Variant calling and benchmarking in an era of complete human genome sequences

Nature Reviews Genetics, Journal Year: 2023, Volume and Issue: 24(7), P. 464 - 483

Published: April 14, 2023

Language: Английский

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Optical genome mapping for structural variation analysis in hematologic malignancies

American Journal of Hematology, Journal Year: 2022, Volume and Issue: 97(7), P. 975 - 982

Published: May 13, 2022

Optical genome mapping (OGM) is a technology that rapidly being adopted in clinical genetics laboratories for its ability to detect structural variation (e.g., translocations, inversions, deletions, duplications, etc.) and replace several concurrent standard of care techniques (karyotype, fluorescence situ hybridization, chromosomal microarray). OGM can dramatically simplify lab workflow by reducing multiple tests (conventional karyotype, hybridization [FISH], microarray) into one test. The superior across the removes need reflex FISH studies, which reduce cost turnaround time per sample. Parallel studies versus testing have demonstrated it resolve more abnormalities than karyotyping or FISH. However, like many molecular normalize copy number difficulty with non-diploid karyotypes. This Test Month review will summarize how technique works, strengths weaknesses compared illustrate likely change front line hematologic malignancies-including summarizing utility acute myeloid leukemia, myelodysplastic syndromes, B cell lymphoblastic leukemia.

Language: Английский

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Optical Genome Mapping for Cytogenetic Diagnostics in AML

Cancers, Journal Year: 2023, Volume and Issue: 15(6), P. 1684 - 1684

Published: March 9, 2023

The classification and risk stratification of acute myeloid leukemia (AML) is based on reliable genetic diagnostics. A broad expanding variety relevant aberrations are structural variants beyond single-nucleotide variants. Optical Genome Mapping an unbiased, genome-wide, amplification-free method for the detection In this review, current knowledge (OGM) with regard to diagnostics in hematological malignancies general, AML specific, summarized. Furthermore, review focuses ability OGM expand use cytogenetic perhaps even replace older techniques such as chromosomal-banding analysis, fluorescence situ hybridization, or copy number variation microarrays. Finally, compared amplification-based a brief outlook future directions given.

Language: Английский

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A framework for the clinical implementation of optical genome mapping in hematologic malignancies

American Journal of Hematology, Journal Year: 2024, Volume and Issue: 99(4), P. 642 - 661

Published: Jan. 2, 2024

Optical Genome Mapping (OGM) is rapidly emerging as an exciting cytogenomic technology both for research and clinical purposes. In the last 2 years alone, multiple studies have demonstrated that OGM not only matches diagnostic scope of conventional standard care testing but it also adds significant new information in certain cases. Since consolidates benefits costly laborious tests (e.g., karyotyping, fluorescence situ hybridization, chromosomal microarrays) a single cost-effective assay, many laboratories started to consider utilizing OGM. 2021, international working group early adopters who are experienced with routine patients hematological neoplasms formed consortium (International Consortium Hematologic Malignancies, henceforth "the Consortium") create consensus framework implementation setting. The focus provide guidance implementing three specific areas: validation, quality control analysis interpretation variants. complex variables, we felt by consolidating our collective experience, could practical useful tool uniform hematologic malignancies ultimate goal achieving globally accepted standards.

Language: Английский

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Structural Variant Analysis of Complex Karyotype Myelodysplastic Neoplasia Through Optical Genome Mapping

Genes Chromosomes and Cancer, Journal Year: 2025, Volume and Issue: 64(1)

Published: Jan. 1, 2025

ABSTRACT Myelodysplastic neoplasia with complex karyotype (CK‐MDS) poses significant clinical challenges and is associated poor survival. Detection of structural variants (SVs) crucial for diagnosis, prognostication, treatment decision‐making in MDS. However, the current standard‐of‐care (SOC) cytogenetic testing, relying on karyotyping, often yields ambiguous results cases CK. Here, SV detection by novel optical genome mapping (OGM) technique was explored 15 CK‐MDS cases, which collectively harbored 85 chromosomes abnormalities reported SOC. Additionally, OGM utilized discovery SVs. Altogether, detected corresponding > 5 Mbp alterations 73 out SOC abnormalities, resulting an 86% concordance rate. provided further specification these revealing that 64% altered were affected multiple SVs or chromoanagenesis. Prominently, only 5% missing true monosomies. In addition, not as abnormal karyotyping 93% clinically relevant gene‐level information, such TP53 , MECOM NUP98 IKZF1 ETV6 . Analysis revealed two previously unreported gene‐fusions ( SCFD1::ZNF592 VPS8::LRBA ), both confirmed transcriptome sequencing. Furthermore, repositioning CCDC26 (8q24.21) identified a potential cause inappropriate gene activation affecting SOX7 respectively. This study shows can significantly enhance diagnostic analysis highlights utility identifying cancer genomes.

