. Only Tier 1 (pathogenic) and Tier 2 (likely pathologic) abnormalities were included for comparison purposes in this study. Results: The results were completely concordant between GBK/FISH and OGM in 30 (47.6%) patients, including 10 patients who showed no cytogenetic abnormality (normal). Fully discordant results were found in 8 (12.7%) patients: 2 had an abnormal karyotype but normal OGM, the discrepancy was mainly due to the clonal size (<20%) below the limitation of detection of OGM; 6 had a normal karyotype but cytogenetic abnormalities were detected by OGM, the discrepancy was mainly due to failure of tumor cells growth (n=5) or subtle cytogenetic abnormality undetectable by GBK (n=1). Partially concordant results between karyotype/FISH and OGM were observed in 25 (40%) patients, some abnormalities were detected by both, some were detected by GBK alone (n=4) or by OGM alone (n=25), the latter group included 10 cases with chromothripsis which only be detected by OGM. Overall, OGM provided clinically significant information in 14 (22%) patients regarding diagnosis, risk stratification, and/or identifying therapeutic targets. The added value was more common in lymphoid neoplasms (9 of 27 patients, 33%). Conclusions: OGM provides additional clinically relevant cytogenetic information in the workup of hematological neoplasms. This added value is more apparent in lymphoid neoplasms. These improvements are largely contributable to the higher resolution provided by OGM and analysis independent of metaphase cells. A major limitation of OGM usage is the need for a clonal size of at least 20%. [Table: see text]
3
Xu, Yiyun, Qinxin Zhang, Yan Wang, et al. "Optical Genome Mapping for Chromosomal Aberrations Detection—False-Negative Results and Contributing Factors." Diagnostics 14, no. 2 (2024): 165. http://dx.doi.org/10.3390/diagnostics14020165.
Full textAbstract:
Optical genome mapping (OGM) has been known as an all-in-one technology for chromosomal aberration detection. However, there are also aberrations beyond the detection range of OGM. This study aimed to report the aberrations missed by OGM and analyze the contributing factors. OGM was performed by taking both GRCh37 and GRCh38 as reference genomes. The OGM results were analyzed in blinded fashion and compared to standard assays. Quality control (QC) metrics, sample types, reference genome, effective coverage and classes and locations of aberrations were then analyzed. In total, 154 clinically reported variations from 123 samples were investigated. OGM failed to detect 10 (6.5%, 10/154) aberrations with GRCh37 assembly, including five copy number variations (CNVs), two submicroscopic balanced translocations, two pericentric inversion and one isochromosome (mosaicism). All the samples passed pre-analytical and analytical QC. With GRCh38 assembly, the false-negative rate of OGM fell to 4.5% (7/154). The breakpoints of the CNVs, balanced translocations and inversions undetected by OGM were located in segmental duplication (SD) regions or regions with no DLE-1 label. In conclusion, besides variations with centromeric breakpoints, structural variations (SVs) with breakpoints located in large repetitive sequences may also be missed by OGM. GRCh38 is recommended as the reference genome when OGM is performed. Our results highlight the necessity of fully understanding the detection range and limitation of OGM in clinical practice.
4
Soler, Gwendoline, Zangbéwendé Guy Ouedraogo, Carole Goumy, et al. "Optical Genome Mapping in Routine Cytogenetic Diagnosis of Acute Leukemia." Cancers 15, no. 7 (2023): 2131. http://dx.doi.org/10.3390/cancers15072131.
Full textAbstract:
Cytogenetic aberrations are found in 65% of adults and 75% of children with acute leukemia. Specific aberrations are used as markers for the prognostic stratification of patients. The current standard cytogenetic procedure for acute leukemias is karyotyping in combination with FISH and RT-PCR. Optical genome mapping (OGM) is a new technology providing a precise identification of chromosomal abnormalities in a single approach. In our prospective study, the results obtained using OGM and standard techniques were compared in 29 cases of acute myeloid (AML) or lymphoblastic leukemia (ALL). OGM detected 73% (53/73) of abnormalities identified by standard methods. In AML cases, two single clones and three subclones were missed by OGM, but the assignment of patients to cytogenetic risk groups was concordant in all patients. OGM identified additional abnormalities in six cases, including one cryptic structural variant of clinical interest and two subclones. In B-ALL cases, OGM correctly detected all relevant aberrations and revealed additional potentially targetable alterations. In T-ALL cases, OGM characterized a complex karyotype in one case and identified additional abnormalities in two others. In conclusion, OGM is an attractive alternative to current multiple cytogenetic testing in acute leukemia that simplifies the procedure and reduces costs.
5
Giguère, Amélie, Isabelle Raymond-Bouchard, Vanessa Collin, Jean-Sébastien Claveau, Josée Hébert, and Richard LeBlanc. "Optical Genome Mapping Reveals the Complex Genetic Landscape of Myeloma." Cancers 15, no. 19 (2023): 4687. http://dx.doi.org/10.3390/cancers15194687.
Full textAbstract:
Fluorescence in situ hybridization (FISH) on enriched CD138 plasma cells is the standard method for identification of clinically relevant genetic abnormalities in multiple myeloma. However, FISH is a targeted analysis that can be challenging due to the genetic complexity of myeloma. The aim of this study was to evaluate the potential of optical genome mapping (OGM) to detect clinically significant cytogenetic abnormalities in myeloma and to provide larger pangenomic information. OGM and FISH analyses were performed on CD138-purified cells of 20 myeloma patients. OGM successfully detected structural variants (SVs) (IGH and MYC rearrangements), copy number variants (CNVs) (17p/TP53 deletion, 1p deletion and 1q gain/amplification) and aneuploidy (gains of odd-numbered chromosomes, monosomy 13) classically expected with myeloma and led to a 30% increase in prognosis yield at our institution when compared to FISH. Despite challenges in the interpretation of OGM calls for CNV and aneuploidy losses in non-diploid genomes, OGM has the potential to replace FISH as the standard of care analysis in clinical settings and to efficiently change how we identify prognostic and predictive markers for therapies in the future. To our knowledge, this is the first study highlighting the feasibility and clinical utility of OGM in myeloma.
6
Díaz-González, Álvaro, Elvira Mora, Gayane Avetisyan, et al. "Cytogenetic Assessment and Risk Stratification in Myelofibrosis with Optical Genome Mapping." Cancers 15, no. 11 (2023): 3039. http://dx.doi.org/10.3390/cancers15113039.
Full textAbstract:
Cytogenetic assessment in myelofibrosis is essential for risk stratification and patient management. However, an informative karyotype is unavailable in a significant proportion of patients. Optical genome mapping (OGM) is a promising technique that allows for a high-resolution assessment of chromosomal aberrations (structural variants, copy number variants, and loss of heterozygosity) in a single workflow. In this study, peripheral blood samples from a series of 21 myelofibrosis patients were analyzed via OGM. We assessed the clinical impact of the application of OGM for disease risk stratification using the DIPSS-plus, GIPSS, and MIPSS70+v2 prognostic scores compared with the standard-of-care approach. OGM, in combination with NGS, allowed for risk classification in all cases, compared to only 52% when conventional techniques were used. Cases with unsuccessful karyotypes (n = 10) using conventional techniques were fully characterized using OGM. In total, 19 additional cryptic aberrations were identified in 9 out of 21 patients (43%). No alterations were found via OGM in 4/21 patients with previously normal karyotypes. OGM upgraded the risk category for three patients with available karyotypes. This is the first study using OGM in myelofibrosis. Our data support that OGM is a valuable tool that can greatly contribute to improve disease risk stratification in myelofibrosis patients.
7
Nilius-Eliliwi, Verena, Wanda M. Gerding, Roland Schroers, Huu Phuc Nguyen, and Deepak B. Vangala. "Optical Genome Mapping for Cytogenetic Diagnostics in AML." Cancers 15, no. 6 (2023): 1684. http://dx.doi.org/10.3390/cancers15061684.
Full textAbstract:
The classification and risk stratification of acute myeloid leukemia (AML) is based on reliable genetic diagnostics. A broad and expanding variety of relevant aberrations are structural variants beyond single-nucleotide variants. Optical Genome Mapping is an unbiased, genome-wide, amplification-free method for the detection of structural variants. In this review, the current knowledge of Optical Genome Mapping (OGM) with regard to diagnostics in hematological malignancies in general, and AML in specific, is summarized. Furthermore, this review focuses on the ability of OGM to expand the use of cytogenetic diagnostics in AML and perhaps even replace older techniques such as chromosomal-banding analysis, fluorescence in situ hybridization, or copy number variation microarrays. Finally, OGM is compared to amplification-based techniques and a brief outlook for future directions is given.
8
Jadhav, Sachin, Meena Naik, Nishit Ojha, et al. "Application of Optical Genome Mapping to the Risk Stratification and Treatment Optimization of Hematologic Diseases." Advances in Hematology and Oncology Research 7, no. 2 (2024): 01–10. https://doi.org/10.33140/ahor.07.02.05.
Full textAbstract:
Structural Variations (SVs) play a key role in the pathogenicity of hematological malignancies. Optical Genome Mapping (OGM) is an emerging technology that enables genome-wide detection of all classes of SVs at a high resolution and sensitivity. Identification of cryptic SVs leading to gene disruption or predicted novel gene fusions could be important drivers for cancer development and/or portend a prognostic relevance, which could be used to modify the treatment plan. A cohort of 106 consented cases that had a successful OGM analysis performed were included in the study. Demographic, clinical, laboratory and treatment data were collected. Routine diagnostic and prognostic testing were done on the peripheral blood and bone marrow aspirate as indicated. Additional samples of peripheral blood and/or bone marrow were sent for OGM testing. OGM led to a change in risk stratification in 17/66 (25.75%) of patients with hematological malignancies, the majority of these patients (15/66, 22.72%), having their risk stratification upgraded with a resulting change in treatment of 14 patients. This study highlights the ability of OGM to detect rare, cryptic and clinically relevant variants that potentially impact disease diagnosis, risk stratification and actionable treatment targets.
9
Erdem, Simge, Ayşe Gül Bayrak Tokaç, Aynur Aday, et al. "Optical Genome Mapping in Newly Diagnosed Chronic Lymphocytic Leukemia." Blood 144, Supplement 1 (2024): 6758. https://doi.org/10.1182/blood-2024-202117.
Full textAbstract:
Introduction: Chronic Lymphocytic Leukemia (CLL) is a heterogeneous neoplasm originating from B cells, accounting for approximately 30% of adult leukemias. One-third of newly diagnosed patients do not need treatment, while the remainder require treatment within a few years. Genetic abnormalities are crucial for predicting the prognosis of CLL and play an important role in determining the appropriate treatment approaches. Fluorescence in situ hybridization (FISH) is the most effective test for detecting these abnormalities. Recently, Optical Genome Mapping (OGM) has been introduced, providing a more sensitive cytogenetic approach in the diagnosis and treatment of neoplasms. Methods: This study compared FISH and OGM results of 10 newly diagnosed CLL patients in the Department of Hematology at Istanbul University Istanbul Faculty of Medicine. FISH and OGM studies were performed on peripheral blood samples. A CLL panel including del(13q), del(11q)(ATM deletion), del(17p)(P53 deletion), IGH rearrangements, del(6q)(MYB deletion), and trisomy 12 were applied in the FISH analysis. DNA isolation from the peripheral blood samples and labeling-staining experiments were performed using the SP Blood and Cell Culture DNA Isolation Kit and Direct Labeling and Staining (DLS) Kits. A labeled gDNA solution was loaded onto the Saphyr chip and scanned on the Saphyr instrument. Data were analyzed using Bionano Access software (v1.7.2). Results: The mean age of patients was 62.5±11.66 years, with 7 females and 3 males. According to the FISH results, the abnormalities detected in the patients were as follows: del(13q) (16%) in patient 1; del(13q) (93%) in patient 2; del(13q) (80%) in patient 4; trisomy 12 (65%) in patient 5; del(13q) (14%) in patient 6; biallelic del(13q) (26%) in patient 7; and del(13q) (33%) in patient 9. No abnormalities were detected in patients 3, 8, and 10. According to the OGM results, the abnormalities detected in addition to those detected by FISH were: deletion (14q) in patient 1; inversion (3) and inversion (12) in patient 2; deletion (22q) and t(9;13) in patient 4; gain (2p) and inversion (3q) in patient 5; loss of X in patient 6; inversion (13) in patient 7; and gain 1p36.21 in patient 9. In patient 3, no structural variant was detected by OGM, and no abnormality was detected by FISH. Deletion (13q), deletion (22q), t(2;10), t(10;14), and gain 10q structural variants were detected by OGM in patients 8 and 10, in whom no abnormality was detected by FISH. These findings are preliminary data for our study. Discussion: All abnormalities detected by FISH were also identified by OGM. Additionally, OGM detected del(13q) in a patient (patient 8) who was normal according to FISH. Other abnormalities detected by OGM included chromosomes not covered by the CLL FISH panel. As FISH is a target-specific method, it only provides information on the regions examined. In contrast, OGM offers comprehensive genomic information and higher sensitivity compared to conventional methods. The use of OGM in the diagnosis and treatment of heterogeneous diseases such as hematologic neoplasms will enhance the identification of new biomarkers and contribute to the development of novel diagnostic, prognostic and therapeutic approaches.
