Correlation of imatinib resistance with the mutational status of KIT and PDGFRA genes in gastrointestinal stromal tumors

A meta-analysis

Research output: Contribution to journalArticle

40 Citations (Scopus)

Abstract

Background & Aims: Imatinib resistance is the most important clinical issue in patients with gastrointestinal stromal tumor (GIST). However, the association of imatinib resistance with the genetic characteristics of GIST has not been clearly defined. Our meta-analysis aimed to investigate the association between imatinib resistance and KIT and PDGFRA mutations in GIST. Methods. We identified all relevant studies in PubMed and Embase. The effect sizes were calculated as prevalence or odds ratio (OR) with a random-effects model. Results. We identified 10 eligible studies that included 1083 GIST cases. Total imatinib resistance was found in 35.5 % of PDGFRA-mutant tumors (OR = 2.9, P = 0.038), 33.7% of wild-type tumors (KIT and PDGFRA non-mutant tumors; OR = 2.8, P = 0.002), and 27.4% of KIT-mutant tumors (OR = 0.3, P = 0.001). Primary imatinib resistance was found in 50.0% of PDGFRA-mutant tumors (OR = 10.9, P = 0.031), 33.4% of wild-type tumors (OR = 5.9, P = 0.060), and 8.9% of KIT-mutant tumors (OR = 0.2, P = 0.025). KIT exon 9-mutant tumors showed primary resistance more frequently than exon 11-mutant and other tumors (OR = 7.6, P < 0.001). Regarding secondary resistance associated with KIT second-site mutations, the exon 17 mutation (54.5%) was most frequent, followed by exon 13 (38.3%) and 14 (13.4%) mutations. Conclusion. Our meta-analysis indicates that imatinib resistance is closely associated with KIT and PDGFRA genotypes in GIST. Thus, the mutational status of KIT and PDGFRA might predict response to imatinib in GIST patients.

Original languageEnglish
Pages (from-to)413-418
Number of pages6
JournalJournal of Gastrointestinal and Liver Diseases
Volume22
Issue number4
Publication statusPublished - 2013 Dec 1

Fingerprint

Gastrointestinal Stromal Tumors
Meta-Analysis
Odds Ratio
Genes
Neoplasms
Exons
Mutation
Imatinib Mesylate
PubMed
Genotype

Keywords

  • Gastrointestinal stromal tumor
  • Imatinib
  • Resistance

ASJC Scopus subject areas

  • Gastroenterology

Cite this

@article{41b3bf0f88c842c5ab9cdcf8fac37602,
title = "Correlation of imatinib resistance with the mutational status of KIT and PDGFRA genes in gastrointestinal stromal tumors: A meta-analysis",
abstract = "Background & Aims: Imatinib resistance is the most important clinical issue in patients with gastrointestinal stromal tumor (GIST). However, the association of imatinib resistance with the genetic characteristics of GIST has not been clearly defined. Our meta-analysis aimed to investigate the association between imatinib resistance and KIT and PDGFRA mutations in GIST. Methods. We identified all relevant studies in PubMed and Embase. The effect sizes were calculated as prevalence or odds ratio (OR) with a random-effects model. Results. We identified 10 eligible studies that included 1083 GIST cases. Total imatinib resistance was found in 35.5 {\%} of PDGFRA-mutant tumors (OR = 2.9, P = 0.038), 33.7{\%} of wild-type tumors (KIT and PDGFRA non-mutant tumors; OR = 2.8, P = 0.002), and 27.4{\%} of KIT-mutant tumors (OR = 0.3, P = 0.001). Primary imatinib resistance was found in 50.0{\%} of PDGFRA-mutant tumors (OR = 10.9, P = 0.031), 33.4{\%} of wild-type tumors (OR = 5.9, P = 0.060), and 8.9{\%} of KIT-mutant tumors (OR = 0.2, P = 0.025). KIT exon 9-mutant tumors showed primary resistance more frequently than exon 11-mutant and other tumors (OR = 7.6, P < 0.001). Regarding secondary resistance associated with KIT second-site mutations, the exon 17 mutation (54.5{\%}) was most frequent, followed by exon 13 (38.3{\%}) and 14 (13.4{\%}) mutations. Conclusion. Our meta-analysis indicates that imatinib resistance is closely associated with KIT and PDGFRA genotypes in GIST. Thus, the mutational status of KIT and PDGFRA might predict response to imatinib in GIST patients.",
keywords = "Gastrointestinal stromal tumor, Imatinib, Resistance",
author = "Ju-Han Lee and Younghye Kim and Jung-Woo Choi and Kim, {Young Sik}",
year = "2013",
month = "12",
day = "1",
language = "English",
volume = "22",
pages = "413--418",
journal = "Journal of Gastrointestinal and Liver Diseases",
issn = "1841-8724",
publisher = "Romanian Society of Gastroenterology",
number = "4",

