Genetic Characterization of Molecular Targets in Korean Patients with Gastrointestinal Stromal Tumors
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...
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| Published in | Journal of gastric cancer Vol. 20; no. 1; pp. 29 - 40 |
|---|---|
| Main Authors | , , , , , |
| Format | Journal Article |
| Language | English |
| Published |
Korea (South)
The Korean Gastric Cancer Association
01.03.2020
대한위암학회 |
| Subjects | |
| Online Access | Get full text |
| ISSN | 2093-582X 2093-5641 |
| DOI | 10.5230/jgc.2020.20.e2 |
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| Abstract | 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. |
|---|---|
| AbstractList | 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. KCI Citation Count: 0 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.PURPOSEGastrointestinal 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.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.MATERIALS AND METHODSUsing 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. 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.RESULTSForty-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.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.CONCLUSIONSOur 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. 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. |
| Author | Shin, Soyoung Sul, Hae Jung Kim, Jeong Goo Park, Joonhong Yoo, Han Mo Lee, Seung Woo |
| AuthorAffiliation | 3 Department of Pathology, College of Medicine, The Catholic University of Korea, Seoul, Korea 4 Division of Gastroenterology, Department of Internal Medicine, College of Medicine, The Catholic University of Korea, Seoul, Korea 1 Department of Laboratory Medicine, College of Medicine, The Catholic University of Korea, Seoul, Korea 2 Department of Surgery, College of Medicine, The Catholic University of Korea, Seoul, Korea |
| AuthorAffiliation_xml | – name: 2 Department of Surgery, College of Medicine, The Catholic University of Korea, Seoul, Korea – name: 4 Division of Gastroenterology, Department of Internal Medicine, College of Medicine, The Catholic University of Korea, Seoul, Korea – name: 1 Department of Laboratory Medicine, College of Medicine, The Catholic University of Korea, Seoul, Korea – name: 3 Department of Pathology, College of Medicine, The Catholic University of Korea, Seoul, Korea |
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| Keywords | Gastrointestinal stromal tumors Next-generation sequencing Mutation Ion torrent sequencing KIT gene |
| Language | English |
| License | Copyright © 2020. Korean Gastric Cancer Association. This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (https://creativecommons.org/licenses/by-nc/4.0) which permits unrestricted noncommercial use, distribution, and reproduction in any medium, provided the original work is properly cited. |
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| Snippet | Gastrointestinal stromal tumors (GISTs) frequently harbor activating gene mutations in either
or platelet-derived growth factor receptor A (
) and are highly... Gastrointestinal stromal tumors (GISTs) frequently harbor activating gene mutations in either KIT or platelet-derived growth factor receptor A (PDGFRA) and are... Purpose: Gastrointestinal stromal tumors (GISTs) frequently harbor activating gene mutations in either KIT or platelet-derived growth factor receptor A... |
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| Title | Genetic Characterization of Molecular Targets in Korean Patients with Gastrointestinal Stromal Tumors |
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