10
Xiao, Qing, Ziwei Li, and Jinzhi Lu. "Optical Genome Mapping—A Cytogenomic Tool for Prenatal Diagnostics." Research in Health Science 9, no. 4 (2024): p63. http://dx.doi.org/10.22158/rhs.v9n4p63.
Full textAbstract:
Chromosome aberration is the main cause of human inherited diseases. The routine clinical tests still rely on the standardization of cellular genetics. In recent years, Optical Genome Mapping (OGM) has been developed as a high-view method to detect large-scale structural variation of human genome. It is capable of detecting structural variations which are difficult to be detected by other methods. OGM preliminarily applied in the comprehensive identification of genomic structural variations, the visual delineation of chromosomal rearrangement patterns, and the diagnosis of some dynamic mutation diseases. This review primarily focuses on the technical attributes of OGM and its application in the field of prenatal diagnosis.
11
Díaz-González, Álvaro, Cristian García-Ruiz, Gayane Avetisyan, et al. "Enhancing Cytogenetic Diagnostics: Incorporating Optical Genome Mapping in the Laboratory Routine." Blood 142, Supplement 1 (2023): 5024. http://dx.doi.org/10.1182/blood-2023-180691.
Full textAbstract:
Key findings Introduction Optical Genome Mapping (OGM) is a is a novel high-throughput diagnostic technique that overcomes the limitations of conventional cytogenetic methods. The objective of this study was to evaluate the application of OGM in the daily workflow of the cytogenetics laboratory and compare it with standard techniques. Methods A total of 180 adult or pediatric patients referred to the Cytogenetics Laboratory at Hospital La Fe during disease onset or relapse were included. The patients had the following diagnoses: aplastic anemia (AA) n = 6, B-cell acute lymphoblastic leukemia (B-ALL) n = 39, T-cell acute lymphoblastic leukemia (T-ALL) n = 9, acute myeloid leukemia (AML) n = 51, myelofibrosis (MF) n = 36, polycythemia vera (PV) n = 3, essential thrombocythemia (ET) n = 2, multiple myeloma (MM) n = 11, and myelodysplastic syndromes (MDS) n = 22. Chromosome banding analysis (CBA) was performed on bone marrow samples, and in selected cases, fluorescence in situ hybridization (FISH) was carried out using specific probes following diagnostic recommendations. For OGM analysis, high molecular weight DNA was extracted and labeled from peripheral blood (PB, n = 62) or bone marrow (BM, n = 118) following the manufacturer's protocol (Bionano, San Diego, CA, USA). Results CBA was performed on all patients except MM, where an initial FISH panel targeting IGH rearrangement, TP53 deletion, and 1q amplification was applied. Among the CBA, 61/169 (36%) patients showed a CBA without alterations, 62/169 (37%) were abnormal and 46/169 (27%) were unsuccessful. OGM successfully detected cryptic alterations in 60% (37/61) of cases previously classified as normal with CBA. Additionally, OGM identified further alterations in 56% (35/62) of cases with abnormal CBA findings. Notably, OGM demonstrated a remarkable 93% success rate in resolving previously uninformative CBA results. AA OGM did not detect clinically significant alterations or copy neutral loss of heterozygozity (CN-LOH) on chromosome 6 in this subgroup of patients. B-ALL: OGM detected alterations in all patients with a normal or uninformative karyotype. Regarding cases with a previous abnormal CBA, OGM discovered 2 cases with masked hypodiploidy. Copy Number Alterations (CNA) affecting IKZF1, PAX5, ETV6, RB1, BTG1, EBF1, CDKN2A, CDKN2B, PAR1 region, and ERG were detected in 27/39 (69%) patients, 3 of whom harbored the IKZF1plus Moreover, several cryptic rearrangements were uncovered, such as MEF2D::BCL9, RUFY1::ETV6, PDGFRB::EBF1, and PAX5::PML. T-ALL: All patients showed an uninformative or normal CBA. However, OGM discovered rearrangements in 7/9 (78%) patients, including PICALM::MLLT10, GATA3::RUNX1, or STIL::TAL1. AML OGM enabled the detection of 4 cases with cryptic NUP98::NSD1 rearrangements and 2 cases with tandem duplication of KMT2A. Additionally, OGM successfully identified the partner involved in a previously uncharacterized KMT2A rearrangement ( KMT2A::ELL). MPN (MF, PV and ET) = The main utility of OGM was observed in MF, as it resolved all cases with uninformative CBA. MM Primary limitations in these cases were low plasma cell infiltration and difficulty in DNA extraction from total nucleated cells. Only one case showed an infiltration rate higher than 15%, as determined by flow cytometry. Consequently, 7 cases obtained a normal OGM result despite alterations detected by FISH. However, OGM successfully identified a cryptic rearrangement involving MYC and provided a detailed characterization of CNA in the remaining cases. MDS OGM resolved uninformative karyotypes in the subgroup of MDS with fibrosis. Additionally, the resolution of OGM allowed the detection of a t(3;8)(q26.2;q24.21) with a variant allele frequency of 6%, involving MECOM rearrangement, in a patient who later progressed to AML. In total, 8 cases were uninformative with OGM, mainly because of poor sample quality or low cellularity. Conclusion This study demonstrates the utility of integrating emerging technologies like OGM into the daily routine of the laboratory. DNA extraction should be performed through selected CD138 cells in multiple myeloma
12
Barford, Ruby G., Emily Whittle, Laura Weir, et al. "Use of Optical Genome Mapping to Detect Structural Variants in Neuroblastoma." Cancers 15, no. 21 (2023): 5233. http://dx.doi.org/10.3390/cancers15215233.
Full textAbstract:
Background: Neuroblastoma is the most common extracranial solid tumour in children, accounting for 15% of paediatric cancer deaths. Multiple genetic abnormalities have been identified as prognostically significant in neuroblastoma patients. Optical genome mapping (OGM) is a novel cytogenetic technique used to detect structural variants, which has not previously been tested in neuroblastoma. We used OGM to identify copy number and structural variants (SVs) in neuroblastoma which may have been missed by standard cytogenetic techniques. Methods: Five neuroblastoma cell lines (SH-SY5Y, NBLW, GI-ME-N, NB1691 and SK-N-BE2(C)) and two neuroblastoma tumours were analysed using OGM with the Bionano Saphyr® instrument. The results were analysed using Bionano Access software and compared to previous genetic analyses including G-band karyotyping, FISH (fluorescent in situ hybridisation), single-nucleotide polymorphism (SNP) array and RNA fusion panels for cell lines, and SNP arrays and whole genome sequencing (WGS) for tumours. Results: OGM detected copy number abnormalities found using previous methods and provided estimates for absolute copy numbers of amplified genes. OGM identified novel SVs, including fusion genes in two cell lines of potential clinical significance. Conclusions: OGM can reliably detect clinically significant structural and copy number variations in a single test. OGM may prove to be more time- and cost-effective than current standard cytogenetic techniques for neuroblastoma.
13
Pang, Andy W. C., Karena Kosco, Nikhil S. Sahajpal, et al. "Analytic Validation of Optical Genome Mapping in Hematological Malignancies." Biomedicines 11, no. 12 (2023): 3263. http://dx.doi.org/10.3390/biomedicines11123263.
Full textAbstract:
Structural variations (SVs) play a key role in the pathogenicity of hematological malignancies. Standard-of-care (SOC) methods such as karyotyping and fluorescence in situ hybridization (FISH), which have been employed globally for the past three decades, have significant limitations in terms of resolution and the number of recurrent aberrations that can be simultaneously assessed, respectively. Next-generation sequencing (NGS)-based technologies are now widely used to detect clinically significant sequence variants but are limited in their ability to accurately detect SVs. Optical genome mapping (OGM) is an emerging technology enabling the genome-wide detection of all classes of SVs at a significantly higher resolution than karyotyping and FISH. OGM requires neither cultured cells nor amplification of DNA, addressing the limitations of culture and amplification biases. This study reports the clinical validation of OGM as a laboratory-developed test (LDT) according to stringent regulatory (CAP/CLIA) guidelines for genome-wide SV detection in different hematological malignancies. In total, 60 cases with hematological malignancies (of various subtypes), 18 controls, and 2 cancer cell lines were used for this study. Ultra-high-molecular-weight DNA was extracted from the samples, fluorescently labeled, and run on the Bionano Saphyr system. A total of 215 datasets, Inc.luding replicates, were generated, and analyzed successfully. Sample data were then analyzed using either disease-specific or pan-cancer-specific BED files to prioritize calls that are known to be diagnostically or prognostically relevant. Sensitivity, specificity, and reproducibility were 100%, 100%, and 96%, respectively. Following the validation, 14 cases and 10 controls were run and analyzed using OGM at three outside laboratories showing reproducibility of 96.4%. OGM found more clinically relevant SVs compared to SOC testing due to its ability to detect all classes of SVs at higher resolution. The results of this validation study demonstrate the superiority of OGM over traditional SOC methods for the detection of SVs for the accurate diagnosis of various hematological malignancies.
14
Valkama, Andriana, Sandra Vorimo, Timo A. Kumpula, et al. "Optical Genome Mapping as an Alternative to FISH-Based Cytogenetic Assessment in Chronic Lymphocytic Leukemia." Cancers 15, no. 4 (2023): 1294. http://dx.doi.org/10.3390/cancers15041294.
Full textAbstract:
The fluorescence in situ hybridization (FISH) technique plays an important role in the risk stratification and clinical management of patients with chronic lymphocytic leukemia (CLL). For genome-wide analysis, FISH needs to be complemented with other cytogenetic methods, including karyotyping and/or chromosomal microarrays. However, this is often not feasible in a diagnostic setup. Optical genome mapping (OGM) is a novel technique for high-resolution genome-wide detection of structural variants (SVs), and previous studies have indicated that OGM could serve as a generic cytogenetic tool for hematological malignancies. Herein, we report the results from our study evaluating the concordance of OGM and standard-of-care FISH in 18 CLL samples. The results were fully concordant between these two techniques in the blinded comparison. Using in silico dilution series, the lowest limit of detection with OGM was determined to range between 3 and 9% variant allele fractions. Genome-wide analysis by OGM revealed additional (>1 Mb) aberrations in 78% of the samples, including both unbalanced and balanced SVs. Importantly, OGM also enabled the detection of clinically relevant complex karyotypes, undetectable by FISH, in three samples. Overall, this study demonstrates the potential of OGM as a first-tier cytogenetic test for CLL and as a powerful tool for genome-wide SV analysis.
15
Suttorp, Julia, Jonathan Lukas Lühmann, Yvonne Lisa Behrens, et al. "Optical Genome Mapping as a Diagnostic Tool in Pediatric Acute Myeloid Leukemia." Cancers 14, no. 9 (2022): 2058. http://dx.doi.org/10.3390/cancers14092058.
Full textAbstract:
Pediatric AML is characterized by numerous genetic aberrations (chromosomal translocations, deletions, insertions) impacting its classification for risk of treatment failure. Aberrations are described by classical cytogenetic procedures (karyotyping, FISH), which harbor limitations (low resolution, need for cell cultivation, cost-intensiveness, experienced staff required). Optical Genome Mapping (OGM) is an emerging chip-based DNA technique combining high resolution (~500 bp) with a relatively short turnaround time. Twenty-four pediatric patients with AML, bi-lineage leukemia, and mixed-phenotype acute leukemia were analyzed by OGM, and the results were compared with cytogenetics. Results were discrepant in 17/24 (70%) cases, including 32 previously unknown alterations called by OGM only. One newly detected deletion and two translocations were validated by primer walking, breakpoint-spanning PCR, and DNA sequencing. As an added benefit, in two cases, OGM identified a new minimal residual disease (MRD) marker. Comparing impact on risk stratification in de novo AML, 19/20 (95%) cases had concordant results while only OGM unraveled another high-risk aberration. Thus, OGM considerably expands the methodological spectrum to optimize the diagnosis of pediatric AML via the identification of new aberrations. Results will contribute to a better understanding of leukemogenesis in pediatric AML. In addition, aberrations identified by OGM may provide markers for MRD monitoring.
