Dataset Information

Clinical Targeted Next-Generation sequencing Panels for Detection of Somatic Variants in Gliomas.

ABSTRACT: PURPOSE:Targeted next-generation sequencing (NGS) panels for solid tumors have been useful in clinical framework for accurate tumor diagnosis and identifying essential molecular aberrations. However, most cancer panels have been designed to address a wide spectrum of pan-cancer models, lacking integral prognostic markers that are highly specific to gliomas. Materials and Methods:To address such challenges, we have developed a glioma-specific NGS panel, termed "GliomaSCAN," that is capable of capturing single nucleotide variations and insertion/deletion, copy number variation, and selected promoter mutations and structural variations that cover a subset of intron regions in 232 essential glioma-associated genes. We confirmed clinical concordance rate using pairwise comparison of the identified variants from whole exome sequencing (WES), immunohistochemical analysis, and fluorescence in situ hybridization. RESULTS:Our panel demonstrated high sensitivity in detecting potential genomic variants that were present in the standard materials. To ensure the accuracy of our targeted sequencing panel, we compared our targeted panel to WES. The comparison results demonstrated a high correlation. Furthermore, we evaluated clinical utility of our panel in 46 glioma patients to assess the detection capacity of potential actionable mutations. Thirty-two patients harbored at least one recurrent somatic mutation in clinically actionable gene. CONCLUSION:We have established a glioma-specific cancer panel. GliomaSCAN highly excelled in capturing somatic variations in terms of both sensitivity and specificity and provided potential clinical implication in facilitating genome-based clinical trials. Our results could provide conceptual advance towards improving the response of genomically guided molecularly targeted therapy in glioma patients.

SUBMITTER: Shin H

PROVIDER: S-EPMC6962483 | biostudies-literature | 2020 Jan

REPOSITORIES: biostudies-literature

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Publications

Clinical Targeted Next-Generation sequencing Panels for Detection of Somatic Variants in Gliomas.

Shin Hyemi H Sa Jason K JK Bae Joon Seol JS Koo Harim H Jin Seonwhee S Cho Hee Jin HJ Choi Seung Won SW Kyoung Jong Min JM Kim Ja Yeon JY Seo Yun Jee YJ Joung Je-Gun JG Kim Nayoung K D NKD Son Dae-Soon DS Chung Jongsuk J Lee Taeseob T Kong Doo-Sik DS Choi Jung Won JW Seol Ho Jun HJ Lee Jung-Il JI Suh Yeon-Lim YL Park Woong-Yang WY Nam Do-Hyun DH

Cancer research and treatment 20190507 1

<h4>Purpose</h4>Targeted next-generation sequencing (NGS) panels for solid tumors have been useful in clinical framework for accurate tumor diagnosis and identifying essential molecular aberrations. However, most cancer panels have been designed to address a wide spectrum of pan-cancer models, lacking integral prognostic markers that are highly specific to gliomas.<h4>Materials and methods</h4>To address such challenges, we have developed a glioma-specific NGS panel, termed "GliomaSCAN," that is ...[more]

PMID: 31096737

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Project description:BackgroundWith the expanded availability of next generation sequencing (NGS)-based clinical genetic tests, clinicians seeking to test patients with Mendelian diseases must weigh the superior coverage of targeted gene panels with the greater number of genes included in whole exome sequencing (WES) when considering their first-tier testing approach. Here, we use an in silico analysis to predict the analytic sensitivity of WES using pathogenic variants identified on targeted NGS panels as a reference.MethodsCorresponding nucleotide positions for 1533 different alterations classified as pathogenic or likely pathogenic identified on targeted NGS multi-gene panel tests in our laboratory were interrogated in data from 100 randomly-selected clinical WES samples to quantify the sequence coverage at each position. Pathogenic variants represented 91 genes implicated in hereditary cancer, X-linked intellectual disability, primary ciliary dyskinesia, Marfan syndrome/aortic aneurysms, cardiomyopathies and arrhythmias.ResultsWhen assessing coverage among 100 individual WES samples for each pathogenic variant (153,300 individual assessments), 99.7% (n = 152,798) would likely have been detected on WES. All pathogenic variants had at least some coverage on exome sequencing, with a total of 97.3% (n = 1491) detectable across all 100 individuals. For the remaining 42 pathogenic variants, the number of WES samples with adequate coverage ranged from 35 to 99. Factors such as location in GC-rich, repetitive, or homologous regions likely explain why some of these alterations were not detected across all samples. To validate study findings, a similar analysis was performed against coverage data from 60,706 exomes available through the Exome Aggregation Consortium (ExAC). Results from this validation confirmed that 98.6% (91,743,296/93,062,298) of pathogenic variants demonstrated adequate depth for detection.ConclusionsResults from this in silico analysis suggest that exome sequencing may achieve a diagnostic yield similar to panel-based testing for Mendelian diseases.

Dataset Information

Clinical Targeted Next-Generation sequencing Panels for Detection of Somatic Variants in Gliomas.

Publications

Clinical Targeted Next-Generation sequencing Panels for Detection of Somatic Variants in Gliomas.

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