Language: Английский

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Optical Genome Mapping: A Promising New Tool to Assess Genomic Complexity in Chronic Lymphocytic Leukemia (CLL)

Cancers, Journal Year: 2022, Volume and Issue: 14(14), P. 3376 - 3376

Published: July 11, 2022

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 (CMA). Optical genome mapping (OGM), a novel technique based on imaging long DNA molecules labeled at specific sites, allows identification multiple cytogenetic abnormalities single test. We aimed to determine whether OGM is suitable alternative cytogenomic assessment CLL, especially focused complexity. Cytogenomic aberrations from 42 patients were compared with CBA, FISH, CMA information. Clinical–biological characteristics time first treatment (TTFT) analyzed according complexity detected OGM. Globally, identified 90.3% known alterations (279/309). Discordances mainly found (peri-)centromeric or telomeric regions subclonal (<15–20%). underscored additional abnormalities, providing structural information 55% patients. Regarding number had better accuracy predicting TTFT than current methods (C-index: 0.696, 0.602, 0.661 OGM, CMA, respectively). A cut-off ≥10 defined complex group (C-OGM, n = 12), which included 11/14 ≥5 CBA/CMA one patient chromothripsis (Kappa index 0.778; p < 0.001). Moreover, C-OGM displayed enrichment TP53 (58.3% vs. 3.3%, 0.001) significantly shorter (median: 2 43 months, 0.014). robust technology for implementation routine management CLL patients, although further studies are required define standard criteria.

Language: Английский

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Optical Genome Mapping as an Alternative to FISH-Based Cytogenetic Assessment in Chronic Lymphocytic Leukemia

Cancers, Journal Year: 2023, Volume and Issue: 15(4), P. 1294 - 1294

Published: Feb. 17, 2023

The fluorescence in situ hybridization (FISH) technique plays an important role the risk stratification and clinical management of patients with chronic lymphocytic leukemia (CLL). For genome-wide analysis, FISH needs to be complemented other cytogenetic methods, including karyotyping and/or chromosomal microarrays. However, this is often not feasible a diagnostic setup. Optical genome mapping (OGM) novel for high-resolution detection structural variants (SVs), previous studies have indicated that OGM could serve as generic tool hematological malignancies. Herein, we report results from our study evaluating concordance standard-of-care 18 CLL samples. were fully concordant between these two techniques blinded comparison. Using silico dilution series, lowest limit was determined range 3 9% variant allele fractions. Genome-wide analysis by revealed additional (>1 Mb) aberrations 78% samples, both unbalanced balanced SVs. Importantly, also enabled clinically relevant complex karyotypes, undetectable FISH, three Overall, demonstrates potential first-tier test powerful SV analysis.

Language: Английский

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Optical Genome Mapping as a Diagnostic Tool in Pediatric Acute Myeloid Leukemia

Cancers, Journal Year: 2022, Volume and Issue: 14(9), P. 2058 - 2058

Published: April 19, 2022

Pediatric AML is characterized by numerous genetic aberrations (chromosomal translocations, deletions, insertions) impacting its classification for risk of treatment failure. Aberrations are described classical cytogenetic procedures (karyotyping, FISH), which harbor limitations (low resolution, need cell cultivation, cost-intensiveness, experienced staff required). Optical Genome Mapping (OGM) an emerging chip-based DNA technique combining high resolution (~500 bp) with a relatively short turnaround time. Twenty-four pediatric patients AML, bi-lineage leukemia, and mixed-phenotype acute leukemia were analyzed OGM, the results compared cytogenetics. Results discrepant in 17/24 (70%) cases, including 32 previously unknown alterations called OGM only. One newly detected deletion two translocations validated primer walking, breakpoint-spanning PCR, sequencing. As added benefit, identified new minimal residual disease (MRD) marker. Comparing impact on stratification de novo 19/20 (95%) cases had concordant while only unraveled another high-risk aberration. Thus, considerably expands methodological spectrum to optimize diagnosis via identification aberrations. will contribute better understanding leukemogenesis AML. In addition, may provide markers MRD monitoring.

Language: Английский

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Optical genome mapping refines cytogenetic diagnostics, prognostic stratification and provides new molecular insights in adult MDS/AML patients

Blood Cancer Journal, Journal Year: 2022, Volume and Issue: 12(9)

Published: Sept. 2, 2022

Language: Английский

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Optical Genome Mapping Reveals and Characterizes Recurrent Aberrations and New Fusion Genes in Adult ALL

Genes, Journal Year: 2023, Volume and Issue: 14(3), P. 686 - 686

Published: March 9, 2023

(1) Background: In acute lymphoblastic leukemia (ALL) the genetic characterization remains challenging. Due to heterogeneity of mutations in adult patients, only a small proportion aberrations can be analyzed with standard routine diagnostics. Optical genome mapping (OGM) has recently opened up new possibilities for structural variants on genome-wide level, thus enabling simultaneous analysis broad spectrum aberrations. (2) Methods: 11 ALL patients were examined using OGM. (3) Results: Genetic results obtained by karyotyping and FISH confirmed OGM all patients. Karyotype was redefined, additional information 82% (9/11) samples OGM, previously not diagnosed care. Besides gross-structural chromosome rearrangements, e.g., ring 9 putative isodicentric 8q, deletions CDKN2A/2B detected 7/11 defining an approx. 20 kb minimum region overlap, including alternative exon 1 CDKN2A gene. The further confirm recurrent (e.g., PAX5, ETV6, VPREB1, IKZF1). (4) Conclusions: Genome-wide enables one single workup compared clinical testing, facilitating detailed diagnosis, risk-stratification, target-directed treatment strategies.

Language: Английский

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