16
Hahn, Logan, John DeCoteau, Karen Mochoruk, et al. "Can Optical Genome Mapping Replace Bone Marrow Biopsies in Acute Myeloid Leukemia?" Blood 144, Supplement 1 (2024): 5963. https://doi.org/10.1182/blood-2024-211936.
Full textAbstract:
Background Identifying structural variants (SVs) is essential for targeted treatment and prognosis in acute myeloid leukemia (AML) patients. Current cytogenetic techniques like karyotyping and fluorescence in situ hybridization (FISH) face challenges, leading to test failure rates of over 20% (Pullarkat 2008; Grimwade 1998). Additionally, conventional cytogenetic analysis yields normal or non-specific profiles for over one third of AML patients with analyzable karyotypes (Mawad 2012). Optical genome mapping (OGM) poses a potential solution to these limitations. OGM involves the identification of SVs through analysis of ultra-high molecular weight DNA and does not require dividing cells for analysis. OGM has much higher sensitivity than karyotyping and is typically at the 5% variant allele fraction level. Given the resolution of this technique, we hypothesize that OGM results from peripheral blood (PB) and bone marrow (BM) specimens are highly concordant, thereby obviating the need for diagnostic BM biopsies in many AML patients. In the present study, we determine the concordance rate of results obtained through OGM on PB, OGM on BM and conventional cytogenetics in a small cohort of patients with AML. Methods Fourteen consecutive adult patients with AML and greater than 20% blasts in PB, BM, or both were included in the analysis. Conventional cytogenetics (karyotype and FISH) and OGM were performed on BM or PB samples. Twelve patients had OGM performed on both PB and BM specimens. Additionally, 14 BM and 8 PB samples were analyzed by next generation sequencing (NGS) using the Oncomine Myeloid Research Assay from ThermoFisher, which includes a 40-gene DNA panel and an RNA panel covering 29 fusion drivers, in order to compare findings based on European LeukemiaNet (ELN) 2022 risk categories. Results The mean age at diagnosis was 62 years (range: 20-79) The sample consisted of 8 women and 6 men. The mean percentage of PB blasts at diagnosis was 28% (range: 0.1-88), whereas the mean percentage of BM blasts was 55% (range: 20-88%). Two patients had less than 5% blasts in the PB. By using conventional cytogenetics, 11 patients were categorized as having intermediate risk, while 3 were in the adverse risk category. When comparing conventional cytogenetics and OGM performed on either BM or PB specimens, there was agreement in all 14 cases in terms of ELN risk category. In the patients (n=12) who had OGM performed on both their PB and BM samples, there were no discrepancies detected. In the 8 patients who had OGM and NGS performed on both PB and BM, there was also complete agreement in terms of ELN risk stratification. Conclusions In this ongoing study, OGM completed on BM or PB demonstrated all the same SVs detected by conventional cytogenetics. Additionally, there was total agreement between OGM results obtained on PB or BM, even in patients with low levels of circulating blasts. These results indicate that utilizing OGM could enable clinicians to perform necessary testing for AML patients through a more sensitive and less invasive method, potentially enhancing outcomes.
17
Budurlean, Laura, Diwakar Bastihalli Tukaramrao, Lijun Zhang, Sinisa Dovat, and James Broach. "Integrating Optical Genome Mapping and Whole Genome Sequencing in Somatic Structural Variant Detection." Journal of Personalized Medicine 14, no. 3 (2024): 291. http://dx.doi.org/10.3390/jpm14030291.
Full textAbstract:
Structural variants drive tumorigenesis by disrupting normal gene function through insertions, inversions, translocations, and copy number changes, including deletions and duplications. Detecting structural variants is crucial for revealing their roles in tumor development, clinical outcomes, and personalized therapy. Presently, most studies rely on short-read data from next-generation sequencing that aligns back to a reference genome to determine if and, if so, where a structural variant occurs. However, structural variant discovery by short-read sequencing is challenging, primarily because of the difficulty in mapping regions of repetitive sequences. Optical genome mapping (OGM) is a recent technology used for imaging and assembling long DNA strands to detect structural variations. To capture the structural variant landscape more thoroughly in the human genome, we developed an integrated pipeline that combines Bionano OGM and Illumina whole-genome sequencing and applied it to samples from 29 pediatric B-ALL patients. The addition of OGM allowed us to identify 511 deletions, 506 insertions, 93 duplications/gains, and 145 translocations that were otherwise missed in the short-read data. Moreover, we identified several novel gene fusions, the expression of which was confirmed by RNA sequencing. Our results highlight the benefit of integrating OGM and short-read detection methods to obtain a comprehensive analysis of genetic variation that can aid in clinical diagnosis, provide new therapeutic targets, and improve personalized medicine in cancers driven by structural variation.
18
Barseghyan, Hayk, Doris Eisenreich, Evgenia Lindt, et al. "Optical Genome Mapping as a Potential Routine Clinical Diagnostic Method." Genes 15, no. 3 (2024): 342. http://dx.doi.org/10.3390/genes15030342.
Full textAbstract:
Chromosome analysis (CA) and chromosomal microarray analysis (CMA) have been successfully used to diagnose genetic disorders. However, many conditions remain undiagnosed due to limitations in resolution (CA) and detection of only unbalanced events (CMA). Optical genome mapping (OGM) has the potential to address these limitations by capturing both structural variants (SVs) resulting in copy number changes and balanced rearrangements with high resolution. In this study, we investigated OGM’s concordance using 87 SVs previously identified by CA, CMA, or Southern blot. Overall, OGM was 98% concordant with only three discordant cases: (1) uncalled translocation with one breakpoint in a centromere; (2) uncalled duplication with breakpoints in the pseudoautosomal region 1; and (3) uncalled mosaic triplication originating from a marker chromosome. OGM provided diagnosis for three previously unsolved cases: (1) disruption of the SON gene due to a balanced reciprocal translocation; (2) disruption of the NBEA gene due to an inverted insertion; (3) disruption of the TSC2 gene due to a mosaic deletion. We show that OGM is a valid method for the detection of many types of SVs in a single assay and is highly concordant with legacy cytogenomic methods; however, it has limited SV detection capabilities in centromeric and pseudoautosomal regions.
19
Krayem, Baher, Nivin moustafa-Hawash, Avraham Frisch, Christina Srouji, and Tsila Zuckerman. "Optical Genome Mapping Reclassifies Patients with Intermediate Risk Acute Myeloid Leukemia." Blood 144, Supplement 1 (2024): 1559. https://doi.org/10.1182/blood-2024-206768.
Full textAbstract:
Introduction Acute myeloid leukemia (AML) prognosis is stratified based on cytogenetic and molecular alterations as per the European LeukemiaNet (ELN) 2022 guidelines. Conventional cytogenetic techniques, including chromosomal karyotyping and fluorescence in situ hybridization (FISH), are widely employed in the diagnostic evaluation of AML. Optical genome mapping (OGM) is an emerging genome-wide cytogenetic technology that utilizes imaging of ultra-long labeled single DNA molecules to generate high-resolution genomic assemblies, detecting both balanced and unbalanced structural variants. This study evaluates the efficacy of OGM compared to conventional cytogenetics in classifying AML patients. Methods Conventional cytogenetic testing using karyotyping and high-risk FISH probes targeting chromosomes 3 (MECOM), 5 (monosomy or loss of q arm), 7 (monosomy or loss of q arm), 11 (KMT2A break apart probe), and 17 (loss of p arm) was performed in 74 patients with AML at a large tertiary care medical center between February 2023 and April 2024. Twenty-two patients from this cohort were categorized as intermediate risk AML according to the ELN 2022. Additionally, a next-generation sequencing (NGS) mutational panel was performed for all patients to refine their risk classification by ELN 2022. Results The median age of the patients was 60 years, with a gender distribution of 9 females and 13 males. All 22 patients exhibited a normal karyotype with no abnormalities detected by the specified FISH probes. Additionally, none of the patients had NPM1 mutations, inv(16), or t(8;21). Eight patients exhibited FLT3-ITD or FLT3-TKD mutations, classifying them as intermediate risk by ELN 2022 based solely on cytogenetics. OGM identified structural abnormalities in 8 patients (36%) that reclassified their cytogenetic risk to an adverse category. Five patients had KMT2A gene alterations: four exhibited partial tandem duplications (PTD) of exons 3 through 5 (KMT2A-PTD), associated with secondary AML (Yazi et al., Nature 2022), and one had a duplication of the long arm of chromosome 11 (11q) involving the KMT2A gene. Two patients had NUP98 translocations, which, despite not being classified as adverse by ELN 2022, have been associated with high-risk disease in pediatric AML. One patient exhibited trisomy 8, undetected by conventional karyotyping, classifying this patient as having AML with myelodysplasia-related cytogenetic abnormalities. Notably, only one of these 8 patients had an FLT3-ITD mutation, and none of the other 7 FLT3-mutated patients showed adverse cytogenetics by OGM. The NGS panel for these 8 patients with OGM-detected abnormalities revealed secondary-type mutations in two patients: one patient with trisomy 8 had AXSL1 and BCOR mutations, and the patient with 11q duplication had SRSF2 mutations. The remaining 6 patients did not have mutations affecting their risk stratification. Conclusion The high resolution of OGM enhances classification, prognostic prediction, and management of intermediate risk AML. In this cohort, OGM reclassified over one-third of patients initially categorized as intermediate risk by traditional cytogenetics, to an adverse risk group. Among the 22 patients, 8 had FLT3 mutations. Importantly, 7 out of the remaining 14 patients (50%) had findings on OGM not detected by conventional cytogenetics, underscoring the critical role of OGM in cases where conventional cytogenetic or molecular drivers for AML are not apparent. Detecting novel structural variants and cryptic translocations facilitates better risk stratification in AML patients. Additionally, the NGS panel contributed to the risk stratification of two patients with OGM findings, emphasizing the role of high-resolution cytogenetics in AML risk assessment. In summary , OGM has the potential to become the new standard for prognostic classification of patients with AML .
20
Sahajpal, Nikhil Shri, Ashis K. Mondal, Ashutosh Vashisht, et al. "Optical Genome Mapping: Integrating Structural Variations for Precise Homologous Recombination Deficiency Score Calculation." Genes 14, no. 9 (2023): 1683. http://dx.doi.org/10.3390/genes14091683.
Full textAbstract:
Homologous recombination deficiency (HRD) is characterized by the inability of a cell to repair the double-stranded breaks using the homologous recombination repair (HRR) pathway. The deficiency of the HRR pathway results in defective DNA repair, leading to genomic instability and tumorigenesis. The presence of HRD has been found to make tumors sensitive to ICL-inducing platinum-based therapies and poly(adenosine diphosphate [ADP]–ribose) polymerase (PARP) inhibitors (PARPi). However, there are no standardized methods to measure and report HRD phenotypes. Herein, we compare optical genome mapping (OGM), chromosomal microarray (CMA), and a 523-gene NGS panel for HRD score calculations. This retrospective study included the analysis of 196 samples, of which 10 were gliomas, 176 were hematological malignancy samples, and 10 were controls. The 10 gliomas were evaluated with both CMA and OGM, and 30 hematological malignancy samples were evaluated with both the NGS panel and OGM. To verify the scores in a larger cohort, 135 cases were evaluated with the NGS panel and 71 cases with OGM. The HRD scores were calculated using a combination of three HRD signatures that included loss of heterozygosity (LOH), telomeric allelic imbalance (TAI), and large-scale transitions (LST). In the ten glioma cases analyzed with OGM and CMA using the same DNA (to remove any tumor percentage bias), the HRD scores (mean ± SEM) were 13.2 (±4.2) with OGM compared to 3.7 (±1.4) with CMA. In the 30 hematological malignancy cases analyzed with OGM and the 523-gene NGS panel, the HRD scores were 7.6 (±2.2) with OGM compared to 2.6 (±0.8) with the 523-gene NGS panel. OGM detected 70.8% and 66.8% of additional variants that are considered HRD signatures in gliomas and hematological malignancies, respectively. The higher sensitivity of OGM to capture HRD signature variants might enable a more accurate and precise correlation with response to PARPi and platinum-based drugs. This study reveals HRD signatures that are cryptic to current standard of care (SOC) methods used for assessing the HRD phenotype and presents OGM as an attractive alternative with higher resolution and sensitivity to accurately assess the HRD phenotype.
