Feasibility of Optical Genome Mapping in Cytogenetic Diagnostics of Hematological Neoplasms: A New Way to Look at DNA

Diagnostics, Journal Year: 2023, Volume and Issue: 13(11), P. 1841 - 1841

Published: May 24, 2023

Optical genome mapping (OGM) is a new genome-wide technology that can reveal both structural genomic variations (SVs) and copy number (CNVs) in single assay. OGM was initially employed to perform assembly research, but it now more widely used study chromosome aberrations genetic disorders human cancer. One of the most useful applications hematological malignancies, where chromosomal rearrangements are frequent conventional cytogenetic analysis alone insufficient, necessitating further confirmation using ancillary techniques such as fluorescence situ hybridization, microarrays, or multiple ligation-dependent probe amplification. The first studies tested efficiency sensitivity for SV CNV detection, comparing heterogeneous groups lymphoid myeloid sample data with those obtained standard diagnostic tests. Most work based on this innovative focused myelodysplastic syndromes (MDSs), acute leukemia (AML), lymphoblastic (ALL), whereas little attention paid chronic lymphocytic (CLL) myeloma (MM), none lymphomas. showed be considered highly reliable method, concordant able detect novel clinically significant SVs, thus allowing better patient classification, prognostic stratification, therapeutic choices malignancies.

Language: Английский

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Optical Genome Mapping Identifies Novel Recurrent Structural Alterations in Childhood ETV6::RUNX1+ and High Hyperdiploid Acute Lymphoblastic Leukemia

HemaSphere, Journal Year: 2023, Volume and Issue: 7(8), P. e925 - e925

Published: July 17, 2023

The mutational landscape of B-cell precursor acute lymphoblastic leukemia (BCP-ALL), the most common pediatric cancer, is not fully described partially because commonly applied short-read next generation sequencing has a limited ability to identify structural variations. By combining comprehensive analysis variants (SVs), single-nucleotide (SNVs), and small insertions-deletions, new subtype-defining therapeutic targets may be detected. We analyzed somatic alterations in 60 patients diagnosed with BCP-ALL subtypes, ETV6::RUNX1 + classical hyperdiploid (HD), using conventional cytogenetics, single nucleotide polymorphism (SNP) array, whole exome (WES), novel optical genome mapping (OGM) technique. Ninety-five percent SVs detected by cytogenetics SNP-array were verified OGM. OGM an additional 677 identified methods, including (subclonal) IKZF1 deletions. Based on OGM, harbored 2.7 times more than HD BCP-ALL, mainly focal Besides known development genes ( ETV6 , PAX5 BTG1, CDKN2A ), we 19 recurrently altered regions (in n ≥ 3) 9p21.3 FOCAD/HACD4 8p11.21 IKBKB 1p34.3 ZMYM1 4q24 MANBA 8p23.1 MSRA 10p14 SFMBT2 as well ETV6::RUNX1+ subtype-specific (12p13.1 GPRC5A 12q24.21 MED13L 18q11.2 MIB1 20q11.22 NCOA6 )). 3 fusion SFMBT2::DGKD, PDS5B::STAG2, TDRD5::LPCAT2 for which sequence expression validated long-read transcriptome sequencing, respectively. WES double hits SNVs BTG1 STAG2 TBL1XR1 NSD2 ) same patient demonstrating power combined approach define genomic BCP-ALL.

Language: Английский

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Optical Genome Mapping Reveals the Complex Genetic Landscape of Myeloma

Cancers, Journal Year: 2023, Volume and Issue: 15(19), P. 4687 - 4687

Published: Sept. 22, 2023

Fluorescence in situ hybridization (FISH) on enriched CD138 plasma cells is the standard method for identification of clinically relevant genetic abnormalities multiple myeloma. However, FISH a targeted analysis that can be challenging due to complexity The aim this study was evaluate potential optical genome mapping (OGM) detect significant cytogenetic myeloma and provide larger pangenomic information. OGM analyses were performed CD138-purified 20 patients. successfully detected structural variants (SVs) (IGH MYC rearrangements), copy number (CNVs) (17p/TP53 deletion, 1p deletion 1q gain/amplification) aneuploidy (gains odd-numbered chromosomes, monosomy 13) classically expected with led 30% increase prognosis yield at our institution when compared FISH. Despite challenges interpretation calls CNV losses non-diploid genomes, has replace as care clinical settings efficiently change how we identify prognostic predictive markers therapies future. To knowledge, first highlighting feasibility utility

Language: Английский

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Exome Sequencing and Optical Genome Mapping in Molecularly Unsolved Cases of Duchenne Muscular Dystrophy: Identification of a Causative X-Chromosomal Inversion Disrupting the DMD Gene

International Journal of Molecular Sciences, Journal Year: 2023, Volume and Issue: 24(19), P. 14716 - 14716

Published: Sept. 28, 2023

Duchenne muscular dystrophy (DMD) is a severe progressive muscle disease that mainly affects boys due to X-linked recessive inheritance. In most affected individuals, MLPA or sequencing-based techniques detect deletions, duplications, point mutations in the dystrophin-encoding DMD gene. However, small subset of patients clinically diagnosed with DMD, molecular cause not identified these routine methods. Evaluation 60 our center revealed three cases without known genetic cause. DNA samples were analyzed using whole-exome sequencing (WES) and, if unconclusive, optical genome mapping (OGM). WES led diagnosis two cases: one patient was found carry splice mutation gene had been during previous Sanger sequencing. second patient, we detected variants fukutin (FKTN) presumed be disease-causing. third unremarkable, but OGM an inversion disrupting (~1.28 Mb) subsequently confirmed long-read These results highlight importance reanalyzing unsolved and demonstrate useful method for identifying large structural unremarkable exome

