Genetic Characterization of Molecular Targets in Korean Patients with Gastrointestinal Stromal Tumors

• Published in: Journal of gastric cancer Vol. 20; no. 1; pp. 29 - 40
• Main Authors: Park, Joonhong, Yoo, Han Mo, Sul, Hae Jung, Shin, Soyoung, Lee, Seung Woo, Kim, Jeong Goo
• Format: Journal Article
• Language: English
• Published: Korea (South) The Korean Gastric Cancer Association 01.03.2020; 대한위암학회
• Subjects: Original; 일반외과학; Gastrointestinal stromal tumors; Next-generation sequencing; Mutation; Ion torrent sequencing; KIT gene
• ISSN: 2093-582X; 2093-5641
• DOI: 10.5230/jgc.2020.20.e2

Gastrointestinal stromal tumors (GISTs) frequently harbor activating gene mutations in either or platelet-derived growth factor receptor A ( ) and are highly responsive to several selective tyrosine kinase inhibitors. In this study, a targeted next-generation sequencing (NGS) assay with an Oncomine Focus Assay (OFA) panel was used for the genetic characterization of molecular targets in 30 Korean patients with GIST. Using the OFA that enables rapid and simultaneous detection of hotspots, single nucleotide variants (SNVs), insertion and deletions (Indels), copy number variants (CNVs), and gene fusions across 52 genes relevant to solid tumors, targeted NGS was performed using genomic DNA extracted from formalin-fixed and paraffin-embedded samples of 30 GISTs. Forty-three hotspot/other likely pathogenic variants (33 SNVs, 8 Indels, and 2 amplifications) in 16 genes were identified in 26 of the 30 GISTs. variants were most frequent (44%, 19/43), followed by 6 variants in , 3 in , 2 each in and , and 1 each in , , , , , , , , , , and . Based on the mutation types, majority of the variants carried missense mutations (60%, 26/43), followed by 8 frameshifts, 6 nonsense, 1 stop-loss, and 2 amplifications. Our study confirmed the advantage of using targeted NGS with a cancer gene panel to efficiently identify mutations associated with GISTs. These findings may provide a molecular genetic basis for developing new drugs targeting these gene mutations for GIST therapy.