21
Dremsek, Paul, Thomas Schwarz, Beatrix Weil, Alina Malashka, Franco Laccone, and Jürgen Neesen. "Optical Genome Mapping in Routine Human Genetic Diagnostics—Its Advantages and Limitations." Genes 12, no. 12 (2021): 1958. http://dx.doi.org/10.3390/genes12121958.
Full textAbstract:
In recent years, optical genome mapping (OGM) has developed into a highly promising method of detecting large-scale structural variants in human genomes. It is capable of detecting structural variants considered difficult to detect by other current methods. Hence, it promises to be feasible as a first-line diagnostic tool, permitting insight into a new realm of previously unknown variants. However, due to its novelty, little experience with OGM is available to infer best practices for its application or to clarify which features cannot be detected. In this study, we used the Saphyr system (Bionano Genomics, San Diego, CA, USA), to explore its capabilities in human genetic diagnostics. To this end, we tested 14 DNA samples to confirm a total of 14 different structural or numerical chromosomal variants originally detected by other means, namely, deletions, duplications, inversions, trisomies, and a translocation. Overall, 12 variants could be confirmed; one deletion and one inversion could not. The prerequisites for detection of similar variants were explored by reviewing the OGM data of 54 samples analyzed in our laboratory. Limitations, some owing to the novelty of the method and some inherent to it, were described. Finally, we tested the successful application of OGM in routine diagnostics and described some of the challenges that merit consideration when utilizing OGM as a diagnostic tool.
22
Tang, Zhenya, Wei Wang, Gokce A. Toruner, et al. "Optical Genome Mapping for Detection of BCR::ABL1—Another Tool in Our Toolbox." Genes 15, no. 11 (2024): 1357. http://dx.doi.org/10.3390/genes15111357.
Full textAbstract:
Background: BCR::ABL1 fusion is mostly derived from a reciprocal translocation t(9;22)(q34.1;q11.2) and is rarely caused by insertion. Various methods have been used for the detection of t(9;22)/BCR::ABL1, such as G-banded chromosomal analysis, fluorescence in situ hybridization (FISH), quantitative real-time reverse transcription-polymerase chain reaction (RT-PCR) and optical genome mapping (OGM). Understanding the strengths and limitations of each method is essential for the selection of appropriate method(s) of disease diagnosis and/or during the follow-up. Methods: We compared the results of OGM, chromosomal analysis, FISH, and/or RT-PCR in 12 cases with BCR::ABL1. Results: BCR:ABL1 was detected by FISH and RT-PCR in all 12 cases. One case with ins(22;9)/BCR::ABL1 was cryptic by chromosomal analysis and nearly missed by OGM. Atypical FISH signal patterns were observed in five cases, suggesting additional chromosomal aberrations involving chromosomes 9 and/or 22. RT-PCR identified the transcript isoforms p210 and p190 in seven and five cases, respectively. Chromosomal analysis revealed additional chromosomal aberrations in seven cases. OGM identified extra cytogenomic abnormalities in 10 cases, including chromoanagenesis and IKZF1 deletion, which were only detected by OGM. Conclusions: FISH offers rapid and definitive detection of BCR::ABL1 fusion, while OGM provides a comprehensive cytogenomic analysis. In scenarios where OGM is feasible, chromosomal analysis and RT-PCR may not offer additional diagnostic value.
23
Kovanda, Anja, Luca Lovrečić, Gorazd Rudolf, et al. "Evaluation of Optical Genome Mapping in Clinical Genetic Testing of Facioscapulohumeral Muscular Dystrophy." Genes 14, no. 12 (2023): 2166. http://dx.doi.org/10.3390/genes14122166.
Full textAbstract:
Facioscapulohumeral muscular dystrophy (FSHD) is the third most common hereditary muscular dystrophy, caused by the contraction of the D4Z4 repeats on the permissive 4qA haplotype on chromosome 4, resulting in the faulty expression of the DUX4 gene. Traditional diagnostics are based on Southern blotting, a time- and effort-intensive method that can be affected by single nucleotide variants (SNV) and copy number variants (CNV), as well as by the similarity of the D4Z4 repeats located on chromosome 10. We aimed to evaluate optical genome mapping (OGM) as an alternative molecular diagnostic method for the detection of FSHD. We first performed optical genome mapping with EnFocus™ FSHD analysis using DLE-1 labeling and the Saphyr instrument in patients with inconclusive diagnostic Southern blot results, negative FSHD2 results, and clinically evident FSHD. Second, we performed OGM in parallel with the classical Southern blot analysis for our prospectively collected new FSHD cases. Finally, panel exome sequencing was performed to confirm the presence of FSHD2. In two patients with diagnostically inconclusive Southern blot results, OGM was able to identify shortened D4Z4 repeats on the permissive 4qA alleles, consistent with the clinical presentation. The results of the prospectively collected patients tested in parallel using Southern blotting and OGM showed full concordance, indicating that OGM is a useful alternative to the classical Southern blotting method for detecting FSHD1. In a patient showing clinical FSHD but no shortened D4Z4 repeats in the 4qA allele using OGM or Southern blotting, a likely pathogenic variant in SMCHD1 was detected using exome sequencing, confirming FSHD2. OGM and panel exome sequencing can be used consecutively to detect FSHD2.
24
Puiggros, Anna, Silvia Ramos-Campoy, Joanna Kamaso, et al. "Optical Genome Mapping: A Promising New Tool to Assess Genomic Complexity in Chronic Lymphocytic Leukemia (CLL)." Cancers 14, no. 14 (2022): 3376. http://dx.doi.org/10.3390/cancers14143376.
Full textAbstract:
Novel treatments in chronic lymphocytic leukemia (CLL) have generated interest regarding the clinical impact of genomic complexity, currently assessed by chromosome banding analysis (CBA) and chromosomal microarray analysis (CMA). Optical genome mapping (OGM), a novel technique based on imaging of long DNA molecules labeled at specific sites, allows the identification of multiple cytogenetic abnormalities in a single test. We aimed to determine whether OGM is a suitable alternative to cytogenomic assessment in CLL, especially focused on genomic complexity. Cytogenomic OGM aberrations from 42 patients were compared with CBA, FISH, and CMA information. Clinical–biological characteristics and time to first treatment (TTFT) were analyzed according to the complexity detected by OGM. Globally, OGM identified 90.3% of the known alterations (279/309). Discordances were mainly found in (peri-)centromeric or telomeric regions or subclonal aberrations (<15–20%). OGM underscored additional abnormalities, providing novel structural information on known aberrations in 55% of patients. Regarding genomic complexity, the number of OGM abnormalities had better accuracy in predicting TTFT than current methods (C-index: 0.696, 0.602, 0.661 by OGM, CBA, and CMA, respectively). A cut-off of ≥10 alterations defined a complex OGM group (C-OGM, n = 12), which included 11/14 patients with ≥5 abnormalities by CBA/CMA and one patient with chromothripsis (Kappa index = 0.778; p < 0.001). Moreover, C-OGM displayed enrichment of TP53 abnormalities (58.3% vs. 3.3%, p < 0.001) and a significantly shorter TTFT (median: 2 vs. 43 months, p = 0.014). OGM is a robust technology for implementation in the routine management of CLL patients, although further studies are required to define standard genomic complexity criteria.
25
Efthymiou, Stephanie, Richard J. L. F. Lemmers, Venugopalan Y. Vishnu, et al. "Optical Genome Mapping for the Molecular Diagnosis of Facioscapulohumeral Muscular Dystrophy: Advancement and Challenges." Biomolecules 13, no. 11 (2023): 1567. http://dx.doi.org/10.3390/biom13111567.
Full textAbstract:
Facioscapulohumeral muscular dystrophy (FSHD) is the second most common muscular dystrophy in adults, and it is associated with local D4Z4 chromatin relaxation, mostly via the contraction of the D4Z4 macrosatellite repeat array on chromosome 4q35. In this study, we aimed to investigate the use of Optical Genome Mapping (OGM) as a diagnostic tool for testing FSHD cases from the UK and India and to compare OGM performance with that of traditional techniques such as linear gel (LGE) and Pulsed-field gel electrophoresis (PFGE) Southern blotting (SB). A total of 6 confirmed and 19 suspected FSHD samples were processed with LGE and PFGE, respectively. The same samples were run using a Saphyr Genome-Imaging Instrument (1-color), and the data were analysed using custom EnFocus FSHD analysis. OGM was able to confirm the diagnosis of FSHD1 in all FSHD1 cases positive for SB (n = 17), and D4Z4 sizing highly correlated with PFGE-SB (p < 0.001). OGM correctly identified cases with mosaicism for the repeat array contraction (n = 2) and with a duplication of the D4Z4 repeat array. OGM is a promising new technology able to unravel structural variants in the genome and seems to be a valid tool for diagnosing FSHD1.
26
Liu, Ming, Yang Zhang, Xue Chen, et al. "Deciphering the Structural Variants in B Cell Acute Lymphoblastic Leukemia By Optical Genome Mapping." Blood 142, Supplement 1 (2023): 1610. http://dx.doi.org/10.1182/blood-2023-189032.
Full textAbstract:
Introduction Structural variants (SVs) of the genome play a key role in the leukemogenesis and development of B cell lymphoblastic leukemia (B-ALL), including gene deletion, amplification, translocation, and other forms. Methods for analyzing SVs and CNVs include karyotype analysis, fluorescence in situ hybridization, gene chips, and high-throughput gene sequencing technologies. Optical genome mapping (OGM) is a novel ultra-long single-molecule DNA detection based high throughput SVs analysis technology, which has the characteristics of whole genome coverage, high detection incidence and sensitivity. There were few publications presenting technical concordance of SVs detection beween karyotyping and OGM, and there are no systematic studies comparing the concordance of OGM and RNA-seq in detecting gene fusion. This study aimed to compare the concordance of OGM and RNA-seq in the detection of fusion genes in B-ALL cases, and the additional findings using OGM technology. Methods Bone marrow aspirates of 70 patients with newly diagnosed or relapsed/refractory B-ALL were recruited into the study. All samples were conducted with both OGM and transcriptome sequencing (RNA-seq). Among these cases, 42 males and 28 females, 30 pediatric (&lt; 18 years) and 40 adults (≥ 18 years) cases, ages ranged 4-60 years (median 16 years). Results Totally 50 gene fusions were reported in 48 cases, with 2 cases each carrying two fusion genes ( BCR::ABL1/ PAX5::ELK3 and P2RY8::CRLF2/ PAX5::GSE1, respectively) (Figure 1A). OGM and RNA-seq have complete concordance in reporting gene fusions, and OGM provides further insight into the genomic events that lead to gene fusion. A subtype of B-ALL characterized by UBTF microdeletion leading to UBTF::ATXN7L3 fusion and PAN3 downstream deletion-induced CDX2 aberrant expression has been reported recently, and has been accepted by the International Consensus Classification as a novel molecular subtype of UBTF/CDX2 of B-ALL. We performed the OGM investigation on 6 UBTF/CDX2 cases which were identified by RNA-seq. OGM identified both microdeletion events in all 6 cases, and further reported 1q amplification in 3 of them (Figure 1B, C). B-lymphocyte differentiation-associated transcription factor gene defects are common and important genetic abnormalities in B-ALL, often manifested as complete or partial deletion of genes. We focused on a panel including 30 genes in the OGM data and determined IKZF1 deletion in 35 patients, CDKN2A/B deletion in 32 patients, and PAX5 deletion in 25 patients (Figure 1 A). Follow-up data showed that patients with CDKN2A/B deletion had a worse prognosis than those without CDKN2A/B deletion ( P = 0.025). Conclusion This is the first B-ALL cohort to systematically compare OGM and RNA-seq in gene fusion detection, and the result showed complete consistency. RNA-seq has significant advantages in analyzing gene fusion transcripts, while OGM has technical advantages in analyzing SVs at the genome level. Combining the two technologies can accurately analyze gene fusion and other SVs in B-ALL, significantly improve the detection rate of SVs with important pathological/diagnostic classification significance, and may bring new discoveries on SVs and pathogenic mechanisms.