}

TY - JOUR

T1 - Correlation of imatinib resistance with the mutational status of KIT and PDGFRA genes in gastrointestinal stromal tumors

T2 - A meta-analysis

AU - Lee, Ju-Han

AU - Kim, Younghye

AU - Choi, Jung-Woo

AU - Kim, Young Sik

PY - 2013/12/1

Y1 - 2013/12/1

N2 - Background & Aims: Imatinib resistance is the most important clinical issue in patients with gastrointestinal stromal tumor (GIST). However, the association of imatinib resistance with the genetic characteristics of GIST has not been clearly defined. Our meta-analysis aimed to investigate the association between imatinib resistance and KIT and PDGFRA mutations in GIST. Methods. We identified all relevant studies in PubMed and Embase. The effect sizes were calculated as prevalence or odds ratio (OR) with a random-effects model. Results. We identified 10 eligible studies that included 1083 GIST cases. Total imatinib resistance was found in 35.5 % of PDGFRA-mutant tumors (OR = 2.9, P = 0.038), 33.7% of wild-type tumors (KIT and PDGFRA non-mutant tumors; OR = 2.8, P = 0.002), and 27.4% of KIT-mutant tumors (OR = 0.3, P = 0.001). Primary imatinib resistance was found in 50.0% of PDGFRA-mutant tumors (OR = 10.9, P = 0.031), 33.4% of wild-type tumors (OR = 5.9, P = 0.060), and 8.9% of KIT-mutant tumors (OR = 0.2, P = 0.025). KIT exon 9-mutant tumors showed primary resistance more frequently than exon 11-mutant and other tumors (OR = 7.6, P < 0.001). Regarding secondary resistance associated with KIT second-site mutations, the exon 17 mutation (54.5%) was most frequent, followed by exon 13 (38.3%) and 14 (13.4%) mutations. Conclusion. Our meta-analysis indicates that imatinib resistance is closely associated with KIT and PDGFRA genotypes in GIST. Thus, the mutational status of KIT and PDGFRA might predict response to imatinib in GIST patients.

AB - Background & Aims: Imatinib resistance is the most important clinical issue in patients with gastrointestinal stromal tumor (GIST). However, the association of imatinib resistance with the genetic characteristics of GIST has not been clearly defined. Our meta-analysis aimed to investigate the association between imatinib resistance and KIT and PDGFRA mutations in GIST. Methods. We identified all relevant studies in PubMed and Embase. The effect sizes were calculated as prevalence or odds ratio (OR) with a random-effects model. Results. We identified 10 eligible studies that included 1083 GIST cases. Total imatinib resistance was found in 35.5 % of PDGFRA-mutant tumors (OR = 2.9, P = 0.038), 33.7% of wild-type tumors (KIT and PDGFRA non-mutant tumors; OR = 2.8, P = 0.002), and 27.4% of KIT-mutant tumors (OR = 0.3, P = 0.001). Primary imatinib resistance was found in 50.0% of PDGFRA-mutant tumors (OR = 10.9, P = 0.031), 33.4% of wild-type tumors (OR = 5.9, P = 0.060), and 8.9% of KIT-mutant tumors (OR = 0.2, P = 0.025). KIT exon 9-mutant tumors showed primary resistance more frequently than exon 11-mutant and other tumors (OR = 7.6, P < 0.001). Regarding secondary resistance associated with KIT second-site mutations, the exon 17 mutation (54.5%) was most frequent, followed by exon 13 (38.3%) and 14 (13.4%) mutations. Conclusion. Our meta-analysis indicates that imatinib resistance is closely associated with KIT and PDGFRA genotypes in GIST. Thus, the mutational status of KIT and PDGFRA might predict response to imatinib in GIST patients.

KW - Gastrointestinal stromal tumor

KW - Imatinib

KW - Resistance

UR - http://www.scopus.com/inward/record.url?scp=84890482641&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84890482641&partnerID=8YFLogxK

M3 - Article

VL - 22

SP - 413

EP - 418

JO - Journal of Gastrointestinal and Liver Diseases

JF - Journal of Gastrointestinal and Liver Diseases

SN - 1841-8724

IS - 4

ER -