Journal of Gastric Cancer

The Korean Gastric Cancer Association (대한위암학회)
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Genetic Characterization of Molecular Targets in Korean Patients with Gastrointestinal Stromal Tumors

  • Park, Joonhong (Department of Laboratory Medicine, College of Medicine, The Catholic University of Korea) ;
  • Yoo, Han Mo (Department of Surgery, College of Medicine, The Catholic University of Korea) ;
  • Sul, Hae Jung (Department of Pathology, College of Medicine, The Catholic University of Korea) ;
  • Shin, Soyoung (Department of Laboratory Medicine, College of Medicine, The Catholic University of Korea) ;
  • Lee, Seung Woo (Division of Gastroenterology, Department of Internal Medicine, College of Medicine, The Catholic University of Korea) ;
  • Kim, Jeong Goo (Department of Surgery, College of Medicine, The Catholic University of Korea)
  • Received : 2019.07.12
  • Accepted : 2019.12.03
  • Published : 2020.03.31
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Abstract

Purpose: Gastrointestinal stromal tumors (GISTs) frequently harbor activating gene mutations in either KIT or platelet-derived growth factor receptor A (PDGFRA) 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. Materials and Methods: 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. Results: 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. KIT variants were most frequent (44%, 19/43), followed by 6 variants in PIK3CA, 3 in PDGFRA, 2 each in JAK1 and EGFR, and 1 each in AKT1, ALK, CCND1, CTNNB1, FGFR3, FGFR4, GNA11, GNAQ, JAK3, MET, and SMO. 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. Conclusions: 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.

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References

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