27
Tembrink, Marco, Wanda Maria Gerding, Stefan Wieczorek, et al. "Novel NUP98::ASH1L Gene Fusion in Acute Myeloid Leukemia Detected by Optical Genome Mapping." Cancers 15, no. 11 (2023): 2942. http://dx.doi.org/10.3390/cancers15112942.
Full textAbstract:
Optical genome mapping (OGM) recently has demonstrated the potential to improve genetic diagnostics in acute myeloid leukemia (AML). In this study, OGM was utilized as a tool for the detection of genome-wide structural variants and disease monitoring. A previously unrecognized NUP98::ASH1L fusion was detected in an adult patient with secondary AML. OGM identified the fusion of NUP98 to Absent, Small, or Homeotic-Like Histone Lysine Methyltransferase (ASH1L) as result of a complex structural rearrangement between chromosomes 1 and 11. A pipeline for the measurement of rare structural variants (Rare Variant Pipeline, Bionano Genomics, San Diego, USA) was used for detection. As NUP98 and other fusions are relevant for disease classification, this demonstrates the necessity for methods such as OGM for cytogenetic diagnostics in AML. Furthermore, other structural variants showed discordant variant allele frequencies at different time points over the course of the disease and treatment pressure, indicating clonal evolution. These results support OGM to be a valuable tool for primary diagnostics in AML as well as longitudinal testing for disease monitoring and deepening our understanding of genetically heterogenous diseases.
28
Liu, Ming, Yang Zhang, Xue Chen, et al. "Deciphering the Structural Variants in Acute Myeloid Leukemia and Myelodysplastic Neoplasms By Optical Genome Mapping." Blood 142, Supplement 1 (2023): 6018. http://dx.doi.org/10.1182/blood-2023-189366.
Full textAbstract:
Introduction Acute myeloid leukemia (AML) and myelodysplastic neoplasm (MDS) are common hematological malignancies, and the majority of patients carry genetic mutations, structural variants (SVs) and copy number variants (CNVs). Identifying these variants is important for diagnosis and prognosis, and in some cases can alter treatment management and outcomes. Methods for analyzing SVs and CNVs include karyotype analysis, fluorescence in situ hybridization, gene chips, and high-throughput gene sequencing technologies. Optical genome mapping (OGM) is a novel ultra-long single-molecule DNA detection based high throughput SVs analysis technology, which has the characteristics of whole genome coverage, high detection incidence and sensitivity. There were few publications presenting technical concordance of SVs detection between karyotyping and OGM, and there are no systematic studies comparing the concordance of OGM versus transcriptome sequencing (RNA-seq) in detecting gene fusion. This study aimed to compare the concordance of OGM and RNA-seq in the detection of fusion genes in AML and MDS cases, and the additional findings using OGM technology. Methods Bone marrow aspirates of 52 newly diagnosed or relapsed/refractory AML/MDS patients were recruited for OGM, RNA-seq, and leukemia-related gene DNA panel sequencing. Among these cases, 36 males and 16 were females, 15 pediatric (&lt; 18 years) and 37 adults (≥18 years), with a median age of 31 years. Results Based on the RNA-seq results, 29/52 (55.8%) cases were detected with pathogenic gene fusions, including RUNX1::RUNX1T1, CBFB::MYH11, KMT2Aretc. (Figure 1). All those fusions were detected by OGM. For SVs with VAF&gt;5%, the concordance was 98.1% (51/52 cases) when comparing OGM with karyotyping. OGM missed one case whose translocation happened close to the centromere. OGM reported more pathological variants with clinically significant in 5/52 cases (9.62%) and helped revise karyotype results in 1 case with clarifying marker chromosome. According to the ELN-2022 risk stratification mainly based on karyotype results, OGM's report results helped revise the risk stratification of 3 patients from intermediate to high risk. Fifty of 52 (96.2%) patients carried the gene mutation detected by the gene sequencing panel (Figure 1). In the samples of 4 patients who relapsed after receiving allogeneic hematopoietic stem cell transplantation (allo-HSCT) with donors and patients of different genders, we can infer the proportion of male and female DNA based on the copy number of chr Y detected by OGM, and then determine the proportion of donor cells. Conclusion This is the first AML cohort study to systematically compare the performance of OGM and RNA-seq, and the reported results of fusion genes are completely consistent. This is also the first report of applying the OGM technology in patients who relapsed after allo-HSCT and for chimerism analysis. Combined using OGM and targeted sequencing to fully characterize the CNV, SV, and mutation can be used for accurate stratification risk of AML/MDS. In conclusion, combining OGM and NGS can significantly improve the detection rate of genetic abnormalities with important pathological/diagnostic significance, and may bring new discoveries on SVs and pathogenic mechanisms.
29
Vieler, Lisa-Marie, Verena Nilius-Eliliwi, Roland Schroers, Deepak Ben Vangala, Huu Phuc Nguyen, and Wanda Maria Gerding. "Optical Genome Mapping Reveals and Characterizes Recurrent Aberrations and New Fusion Genes in Adult ALL." Genes 14, no. 3 (2023): 686. http://dx.doi.org/10.3390/genes14030686.
Full textAbstract:
(1) Background: In acute lymphoblastic leukemia (ALL) the genetic characterization remains challenging. Due to the genetic heterogeneity of mutations in adult patients, only a small proportion of aberrations can be analyzed with standard routine diagnostics. Optical genome mapping (OGM) has recently opened up new possibilities for the characterization of structural variants on a genome-wide level, thus enabling simultaneous analysis for a broad spectrum of genetic aberrations. (2) Methods: 11 adult ALL patients were examined using OGM. (3) Results: Genetic results obtained by karyotyping and FISH were confirmed by OGM for all patients. Karyotype was redefined, and additional genetic information was obtained in 82% (9/11) of samples by OGM, previously not diagnosed by standard of care. Besides gross-structural chromosome rearrangements, e.g., ring chromosome 9 and putative isodicentric chromosome 8q, deletions in CDKN2A/2B were detected in 7/11 patients, defining an approx. 20 kb minimum region of overlap, including an alternative exon 1 of the CDKN2A gene. The results further confirm recurrent ALL aberrations (e.g., PAX5, ETV6, VPREB1, IKZF1). (4) Conclusions: Genome-wide OGM analysis enables a broad genetic characterization in adult ALL patients in one single workup compared to standard clinical testing, facilitating a detailed genetic diagnosis, risk-stratification, and target-directed treatment strategies.
30
Coccaro, Nicoletta, Luisa Anelli, Antonella Zagaria, et al. "Feasibility of Optical Genome Mapping in Cytogenetic Diagnostics of Hematological Neoplasms: A New Way to Look at DNA." Diagnostics 13, no. 11 (2023): 1841. http://dx.doi.org/10.3390/diagnostics13111841.
Full textAbstract:
Optical genome mapping (OGM) is a new genome-wide technology that can reveal both structural genomic variations (SVs) and copy number variations (CNVs) in a single assay. OGM was initially employed to perform genome assembly and genome research, but it is now more widely used to study chromosome aberrations in genetic disorders and in human cancer. One of the most useful OGM applications is in hematological malignancies, where chromosomal rearrangements are frequent and conventional cytogenetic analysis alone is insufficient, necessitating further confirmation using ancillary techniques such as fluorescence in situ hybridization, chromosomal microarrays, or multiple ligation-dependent probe amplification. The first studies tested OGM efficiency and sensitivity for SV and CNV detection, comparing heterogeneous groups of lymphoid and myeloid hematological sample data with those obtained using standard cytogenetic diagnostic tests. Most of the work based on this innovative technology was focused on myelodysplastic syndromes (MDSs), acute myeloid leukemia (AML), and acute lymphoblastic leukemia (ALL), whereas little attention was paid to chronic lymphocytic leukemia (CLL) or multiple myeloma (MM), and none was paid to lymphomas. The studies showed that OGM can now be considered as a highly reliable method, concordant with standard cytogenetic techniques but able to detect novel clinically significant SVs, thus allowing better patient classification, prognostic stratification, and therapeutic choices in hematological malignancies.
31
Goumy, Carole, Zangbéwendé Guy Ouedraogo, Elodie Bellemonte, et al. "Feasibility of Optical Genome Mapping from Placental and Umbilical Cord Sampled after Spontaneous or Therapeutic Pregnancy Termination." Diagnostics 13, no. 23 (2023): 3576. http://dx.doi.org/10.3390/diagnostics13233576.
Full textAbstract:
Optical genome mapping (OGM) is an alternative to classical cytogenetic techniques to improve the detection rate of clinically significant genomic abnormalities. The isolation of high-molecular-weight (HMW) DNA is critical for a successful OGM analysis. HMW DNA quality depends on tissue type, sample size, and storage conditions. We assessed the feasibility of OGM analysis of DNA from nine umbilical cord (UC) and six chorionic villus (CV) samples collected after the spontaneous or therapeutic termination of pregnancy. We analyzed quality control metrics provided by the Saphyr system (Bionano Genomics) and assessed the length of extracted DNA molecules using pulsed-field capillary electrophoresis. OMG data were successfully analyzed for all six CV samples. Five of the UC samples did not meet the Saphyr quality criteria, mainly due to poor DNA quality. In this regard, we found that DNA quality assessment with pulsed-field capillary electrophoresis can predict a successful OGM analysis. OGM data were fully concordant with the results of standard cytogenetic methods. Moreover, OGM detected an average of 14 additional structural variants involving OMIM genes per sample. On the basis of our results, we established the optimal conditions for sample storage and preparation required for a successful OGM analysis. We recommend checking DNA quality before analysis with pulsed-field capillary electrophoresis if the storage conditions were not ideal or if the quality of the sample is poor. OGM can therefore be performed on fetal tissue harvested after the termination of pregnancy, which opens up the perspective for improved diagnostic yield.
32
Ye, J. Christine, Guilin Tang, Oren Pasvolsky, et al. "Unveiling Clinical Potential: Exploring Cytogenomic Aberrations through Optical Genomic Mapping in Multiple Myeloma." Blood 144, Supplement 1 (2024): 1971. https://doi.org/10.1182/blood-2024-212346.
Full textAbstract:
Introduction: Optical genome mapping (OGM) is a novel DNA-based technology for comprehensive genome-wide analysis of cytogenomic abnormalities. Multiple Myeloma (MM) is characterized by recurrent cytogenetic abnormalities including copy number variants (CNVs) such as hyperdiploidy, gain of 1q, loss of 1p, del(17p), del(13q); as well as structural variants (SVs) such as chromosomal rearrangements involving IgH. This study assessed the use of OGM compared to fluorescence in situ hybridization (FISH) and karyotyping in clinical MM cases. Methods: Bone marrow aspirate (BMA) samples with &gt;20% plasma cells from MM patients (pts) at a single institute (March 2023 - April 2024) were collected, and subjected to OGM, karyotyping, and FISH analysis for rearrangements of IGH/CCND1, IGH/FGFR3, IGH/MAF, MYC, and numerical changes of CDKN2C/CKS1B, CDKN2A/CEP9, RB1/13q34, and TP53/CEP17. Cytogenomic findings detected by OGM were classified as pathogenic/likely pathogenic, or uncertain clinical significance. Clinical data including staging, extramedullary disease and Line of therapy (LOT) were also collected. Results: The study cohort included newly diagnosed MM (NDMM, n=10) and relapsed refractory MM (RRMM, n=15). OGM detected all cytogenomic aberrations which were reported by karyotyping and FISH. Furthermore, OGM identified additional cytogenomic abnormalities in 15 (60%) of patients that were not identified by FISH and karyotyping. OGM identified 3 or more CNVs in 7 pts and SVs in 8 pts, and uncharacterized cytogenetic aberrations in 15 patients. Notably del(17p) was detected in 2 pts by FISH but not by OGM, likely due to the small clonal size below OGM's detection limit (20%). MYC rearrangement (eg MYC::IGH) was detected by both FISH and OGM, however with OGM identifying additional MYC partner genes (IGL, PECAM1, NBEA and TENT5C). Furthermore several abnormalities involving novel genes were exclusively detected by OGM only: PTK2, PVT1, and ARIH2. Chromoanagenesis was detected only by OGM in 6 pts (n=1 for NDMM; n=5 for RRMM). The NDMM pt with chromoanagenesis achieved only a partial response after induction therapy. RRMM pts with chromoanagenesis demonstrated functionally aggressive clinical features, all required intensive chemotherapy regimens such as hypercytoxan, hyperCVAD, and also novel bispecific antibodies. Chromoanagenesis can present either independently or in combination with known high-risk FISH features. Conclusion: OGM, as a novel cytogenomic technique, offers broader genomic coverage compared to current FISH probe sets (with limited targets) and much higher genomic resolution and sensitivity compared to karyotyping. OGM may complement classical cytogenetics for the diagnosis and risk stratification in MM. OGM's ability to detect chromoanagenesis is promising, despite its current limitation in detection sensitivity which could be improved by cell sorting techniques. Chromoanagenesis identified by OGM can potentially serve as a biomarker for complex chromosomal rearrangement and genomic instability, and also for strategizing the subsequent LOTs for more favorable clinical responses. Future prospective studies are warranted.
