The known structural variations in hearing loss and their diagnostic approaches: a comprehensive review

Molecular Biology Reports, Journal Year: 2025, Volume and Issue: 52(1)

Published: Jan. 17, 2025

Language: Английский

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A comprehensive approach to evaluate genetic abnormalities in multiple myeloma using optical genome mapping

Blood Cancer Journal, Journal Year: 2024, Volume and Issue: 14(1)

Published: May 3, 2024

Language: Английский

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Clinical Validation of Optical Genome Mapping in Multiple Myeloma Without Plasma Cell Enrichment

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

Published: Jan. 17, 2025

Cytogenetic alterations are important in risk stratification for multiple myeloma (MM). Translocations involving the immunoglobulin heavy chain (IGH), such as t(4;14), t(14;16), well del(17p) and gain(1q), recognized high-risk cytogenetic markers staging systems [1]. Fluorescence situ hybridization (FISH) is primary method detecting these genetic alterations. However, testing MM challenging owing to lower proportion of plasma cells bone marrow (BM) aspirates, which may arise from sample variability or suboptimal quality. To address challenges, clinical laboratories employ CD138+ cell enrichment procedures, cytoplasmic FISH sorting using either flow cytometry magnetic beads. Although techniques can increase analytical sensitivity FISH, they also come with drawbacks, need additional steps, associated costs, time required, larger volumes BM samples. Optical genome mapping (OGM) an emerging technology that offers advantages genome-wide structural variations copy number variants high sensitivities hematologic malignancies [2]. In MM, OGM has revealed promising results compared conventional methods, karyotyping [3, 4]. Moreover, its ability perform high-resolution, analysis, facilitates classification detection not identified by including those MYC gene 5]. Compared whole-genome sequencing, be more cost-effective while achieving higher coverage, directly improving low variant allele frequencies (VAFs). With 300× reported capable VAF ≥ 5%. this study, we evaluated application alterations, routinely performed FISH. Based on a pilot study aspirate samples percentage > 50% without [3], aimed evaluate performance varying percentages enrichment. We identify optimal enable routine settings. This included 25 obtained patients newly diagnosed between January 2023 June 2024 at Guro Hospital, Korea University (Table S1). All had 10% aspirates. Samples concurrent were included. was approved Institutional Review Board (2024GR0240), conducted accordance Declaration Helsinki. previously procedure [5]. Briefly, ultra-high molecular weight DNA aspirates labeled Standard Direct Label Enzyme 1 reaction loaded onto Saphyr chip (Bionano Genomics, San Diego, CA, USA). Images instrument analyzed Bionano Solve/Access software Rare Variant analysis pipeline procedures according manufacturer's protocols, approximately effective reference coverage. Detailed methods provided Data S1. Interphase isolated magnetic-assisted (Miltenyi Biotech, Bisley, UK). Probes used follows: LSI IGH/FGFR3, IGH/MAF, IGH/CCND1 dual-color probe, TP53 (17p13.1)/CEP 17 13 (D13S319) 13q14.3 single-color probe (MetaSystems, MA, USA), 1q21/1p32 (Cytocell Inc., Cambridge, A minimum 200 counted each probe. The cutoff values 1.0% translocations, 2.5% amplification, 3.8% deletions, break-apart signals. compare data, estimated allelic frequency (AF) (termed herein "estimated AF") microscopic examination aspirate. AF calculated multiplying then dividing result 10 000. As detects 5%, < but OGM, considered discordant. explored thresholds examination-derived percentages. expected, consistently yielded than [6] (Figure Given discrepancy, well-established role morphology assessment, primarily based our analysis. Among cases data enumerated cytometry, 38 aberrations detected canonical translocations IGH (CNVs) 1A). aberrations, 10.5% (n = 4) below When considering 5% (34 aberrations), exhibited concordance 98.2% 168/171) across 171 loci tested For revised international system (R-ISS) chromosomal abnormalities (t(4;14), del(17p)), 100% 74/74). second revision ISS (R2-ISS), del(17p), 98.6% 72/73). results, 91.2% 31/34) specificity 137/137) Of 11 (five t(4;14) six t(11;14)), all except one case t(11;14). showed 72.3% abnormality relatively 7.6%, due levels (BM 10.5%). 23 CNVs (10 1q gain, two del(1p), del(13q), could detect CNV both gain del(1p). contrast previous findings, de novo assembly retrieve undetected [4]. explore enrichment, comparing Our 10.0% (flow 1.4%). CNVs, 13.8% 2.2%) 1B). These indicate threshold suggesting translocations. factor sensitivity, influenced results. when morphological 21.0% 3.6%). Conversely, 20.6% 3.3%), improved did full range percentages, represent lowest where detected. Both should detection. reports following significant findings: (1) demonstrated potential particularly overall 98.2%; (2) (an vs. 13.8%); (3) serve minimal reliably Genome-wide beyond targeted five hyperdiploidy, hyperdiploidy four samples, 15.0% (3 20 metaphases) missing (2 (data shown). suggest comparable other Regarding offer solution achieve Future validation studies, repeated measurements VAFs needed fully establish OGM. While findings highlight OGM's complementary initial screening tool settings, careful consideration essential optimize application. Study conceptualization design: J.Y., J.A.K., S.-Y.Y. collection: J.Y. interpretation: J.A.K. Writing manuscript, design figures/tables: authors participated writing review article final submitted version. supported National Research Foundation (NRF) grant funded Korean government (MSIT) (2022R1G1A1007629) Hospital (O2400231). Helsinki exemption patient consent. declare no conflicts interest. sets generated and/or during current available corresponding author upon reasonable request. Figure Comparison cytometry. Table Clinical characteristics Please note: publisher responsible content functionality any supporting information supplied authors. Any queries (other content) directed article.

