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

• Published in: Cancer research and treatment Vol. 52; no. 1; pp. 41 - 50
• Main Authors: Shin, Hyemi, Sa, Jason K., Bae, Joon Seol, Koo, Harim, Jin, Seonwhee, Cho, Hee Jin, Choi, Seung Won, Kyoung, Jong Min, Kim, Ja Yeon, Seo, Yun Jee, Joung, Je-Gun, Kim, Nayoung K. D., Son, Dae-Soon, Chung, Jongsuk, Lee, Taeseob, Kong, Doo-Sik, Choi, Jung Won, Seol, Ho Jun, Lee, Jung-Il, Suh, Yeon-Lim, Park, Woong-Yang, Nam, Do-Hyun
• Format: Journal Article
• Language: English
• Published: Korea (South) Korean Cancer Association 01.01.2020; 대한암학회
• Subjects: Alleles; Biomarkers, Tumor; Diagnosis, Differential; DNA Copy Number Variations; Female; Gene Frequency; Genetic Association Studies; Genetic Predisposition to Disease; Genetic Testing - methods; Genomics - methods; Glioma - diagnosis; Glioma - genetics; High-Throughput Nucleotide Sequencing - methods; Humans; Immunohistochemistry; In Situ Hybridization, Fluorescence; Male; Mutation; Original; Whole Exome Sequencing; 의학일반; Glioma; Precision medicine; Targeted sequencing; Cancer panel
• ISSN: 1598-2998; 2005-9256; 2005-9256
• DOI: 10.4143/crt.2019.036

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. 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. 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. 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.