33
Facchini, Stefano, Natalia Dominik, Arianna Manini, et al. "Optical Genome Mapping Enables Detection and Accurate Sizing of RFC1 Repeat Expansions." Biomolecules 13, no. 10 (2023): 1546. http://dx.doi.org/10.3390/biom13101546.
Full textAbstract:
A recessive Short Tandem Repeat expansion in RFC1 has been found to be associated with cerebellar ataxia, neuropathy and vestibular areflexia syndrome (CANVAS), and to be a frequent cause of late onset ataxia and sensory neuropathy. The usual procedure for sizing these expansions is based on Southern Blotting (SB), a time-consuming and a relatively imprecise technique. In this paper, we compare SB with Optical Genome Mapping (OGM), a method for detecting Structural Variants (SVs) based on the measurement of distances between fluorescently labelled probes, for the diagnosis of RFC1 CANVAS and disease spectrum. The two methods are applied to 17 CANVAS patients’ blood samples and resulting sizes compared, showing a good agreement. Further, long-read sequencing is used for two patients to investigate the agreement of sizes with either SB or OGM. Our study concludes that OGM represents a viable alternative to SB, allowing for a simpler technique, a more precise sizing of the expansion and ability to expand analysis of SV in the entire genome as opposed to SB which is a locus specific method.
34
Gao, Huixia, Hanli Xu, Chanjuan Wang, et al. "Optical Genome Mapping for Comprehensive Assessment of Chromosomal Aberrations and Discovery of New Fusion Genes in Pediatric B-Acute Lymphoblastic Leukemia." Cancers 15, no. 1 (2022): 35. http://dx.doi.org/10.3390/cancers15010035.
Full textAbstract:
Purpose: To assess the potential added value of Optical Genomic Mapping (OGM) for identifying chromosomal aberrations. Methods: We utilized Optical Genomic Mapping (OGM) to determine chromosomal aberrations in 46 children with B-cell Acute lymphoblastic leukemia ALL (B-ALL) and compared the results of OGM with conventional technologies. Partial detection results were verified by WGS and PCR. Results: OGM showed a good concordance with conventional cytogenetic techniques in identifying the reproducible and pathologically significant genomic SVs. Two new fusion genes (LMNB1::PPP2R2B and TMEM272::KDM4B) were identified by OGM and verified by WGS and RT-PCR for the first time. OGM has a greater ability to detect complex chromosomal aberrations, refine complicated karyotypes, and identify more SVs. Several novel fusion genes and single-gene alterations, associated with definite or potential pathologic significance that had not been detected by traditional methods, were also identified. Conclusion: OGM addresses some of the limitations associated with conventional cytogenomic testing. This all-in-one process allows the detection of most major genomic risk markers in one test, which may have important meanings for the development of leukemia pathogenesis and targeted drugs.
35
Kovanda, A., O. Miljanović, L. Lovrečić, A. Maver, A. Hodžić, and B. Peterlin. "Value of Optical Genome Mapping (OGM) for Diagnostics of Rare Diseases: A Family Case Report." Balkan Journal of Medical Genetics 27, no. 2 (2024): 87–93. https://doi.org/10.2478/bjmg-2024-0021.
Full textAbstract:
ABSTRACT Optical genome mapping (OGM) is a novel method enabling the detection of structural genomic variants. The method is based on the laser image acquisition of single, labeled, high-molecular-weight DNA molecules and can detect structural genomic variants such as translocations, inversions, insertions, deletions, duplications, and complex structural rearrangements. We aim to present our experience with OGM at the Clinical Institute of Genomic Medicine, University Medical Centre Ljubljana, Slovenia. Since its introduction in 2021, we have used OGM for the testing of facioscapulohumeral muscular dystrophy 1, characterization and resolution of variants identified by other technologies such as microarrays, exome and genome next-generation sequencing, karyotyping, as well as testing of rare disease patients in whom no genetic cause could be identified using these methods. We present an example family case of two previously undiagnosed male siblings with an overlapping clinical presentation of thrombocytopenia, obesity, and presacral teratoma. After karyotyping, microarray analysis and next-generation sequencing, by using OGM, a maternally inherited cryptic translocation t(X;18)(q27.1;q12.2) was identified in both brothers. Despite an extended segregation analysis, based on strictly applied ACMG criteria and ClinGen guidelines, the identified translocation remains a variant of unknown significance. Despite the remaining limitations of OGM, which will hopefully be resolved by improvements in databases of known benign SV variation and the establishment of official guidelines on the clinical interpretation of OGM variants, our work highlights the complexity of the diagnostic journey, including this novel method, in rare disease cases.
36
Wang, Jiachi, Andy Pang, Karl Hong, Jill Lai, Dipa Roychoudhury, and Joyce L. Murata-Colllins. "Integrative structural variant and breakpoint detection using optical genome mapping in a patient with a transformed diffuse large B-cell lymphoma from chronic lymphocytic leukemia." Journal of Clinical Oncology 39, no. 15_suppl (2021): e19511-e19511. http://dx.doi.org/10.1200/jco.2021.39.15_suppl.e19511.
Full textAbstract:
e19511 Background: The finding of complex karyotypes has been a clinically significant finding in cancers of advanced stage or during cancer progression. Conventional cytogenetic and FISH analyses have been limited by the low-resolution of chromosomes and the number of FISH probes which can be implemented in one assay. Recent study revealed the potential of using optical genome mapping to decipher the architecture of cancer genome at nucleotide level. Methods: Karyotyping, FISH and optical genome mapping of bone marrow specimen. Results: We reported on a 63-year-old female with chronic lymphocytic leukemia for nine years and transformed to diffuse large B-cell lymphoma (DLBCL). The karyotype revealed a hypodiploid chromosomal complement: 42,X,-X,der(2)t(2;?;8)(p25;?;q11.2),t(2;9)(q3?5;p2?2),der(4)t(4;?;8)(p16;?;q11.2)t(4;15)(q35;q15),-8,-15,dic(17;21)(p11.2;p11.2),der(18)t(8;18)(q21.2;p11.32)[12]/46,XX[8]. FISH analysis showed loss of TP53, monosomy 8 with 3-5 copies of the Myc genes. Optical genome mapping analysis revealed 12 insertions, 29 deletions, 8 duplications, 6 intrachromosomal translocations and 12 interchromosomal translocations. Whole genome analysis identified multiple gains of 2p, 8p and 8q, losses of 9p, 15q and 17p. The breakpoints of two unbalanced translocation and one complex chromosomal rearrangement have been narrowed down to nucleotide resolution: ogm[GRCh37] t(2;9)(q34;p21.2) g.[chr2:211,281,003::chr9:26,532,620], ogm t(2;8)(p25.3;p23.3) g.[chr2:15,924::chr8:215,177] and ogm der(4)t(8q24.3→8q21.13→2p24.2→2q34→4p15.2→4q34.3→15q15.1) g.[chr8:80,461,191::chr2:18,079,530→chr2:211,274,379::chr4:26,381,729→chr4:180,989,408::chr15:42,404,514]. Conclusions: Integrative analysis using conventional cytogenetic and molecular cytogenomic methodologies unveil the complex architectural alterations of caner genome. The resolution achieved by optical genome mapping would potentially lead to discovery of carcinogenic mechanisms, new fusion genes, prognostic and therapeutic markers.
37
Büki, Gergely, Anna Bekő, Csaba Bödör, et al. "Identification of an NF1 Microdeletion with Optical Genome Mapping." International Journal of Molecular Sciences 24, no. 17 (2023): 13580. http://dx.doi.org/10.3390/ijms241713580.
Full textAbstract:
Neurofibromatosis type 1 (NF1) is a clinically heterogeneous neurocutaneous disorder inherited in autosomal dominant manner. Approximately 5–10% of the cases are caused by NF1 microdeletions involving the NF1 gene and its flanking regions. Microdeletions, which lead to more severe clinical manifestations, can be subclassified into four different types (type 1, 2, 3 and atypical) according to their size, the genomic location of the breakpoints and the number of genes included within the deletion. Besides the prominent hallmarks of NF1, patients with NF1 microdeletions frequently exhibit specific additional clinical manifestations like dysmorphic facial features, macrocephaly, overgrowth, global developmental delay, cognitive disability and an increased risk of malignancies. It is important to identify the genes co-deleted with NF1, because they are likely to have an effect on the clinical manifestation. Multiplex ligation-dependent probe amplification (MLPA) and microarray analysis are the primary techniques for the investigation of NF1 microdeletions. However, based on previous research, optical genome mapping (OGM) could also serve as an alternative method to identify copy number variations (CNVs). Here, we present a case with NF1 microdeletion identified by means of OGM and demonstrate that this novel technology is a suitable tool for the identification and classification of the NF1 microdeletions.
38
Singh, Harmanpreet, Nikhil S. Sahajpal, Ashis K. Mondal, et al. "Clinical Utility of Optical Genome Mapping for Improved Cytogenomic Analysis of Gliomas." Biomedicines 12, no. 8 (2024): 1659. http://dx.doi.org/10.3390/biomedicines12081659.
Full textAbstract:
A glioma is a solid brain tumor which originates in the brain or brain stem area. The diagnosis of gliomas based on standard-of-care (SOC) techniques includes karyotyping, fluorescence in situ hybridization (FISH), and chromosomal microarray (CMA), for detecting the pathogenic variants and chromosomal abnormalities. But these techniques do not reveal the complete picture of genetic complexity, thus requiring an alternative technology for better characterization of these tumors. The present study aimed to evaluate the clinical performance and feasibility of using optical genome mapping (OGM) for chromosomal characterization of gliomas. Herein, we evaluated 10 cases of gliomas that were previously characterized by CMA. OGM analysis showed concordance with the results of CMA in identifying the characterized Structural Variants (SVs) in these cases. More notably, it also revealed additional clinically relevant aberrations, demonstrating a higher resolution and sensitivity. These clinically relevant SVs included cryptic translocation, and SVs which are beyond the detection capabilities of CMA. Our analysis highlights the unique capability of OGM to detect all classes of SVs within a single assay, thereby unveiling clinically significant data with a shorter turnaround time. Adopting this diagnostic tool as a standard of care for solid tumors like gliomas shows potential for improving therapeutic management, potentially leading to more personalized and timely interventions for patients.
39
Ballesta-Alcaraz, Lucía, Mónica Bernal, Jose Ramón Vilchez, et al. "Application of Optical Genome Mapping for the Diagnosis and Risk Stratification of Myeloid and Lymphoid Malignancies." International Journal of Molecular Sciences 26, no. 12 (2025): 5763. https://doi.org/10.3390/ijms26125763.
Full textAbstract:
Optical genome mapping (OGM) is a novel, high-resolution technology for genome-wide detection of structural variants, offering clear advantages over conventional cytogenetics in hematologic malignancies. We applied OGM to a large cohort of patients with acute myeloid leukemia (AML), myelodysplastic syndromes (MDSs), and B-cell acute lymphoblastic leukemia (B-ALL) to evaluate its clinical utility. In AML and MDS, it revealed high-risk alterations such as deletions in 5q31–5q32 and 7q22, and cryptic fusions like NUP98::NSD1 that were missed by karyotyping or FISH. It also identified chromoanagenesis, a catastrophic chromosomal event linked to poor prognosis and often undetectable by standard methods. In B-ALL, OGM uncovered clinically relevant deletions in CDKN2A/B, PAX5, and IKZF1, as well as high-risk ploidy changes like hypodiploidy and hyperdiploidy, all important for risk assessment and frequently underdetected. OGM not only refines diagnosis and improves risk stratification but can also uncover cryptic and complex genomic abnormalities. Our findings support its integration into routine diagnostics to enhance classification, guide treatment decisions, and improve patient outcomes.
40
Coccaro, Nicoletta, Antonella Zagaria, Luisa Anelli, et al. "Optical Genome Mapping as a Tool to Unveil New Molecular Findings in Hematological Patients with Complex Chromosomal Rearrangements." Genes 14, no. 12 (2023): 2180. http://dx.doi.org/10.3390/genes14122180.