Language: Английский

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Optical genome mapping for detection of chromosomal aberrations in prenatal diagnosis

Acta Obstetricia Et Gynecologica Scandinavica, Journal Year: 2023, Volume and Issue: 102(8), P. 1053 - 1062

Published: June 27, 2023

Abstract Introduction Chromosomal aberrations are the most important etiological factors for birth defects. Optical genome mapping is a novel cytogenetic tool detecting broad range of chromosomal in single assay, but relevant clinical feasibility studies optical prenatal diagnosis limited. Material and methods We retrospectively performed analysis amniotic fluid samples from 34 fetuses with various indications detected through standard‐of‐care technologies, including karyotyping, fluorescence situ hybridization, and/or microarray analysis. Results In total, we analyzed 46 samples, 5 aneuploidies, 10 large copy number variations, 27 microdeletions/microduplications, 2 translocations, 1 isochromosome, region homozygosity. Overall, 45 could be confirmed by our customized strategy. reached 97.8% concordant all blinded fashion. Compared widely used analysis, additionally determined relative orientation position repetitive segments seven cases duplications or triplications. The additional information provided will conducive to characterizing complex rearrangements allowing us propose mechanisms explain predict genetic recurrence risk. Conclusions Our study highlights that can provide comprehensive accurate on test, suggesting has potential become promising diagnosis.

Language: Английский

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Novel NUP98::ASH1L Gene Fusion in Acute Myeloid Leukemia Detected by Optical Genome Mapping

Cancers, Journal Year: 2023, Volume and Issue: 15(11), P. 2942 - 2942

Published: May 27, 2023

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 detection of genome-wide structural variants and disease monitoring. A previously unrecognized NUP98::ASH1L fusion detected an adult patient with secondary AML. identified NUP98 Absent, Small, or Homeotic-Like Histone Lysine Methyltransferase (ASH1L) result complex rearrangement between chromosomes 1 11. pipeline measurement rare (Rare Variant Pipeline, Bionano Genomics, San Diego, CA, USA) used detection. As other fusions are relevant classification, demonstrates necessity methods such cytogenetic Furthermore, showed discordant variant allele frequencies at different time points over course treatment pressure, indicating clonal evolution. These results support be valuable primary AML well longitudinal testing monitoring deepening our understanding genetically heterogenous diseases.

Language: Английский

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Variant allele fraction or copy-neutral loss of heterozygosity? A comparison of testing platforms in the classification of myeloid neoplasia

Journal of Hematopathology, Journal Year: 2025, Volume and Issue: 18(1)

Published: April 23, 2025

Language: Английский

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Clinical Utility of Optical Genome Mapping as an Additional Tool in a Standard Cytogenetic Workup in Hematological Malignancies

Cancers, Journal Year: 2025, Volume and Issue: 17(9), P. 1436 - 1436

Published: April 25, 2025

Background and Objective: The primary objective of this study is to evaluate the added value optical genome mapping (OGM) when integrated into standard cytogenetic workup (SCGW) for hematological malignancies. Methods: cohort comprised 519 cases with different types OGM SCGW (including G-banded karyotyping fluorescence in situ hybridization) were performed on blood and/or bone marrow. analytical sensitivity OGM, defined as detection all additional cytogenomic aberrations, its clinical utility, referring aberrations diagnostic, prognostic, or therapeutic significance, assessed. Results: led increased utility 58% 15% cases, respectively. varied across malignancies, highest T-lymphoblast leukemia (52%), followed by mixed phenotype acute (43%), B-lymphoblastic (37%), other B-cell lymphomas (22%), mature T-cell leukemia/lymphoma (20%), chronic lymphocytic (14%), myeloid (13%), multiple myeloma mantle cell lymphoma (8%), myelodysplastic/myeloproliferative neoplasms (6%), myelodysplastic syndrome (5%), myeloproliferative (0%). Conclusion: Compared SCGW, detects approximately cases. provides at varying rates Given these differences, strategic triaging can help maximize focusing diseases where it offers most significant benefit.

Language: Английский

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Integration of Optical Genome Mapping in the Cytogenomic and Molecular Work‐Up of Hematological Malignancies: Expert Recommendations From the International Consortium for Optical Genome Mapping

American Journal of Hematology, Journal Year: 2025, Volume and Issue: unknown

Published: April 30, 2025

ABSTRACT The latest updates to the classification of hematolymphoid malignancies using World Health Organization (WHO, 5th ed.) and ICC (International Consensus Classification) criteria highlight critical need for comprehensive precise cytogenomic data diagnosis, prognostication, treatment. This presents significant challenges clinical laboratories, requiring a complex workflow multiple assays detect different types structural chromosomal variants (copy number changes, fusions, inversions) across entire genome. Optical genome mapping (OGM) is an advanced tool genome‐wide detection alterations at gene/exon level. Studies demonstrate that OGM facilitates identification novel biomarkers, improves risk stratification, expands therapeutic targets personalized treatment strategies. easy implement highly accurate in detecting (SVs) various diagnostic entities. Consequently, many centers are integrating into cytogenetic hematological malignancies. However, systemic adoption has remained limited due lack expert recommendations on indications, testing algorithms, result interpretation. To address this, experts from International Consortium relevant multidisciplinary fields developed integration as standard‐of‐care assay settings. These standardize use ensure high‐quality data, guide trial design development, provide basis models.

Language: Английский

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Optical genome mapping for prenatal diagnosis: A prospective study

Clinica Chimica Acta, Journal Year: 2023, Volume and Issue: 551, P. 117594 - 117594

Published: Oct. 11, 2023

Language: Английский

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