Language: Английский

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Exploring the Potential of Optical Genome Mapping in the Diagnosis and Prognosis of Soft Tissue and Bone Tumors

International Journal of Molecular Sciences, Journal Year: 2025, Volume and Issue: 26(6), P. 2820 - 2820

Published: March 20, 2025

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) Next-Generation Sequencing (NGS), have limitations in detecting structural variations (SVs), copy number (CNVs), predicting clinical behavior. Optical genome mapping (OGM) provides high-resolution genome-wide analysis, improving sarcoma diagnosis prognosis assessment. This study analyzed 53 samples using OGM. Ultra-high molecular weight (UHMW) DNA was extracted from core resection biopsies, data acquisition performed the Bionano Saphyr platform. Bioinformatic pipelines identified variations, comparing them known alterations for each subtype. OGM successfully 62.3% samples. Diagnostic-defining were found 95.2% cases, refining diagnoses revealing novel oncogenic tumor suppressor gene alterations. The challenges included extraction quality issues some tissue Despite these limitations, proved be powerful predictive tool bone soft sarcomas, surpassing conventional methods resolution scope, enhancing understanding genetics, enabling better patient stratification personalized therapies.

Language: Английский

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Deciphering Genomic Complexity of Multiple Myeloma Using Optimized Optical Genome Mapping

Journal of Molecular Diagnostics, Journal Year: 2025, Volume and Issue: 27(4), P. 306 - 322

Published: March 26, 2025

Language: Английский

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Plasma Cell Enrichment and New Genomic Approaches in Multiple Myeloma: A Scoping Review

The Journal of Applied Laboratory Medicine, Journal Year: 2025, Volume and Issue: unknown

Published: April 18, 2025

Abstract Background Multiple myeloma (MM) is a genetically heterogeneous disease where specific genetic abnormalities have significant impact on patient’s prognosis. Diagnostic and prognostic tools like fluorescence in situ hybridization (FISH), PCR, microarrays, next-generation sequencing (NGS) transformed MM management. However, the effectiveness of these techniques often limited by low concentration plasma cells bone marrow samples, which makes enrichment methods necessary. This review aims to clarify how enhance detection abnormalities, reduce false-negative results, facilitate more precise risk stratification for patients. Content Following Preferred Reporting Items Systematic reviews Meta-Analyses Extension Scoping Review (PRISMA-ScR) guidelines, literature cell separation used studies was systematically identified mapped. Searches were conducted Medline Embase databases using structured strategy, supplemented manual searches Google Scholar. Of 399 publications evaluated, 69 met inclusion criteria; 37% utilized FISH 19% demonstrated an increasing use NGS. Plasma significantly improved diagnostic accuracy, rates from 61% non-enriched samples 95.5% enriched samples. While remains gold standard, emerging technologies such as NGS offer superior sensitivity ability identify critical alterations refine molecular subtypes. Summary Clinically are detected frequently with techniques, contributing prognosis treatment strategies

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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MYC alterations in multiple myeloma: Genetic insights and prognostic impact

Neoplasia, Journal Year: 2025, Volume and Issue: 66, P. 101177 - 101177

Published: May 14, 2025

Language: Английский

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Analytic Validation of Optical Genome Mapping in Hematological Malignancies

Biomedicines, Journal Year: 2023, Volume and Issue: 11(12), P. 3263 - 3263

Published: Dec. 9, 2023

Structural variations (SVs) play a key role in the pathogenicity of hematological malignancies. Standard-of-care (SOC) methods such as karyotyping and fluorescence situ hybridization (FISH), which have been employed globally for past three decades, significant limitations terms resolution number recurrent aberrations that can be simultaneously assessed, respectively. Next-generation sequencing (NGS)-based technologies are now widely used to detect clinically sequence variants but limited their ability accurately SVs. Optical genome mapping (OGM) is an emerging technology enabling genome-wide detection all classes SVs at significantly higher than FISH. OGM requires neither cultured cells nor amplification DNA, addressing culture biases. This study reports clinical validation laboratory-developed test (LDT) according stringent regulatory (CAP/CLIA) guidelines SV different In total, 60 cases with malignancies (of various subtypes), 18 controls, 2 cancer cell lines were this study. Ultra-high-molecular-weight DNA was extracted from samples, fluorescently labeled, run on Bionano Saphyr system. A total 215 datasets, Inc.luding replicates, generated, analyzed successfully. Sample data then using either disease-specific or pan-cancer-specific BED files prioritize calls known diagnostically prognostically relevant. Sensitivity, specificity, reproducibility 100%, 96%, Following validation, 14 10 controls outside laboratories showing 96.4%. found more relevant compared SOC testing due its resolution. The results demonstrate superiority over traditional accurate diagnosis

Language: Английский

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