Full textAbstract:
Standard cytogenetic techniques (chromosomal banding analysis—CBA, and fluorescence in situ hybridization—FISH) show limits in characterizing complex chromosomal rearrangements and structural variants arising from two or more chromosomal breaks. In this study, we applied optical genome mapping (OGM) to fully characterize two cases of complex chromosomal rearrangements at high resolution. In case 1, an acute myeloid leukemia (AML) patient showing chromothripsis, OGM analysis was fully concordant with classic cytogenetic techniques and helped to better refine chromosomal breakpoints. The OGM results of case 2, a patient with non-Hodgkin lymphoma, were only partially in agreement with previous cytogenetic analyses and helped to better define clonal heterogeneity, overcoming the bias related to clonal selection due to cell culture of cytogenetic techniques. In both cases, OGM analysis led to the identification of molecular markers, helping to define the pathogenesis, classification, and prognosis of the analyzed patients. Despite extensive efforts to study hematologic diseases, standard cytogenetic methods display unsurmountable limits, while OGM is a tool that has the power to overcome these limitations and provide a cytogenetic analysis at higher resolution. As OGM also shows limits in defining regions of a repetitive nature, combining OGM with CBA to obtain a complete cytogenetic characterization would be desirable.
41
Toruner, Gokce A., Shimin Hu, Sanam Loghavi, et al. "Clinical Utility of Optical Genome Mapping as an Additional Tool in a Standard Cytogenetic Workup in Hematological Malignancies." Cancers 17, no. 9 (2025): 1436. https://doi.org/10.3390/cancers17091436.
Full textAbstract:
Background and Objective: The primary objective of this study is to evaluate the added value of optical genome mapping (OGM) when integrated into the standard cytogenetic workup (SCGW) for hematological malignancies. Methods: The study cohort comprised 519 cases with different types of hematological malignancies. OGM and SCGW (including G-banded karyotyping and fluorescence in situ hybridization) were performed on blood and/or bone marrow. The analytical sensitivity of OGM, defined as the detection of all additional cytogenomic aberrations, and its clinical utility, referring to aberrations with diagnostic, prognostic, or therapeutic significance, were assessed. Results: OGM led to increased analytical sensitivity and clinical utility in 58% and 15% of the cases, respectively. The clinical utility varied across different malignancies, with the highest utility in T-lymphoblast leukemia (52%), followed by mixed phenotype acute leukemia (43%), B-lymphoblastic leukemia (37%), other B-cell lymphomas (22%), mature T-cell leukemia/lymphoma (20%), chronic lymphocytic leukemia (14%), acute myeloid leukemia (13%), multiple myeloma (13%), mantle cell lymphoma (8%), myelodysplastic/myeloproliferative neoplasms (6%), myelodysplastic syndrome (5%), and myeloproliferative neoplasms (0%). Conclusion: Compared to SCGW, OGM detects additional cytogenomic aberrations in approximately 58% of cases. OGM provides clinical utility at varying rates across different types of hematological malignancies. Given these differences, strategic triaging can help maximize the clinical value of OGM by focusing on diseases where it offers the most significant benefit.
42
Lühmann, Jonathan Lukas, Marie Stelter, Marie Wolter, et al. "The Clinical Utility of Optical Genome Mapping for the Assessment of Genomic Aberrations in Acute Lymphoblastic Leukemia." Cancers 13, no. 17 (2021): 4388. http://dx.doi.org/10.3390/cancers13174388.
Full textAbstract:
Acute lymphoblastic leukemia (ALL) is the most prevalent type of cancer occurring in children. ALL is characterized by structural and numeric genomic aberrations that strongly correlate with prognosis and clinical outcome. Usually, a combination of cyto- and molecular genetic methods (karyotyping, array-CGH, FISH, RT-PCR, RNA-Seq) is needed to identify all aberrations relevant for risk stratification. We investigated the feasibility of optical genome mapping (OGM), a DNA-based method, to detect these aberrations in an all-in-one approach. As proof of principle, twelve pediatric ALL samples were analyzed by OGM, and results were validated by comparing OGM data to results obtained from routine diagnostics. All genomic aberrations including translocations (e.g., dic(9;12)), aneuploidies (e.g., high hyperdiploidy) and copy number variations (e.g., IKZF1, PAX5) known from other techniques were also detected by OGM. Moreover, OGM was superior to well-established techniques for resolution of the more complex structure of a translocation t(12;21) and had a higher sensitivity for detection of copy number alterations. Importantly, a new and unknown gene fusion of JAK2 and NPAT due to a translocation t(9;11) was detected. We demonstrate the feasibility of OGM to detect well-established as well as new putative prognostic markers in an all-in-one approach in ALL. We hope that these limited results will be confirmed with testing of more samples in the future.
43
Iriondo, June, Ana Gómez, Josune Zubicaray, et al. "Optical Genome Mapping as a New Tool to Overcome Conventional Cytogenetics Limitations in Patients with Bone Marrow Failure." Genes 15, no. 5 (2024): 559. http://dx.doi.org/10.3390/genes15050559.
Full textAbstract:
Cytogenetic studies are essential in the diagnosis and follow up of patients with bone marrow failure syndromes (BMFSs), but obtaining good quality results is often challenging due to hypocellularity. Optical Genome Mapping (OGM), a novel technology capable of detecting most types chromosomal structural variants (SVs) at high resolution, is being increasingly used in many settings, including hematologic malignancies. Herein, we compared conventional cytogenetic techniques to OGM in 20 patients with diverse BMFSs. Twenty metaphases for the karyotype were only obtained in three subjects (15%), and no SVs were found in any of the samples. One patient with culture failure showed a gain in chromosome 1q by fluorescence in situ hybridization, which was confirmed by OGM. In contrast, OGM provided good quality results in all subjects, and SVs were detected in 14 of them (70%), mostly corresponding to cryptic submicroscopic alterations not observed by standard techniques. Therefore, OGM emerges as a powerful tool that provides complete and evaluable results in hypocellular BMFSs, reducing multiple tests into a single assay and overcoming some of the main limitations of conventional techniques. Furthermore, in addition to confirming the abnormalities detected by conventional techniques, OGM found new alterations beyond their detection limits.
44
Hastie, Alex, Andy W. Pang, and Alka Chaubey. "Abstract 336: Genome integrity assessment by optical genome mapping for cell manufacturing/bioprocessing applications." Cancer Research 84, no. 6_Supplement (2024): 336. http://dx.doi.org/10.1158/1538-7445.am2024-336.
Full textAbstract:
Abstract Cells and cell lines are used for multiple applications such as bioprocessing, therapy, and research. To ensure quality of cells and downstream applications, appropriate quality control (QC) methods are critical. Historically, karyotyping has been employed, but it is limited by its very low resolution and tedious laboratory workflow. Other methods such as PCR and targeted sequencing can characterize only small genomic variants at specific loci. Whole genome sequencing can detect small variants genome-wide but has limited sensitivity in detecting structural variants (SVs). Optical genome mapping (OGM) is a novel genome analysis technique that can fill many of the gaps in current capabilities for assessing genome integrity. To find clonal variants, 400 Gbp of data is collected from the parental/control and test samples. For both samples, a de novo assembly is constructed, and homozygous or heterozygous SVs are assessed. Subsequently, the dual variant annotation pipeline identifies unique SVs in the test sample compared to the parental sample. To discover subclonal SVs down to 5% variant allele fraction (VAF), the workflow leverages the generation of 1.5 Tbp of data, requiring a simple adjustment to longer data collection time. Comparison of test sample to parental sample enables easy determination of acquired variants. Finally, generation of ~5 Tbp of data, requiring 2-3 flowcells to be run, enables the detection of SVs at ultra-low VAF down to ~1%. In this study, several dilutions and simulations were performed to examine OGM’s limit of detection. Targeting a coverage of 5 Tbp and analysis using the somatic SV-analysis workflow revealed that OGM has the sensitivity to detect deletions &gt;50kbp, insertions &gt;20kbp, duplications &gt;100 kbp, and translocations at ~1% VAF. We have applied the clonal and somatic workflows to verify genomes’ integrity after cell immortalization, induced pluripotency, transgene-integration, and gene-editing. The data using the robust and sensitive workflows demonstrate that the OGM platform is a cost-effective solution for cell manufacturing/bioprocessing QC applications. Citation Format: Alex Hastie, Andy W. Pang, Alka Chaubey. Genome integrity assessment by optical genome mapping for cell manufacturing/bioprocessing applications [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 336.
45
Wicks, Stephen J., Marissa Younan, Trilochan Sahoo, et al. "Optical Genome Mapping for Genome-Wide Structural Variation Analysis in Hematologic Malignancies: A Prospective Study Demonstrates Additional Findings Compared to Standard-of-Care (SOC) Cytogenomic Methods." Blood 142, Supplement 1 (2023): 2834. http://dx.doi.org/10.1182/blood-2023-186685.
Full textAbstract:
Genomic structural variants (SVs) are key in understanding the pathogenesis of hematologic malignancies. The current standard-of-care (SOC) cytogenomic methods, including chromosome karyotyping (KT) and fluorescence in situ hybridization (FISH), have inherent limitations in identifying SVs, while next-generation sequencing technologies have limited ability to detect most SVs. Optical Genome Mapping (OGM) is a high-resolution cytogenomic technique that overcomes the limitations of SOC cytogenomic methods and detects all classes of SVs. Recent studies, mostly retrospective, have demonstrated OGM's analytic validity and clinical utility for detecting SVs in both hematologic malignancies and constitutional genetic disorders. This prospective study, using OGM as a validated laboratory developed test (LDT) for detection of SVs, included 112 patients with a wide variety of hematologic malignancies undergoing clinical evaluation and management and demonstrates OGM as superior to SOC cytogenomic methods. Patient blood or bone marrow samples were subject to the Bionano OGM-Dx™ HemeOne assay. OGM analysis was successful for 105/112 (94%) samples with 7/112 (6%) samples failing analysis. Of the 105 analyzed samples, 74 (70%) had abnormal and 31 (30%) had normal findings by OGM analysis, with 49% of abnormal OGM findings classified as complex. At initial diagnosis, 49 cases had guideline and SOC result-based disease risk stratification with 18/49 (37%) graded as high risk, 15/49 (31%) as intermediate risk, and 16/49 (32%) as low risk. Additionally, 60 cases had SOC cytogenomic analysis (KT or FISH) results available; 37% with KT and FISH, 27% with only KT, and 35% with only FISH. OGM cases with normal findings were concordant with KT in 9/10 (90%) of cases and FISH in 8/12 (67%) of cases. For those cases that had abnormal findings by KT and/or FISH, OGM detected additional cytogenomic findings in 79% of cases. A change of risk stratification was made in 12/42 (29%) of cases with additional findings by OGM analysis compared to KT and/or FISH; 9/12 (75%) with upgraded risk and 3/12 (25%) with downgraded risk stratification. In 10/42 (24%) of cases, OGM findings resulted in a change in therapeutic management recommendations. This is exemplified by an acute lymphoblastic leukemia case: KT detected a sole t(9;22) abnormality however, OGM detected t(9;22) and additional findings of gains at chromosomes 1q, 17q, and 19p and losses at chromosomes 5q, 7p, and 11q (see figure 1), changing the risk stratification from intermediate to adverse and directly leading to a change in therapeutic management. The impact of OGM on disease risk stratification and case management is in alignment with previously published studies with OGM analysis demonstrating its power to detect additional findings not seen by SOC cytogenomic analysis. The prospective study outcomes suggest a significant role for OGM in delivering comprehensive results for improved diagnostic assessment and significant prognostic information for better case management and care compared to SOC cytogenomic methods.
46
Ke, Xiaoan, Hongbo Yang, Hui Pan, et al. "The Application of Optical Genome Mapping (OGM) in Severe Short Stature Caused by Duplication of 15q14q21.3." Genes 14, no. 5 (2023): 1016. http://dx.doi.org/10.3390/genes14051016.
Full textAbstract:
(1) Background: Optical genome mapping (OGM) is a novel approach to identifying genomic structural variations with high accuracy and resolution. We report a proband with severe short stature caused by 46, XY, der (16) ins (16;15) (q23; q21.3q14) that was detected by OGM combined with other tests and review the clinical features of patients with duplication within 15q14q21.3; (2) Methods: OGM, whole exon sequencing (WES), copy number variation sequencing (CNV-seq), and karyotyping were used; (3) Results: The proband was a 10.7-year-old boy with a complaint of severe short stature (−3.41SDS) and abnormal gait. He had growth hormone deficiency, lumbar lordosis, and epiphyseal dysplasia of both femurs. WES and CNV-seq showed a 17.27 Mb duplication of chromosome 15, and there was an insertion in chromosome 16 found by karyotyping. Furthermore, OGM revealed that duplication of 15q14q21.3 was inversely inserted into 16q23.1, resulting in two fusion genes. A total of fourteen patients carried the duplication of 15q14q21.3, with thirteen previously reported and one from our center, 42.9% of which were de novo. In addition, neurologic symptoms (71.4%,10/14) were the most common phenotypes; (4) Conclusions: OGM combined with other genetic methods can reveal the genetic etiology of patients with the clinical syndrome, presenting great potential for use in properly diagnosing in the genetic cause of the clinical syndrome.
47
McGinnis, Eric, Ryan J. Stubbins, Dan Li, Zeid Hamadeh, and Tara J. Spence. "Optical Genome Mapping As Standard-of-Care in Acute Leukemia: Diagnostic and Clinical Impacts 10 Months Post-Implementation." Blood 144, Supplement 1 (2024): 1538. https://doi.org/10.1182/blood-2024-208948.
Full textAbstract:
Optical genome mapping (OGM) is a novel cytogenomic method which uses fluorescent labeling, imaging, and reference alignment of high molecular weight DNA for detection of structural and copy number variants at much higher resolution than is attainable using standard cytogenetic assays (karyotyping and FISH; CG). Our clinical laboratory in British Columbia, Canada's largest tertiary care hospital implemented OGM as front-line standard-of-care testing for all newly diagnosed acute leukemias in parallel with CG. We describe the performance and impact on diagnosis and risk stratification of clinical OGM in a prospective cohort of patients for whom OGM was performed in a 10-month period. 90 adults (mean age 55 years, 47% female) with acute leukemia had OGM performed at diagnosis, including 62 with acute myeloid leukemia (AML), 27 with lymphoblastic leukemia, including 22 B lineage (B-ALL) and 5 T lineage (T-ALL), and one mixed phenotype acute leukemia (T/myeloid). OGM was performed per manufacturer protocols on bone marrow aspirate or, when unavailable, blood using a Bionano Saphyr instrument and Rare Variant Analysis informatics (paired with De Novo or Guided Assembly for ALL). Detected variants were filtered using population thresholds and a custom 277-gene/region file and validated laboratory protocols for variant identification and classification in indication-specific contexts. OGM provided adequate data for reporting for 88 individuals (98%) with a mean time to availability of results of 11.8 calendar days following sample procurement. Both instances of OGM failure resulted from inadequate bone marrow aspirate volume and insufficient circulating disease for processing. 201 reportable OGM variants were identified in 61 specimens (69%) compared to 132 identified by CG; specimens with reportable variants averaged 3.3 detected by OGM versus 2 by CG. Additional variants were observed at higher frequency in B-ALL and T-ALL (mean 3.4 and 3 additional variants per) than in AML (0.6 additional variants per), mostly accounted for by recurrent microdeletions. The great majority of specimens with no reportable OGM variants were AML with recurrent diagnostic mutations (44% NPM1, 15% CEBPA, 4% DDX41, 22% myelodysplasia-related). The assigned pathologic diagnosis was changed by OGM in 10 (11%) instances: 9 (15%) AML (3 MECOM rearrangements, 2 NUP98 rearrangements, 2 RUNX1 deletions, an unbalanced 7q rearrangement, and a confirmed constitutional exonic CHEK2 deletion) and 1 (5%) B-ALL with ZNF384 rearrangement. Additional variants predicting increased risk were identified in 12 (19%) individuals with AML (in addition to the above-described variants 5 KMT2A partial tandem duplications) and in 11 (50%) with B-ALL (11 with IKZF1 deletion, 1 with complex karyotype). OGM identified 8 recurrent rearrangements which CG failed to detect (owing either to their cryptic nature or to limitations inherent to techniques), including: MECOM::MYC, NUP98::NSD1, and ETV6::NTRK3 in AML; DDX3X::MLLT10, NOTCH1 deregulation, and HOXA::TCL1A in T-ALL; and IGH::CEBPB, IGH::TRA, FLT3::PAN3, TCF3::ZNF384, and TRA/D::MYB in B-ALL. 3 previously undescribed cryptic driver rearrangements were identified, including MECOM::IL12A-AS1/TRIM59-IFT80 resulting from inv(3)(q25.33q26.2) in AML, MECOM::AL589693.1 resulting from an unbalanced ins(6;3)(q25.3;q26.2q26.2) in oligoblastic AML, and MYB::HACE1 resulting from nested inversions on a der(6)inv(6)(q16.3q16.3)inv(6)(q16.3q23.3) in acute basophilic leukemia (the latter of which appears to phenocopy rare recurrent MYB rearrangements in infant basophilic leukemia). This prospective cohort demonstrates the practicality and real-world clinical impacts of routine clinical genomic profiling of acute leukemia using OGM. Genome-wide high-resolution cytogenomic profiling enables timely and generally unbiased detection of somatic variants of critical value for appropriate diagnosis and risk stratification in the genomic era and circumvents limitations, such as low resolution and reliance on cell division in culture, inherent to current gold-standard CG. Data regarding the prognostic impact and actionability of recurrent variants now routinely detectable by OGM (e.g. FLT3::PAN3 rearrangements identified in 10% of B-ALL in this cohort) are urgently needed to maximally leverage this potentially transformative technology.
48
Klausner, Melanie, Victoria Stinnett, Jen Ghabrial, et al. "Optical Genome Mapping Reveals Complex and Cryptic Rearrangement Involving PML::RARA Fusion in Acute Promyelocytic Leukemia." Genes 15, no. 11 (2024): 1402. http://dx.doi.org/10.3390/genes15111402.
Full textAbstract:
Background/objectives: Acute promyelocytic leukemia (APL) is an aggressive subtype of acute myeloid leukemia (AML), characterized by the hallmark translocation t(15;17) resulting in a PML::RARA fusion. Once diagnosed, APL is now considered to be one of the most treatable forms of AML. However, without early detection and treatment, the disease is associated with rapid deterioration and lethal side effects. Methods: We describe a case of diagnostic APL presenting with a normal karyotype, normal RARA break-apart FISH, and unclear, atypical PML/RARA FISH findings. We used optical genome mapping (OGM) to characterize this atypical PML/RARA fusion. Results: OGM allowed for detection of a PML::RARA fusion resulting from a cryptic and complex insertion of PML::RARA into RARA on 17q21.2 whereby a segment of 15q24.1 was inserted into the 17q21.2. The recipient breakpoint of the insertion was at intron 2 of the RARA gene and the donor breakpoint of the insertion was at exon 5/intron 6 of the PML gene. Conclusions: This is the first report of an insertional PML::RARA fusion into the RARA gene on 17q detected by OGM. OGM has demonstrated its utility in a clinical cytogenetics environment, allowing for clearer characterization and diagnosis of various neoplasms.
49
Berenguer-Rubio, Alejandro, Esperanza Such, Neus Torres Hernández, et al. "Exploring the Potential of Optical Genome Mapping in the Diagnosis and Prognosis of Soft Tissue and Bone Tumors." International Journal of Molecular Sciences 26, no. 6 (2025): 2820. https://doi.org/10.3390/ijms26062820.
Full textAbstract:
Sarcomas are rare malignant tumors of mesenchymal origin with a high misdiagnosis rate due to their heterogeneity and low incidence. Conventional diagnostic techniques, such as Fluorescence In Situ Hybridization (FISH) and Next-Generation Sequencing (NGS), have limitations in detecting structural variations (SVs), copy number variations (CNVs), and predicting clinical behavior. Optical genome mapping (OGM) provides high-resolution genome-wide analysis, improving sarcoma diagnosis and prognosis assessment. This study analyzed 53 sarcoma samples using OGM. Ultra-high molecular weight (UHMW) DNA was extracted from core and resection biopsies, and data acquisition was performed with the Bionano Saphyr platform. Bioinformatic pipelines identified structural variations, comparing them with known alterations for each sarcoma subtype. OGM successfully analyzed 62.3% of samples. Diagnostic-defining alterations were found in 95.2% of cases, refining diagnoses and revealing novel oncogenic and tumor suppressor gene alterations. The challenges included DNA extraction and quality issues from some tissue samples. Despite these limitations, OGM proved to be a powerful diagnostic and predictive tool for bone and soft tissue sarcomas, surpassing conventional methods in resolution and scope, enhancing the understanding of sarcoma genetics, and enabling better patient stratification and personalized therapies.
50
Quesada, Andres E., Gokce A. Toruner, Zhenya Tang, et al. "Optical Genomic Mapping Provides Unique Findings in Various Types of Myeloid Neoplasms." Blood 142, Supplement 1 (2023): 4303. http://dx.doi.org/10.1182/blood-2023-177803.
Full textAbstract:
Introduction: Cytogenomic abnormalities are integral to disease classification, risk stratification, and treatment plans for patients with myeloid neoplasms (MNs). Standard cytogenetic (SCG) techniques, including chromosomal analysis (karyotyping) and fluorescence in situ hybridization (FISH), both carry limitations in detecting certain cytogenomic abnormalities, such as chromoanagenesis, a genomic catastrophe that results in extensive chromosomal rearrangements and copy number alterations. Optical genomic mapping (OGM) is a novel, non-sequencing technique that allows for high-resolution genome wide detection of all classes of structural variants (SVs) and copy number variants (CNVs). This study aimed to investigate cytogenomic alterations across different types of MNs and evaluate the added value of OGM alongside SCG in this context. Materials and methods: OGM was performed using Saphyr from Bionano Genomics (San Diego, USA) on blood or bone marrow from 146 patients diagnosed with various types of MNs over a 9-month period. All patients had karyotype and/or FISH results available. Cases were considered concordant if OGM and SCG both showed normal results or essentially identical cytogenetic abnormalities. Cases were summarized under ‘SCG only’ or ‘OGM only’ if abnormalities were detected by only one assay. Only Tier 1 (pathogenic) and Tier 2 (likely pathogenic) variants were included for a comparison purpose. Abnormalities leading to changes in disease classification, risk stratification, and/or potential patient management were considered as clinically significant. Of note: AML with PML::RARA, RUNX1T1::RUNX1 or MYH11::CBFB rearrangement identified during the fast FISH screen were not included in this study. Results: This study cohort included 90 AML, 26 myelodysplastic syndrome (MDS), 18 myeloproliferative neoplasms (MPN) and 11 MDS/MPN. Overall, 44 (30%) patients showed normal results and 47 (32%) patients showed completely matched cytogenomic abnormalities by OGM and SCG, the remaining 54 (37%) cases showed abnormalities detected by only one assay. Within these 54 cases there were 65 abnormalities detected by only one modality, 11 by SCG only and 54 by OGM only ( Table 1). Of them, 42 were clinically significant: 4 detected by SCG only (in 4 patients) and 38 by OGM only (in 37 patients) ( Table 2). The abnormalities that were detected by SCG but not by OGM were mainly clones or subclones of small (&lt;20%) clonal size, which were below the limit of OGM detection, except one case with tetraploidy in a large clone (65%). The abnormalities detected by OGM but not by SCG mainly included chromoanagenesis (n=17), KMT2A partial tandem duplications (PTD, n=6), chromosomal /gene rearrangement (-R), thirteen being clinically significant: MECOM-R(n=4) , KMT2A-R(n=2) , JAK2-R (n=2) and 5 others in a single case each. Among the various types of MNs, OGM provided additional clinically relevant cytogenomic information in 28 (31%) patients with AML, 8 (31%) patients with MDS, 2 (18%) patients with MDS/MPN, and none (0%) with MPN. Conclusions: Overall, the cytogenomic results completely matched between OGM and SCG in 62% of patients with MNs. The high concordance results seen in MPN suggests OGM may not provide significant additional insight in this setting. OGM identified additional clinically relevant abnormalities in approximately 26% of patients in this cohort. The abnormalities detected by OGM, notably included chromoanagenesis and KMT2A PTDs, were found to occur more frequently in AML and MDS. These abnormalities, undetectable by SCG, are crucial to identify due to their association with significantly poorer prognosis. Additionally, certain abnormalities such as MECOM-R, KMT2A-R, and JAK2-R could potentially guide different therapeutic strategies.