Back to Journals » OncoTargets and Therapy » Volume 7

Involvement of c-KIT mutation in the development of gastrointestinal stromal tumors through proliferation promotion and apoptosis inhibition

Authors Ma Y, Yu S, He X, Xu Y, Wu F, Xia Y, Guo K, Wang H, Ye Z, Zhang W, Tao H

Received 10 January 2014

Accepted for publication 26 February 2014

Published 2 May 2014 Volume 2014:7 Pages 637—643


Checked for plagiarism Yes

Review by Single-blind

Peer reviewer comments 3

Ying-Yu Ma,1 Sheng Yu,2 Xu-Jun He,1 Yuan Xu,2 Fang Wu,2 Ying-Jie Xia,1 Kun Guo,2 Hui-Ju Wang,1 Zai-Yuan Ye,1,3 Wei Zhang,3 Hou-Quan Tao1,3

Key Laboratory of Gastroenterology of Zhejiang Province, Zhejiang Provincial People’s Hospital, Hangzhou, 2Wenzhou Medical College, Wenzhou, Zhejiang, 3Department of Gastrointestinal Surgery, Zhejiang Provincial People’s Hospital, Hangzhou, People’s Republic of China

Abstract: The aim of this study was to discuss the role of c-KIT mutation in the pathogenesis of gastrointestinal stromal tumors (GISTs) and analyze its correlation with proliferation and apoptosis. c-KIT and PDGFRA genotypes were examined by deoxyribonucleic acid sequencing. Immunohistochemistry was performed to determine the expression levels of Kit, Ki-67 (proliferation marker), and apoptotic protease-activating factor (APAF)-1 (apoptosis marker) and the relationship between their three genes. In the 68 cases examined, 44 cases (64.7%) showed mutations in one of the four exons of c-KIT. The mutations were most frequently found in exon 11 (30 cases [44.1%]), followed by exon 9 (ten cases [14.7%]) and exon 13 (four cases [5.9%]). c-KIT mutation showed no association with prognostic factors using the classification of risk of aggressive behavior in GIST proposed by Fletcher et al. No cases had mutated exon 17 of c-KIT, and neither did exon 12, 14, or 18 of PDGFRA in our present study. There was a positive correlation between the expression level of Kit and Ki-67 (R=0.282, P=0.020). Conversely, a negative correlation was found between the expression levels of Kit and APAF1 (R=−0.243, P=0.046). In conclusion, most GISTs with Kit expression showed c-KIT mutation. Kit expression has a positive correlation with Ki-67 and a negative correlation with APAF1, showing that c-KIT is involved in GIST occurrence and development through proliferation promotion and apoptosis inhibition.

Keywords: gastrointestinal stromal tumors, c-KIT, mutation, proliferation, apoptosis

Creative Commons License This work is published and licensed by Dove Medical Press Limited. The full terms of this license are available at and incorporate the Creative Commons Attribution - Non Commercial (unported, v3.0) License. By accessing the work you hereby accept the Terms. Non-commercial uses of the work are permitted without any further permission from Dove Medical Press Limited, provided the work is properly attributed. For permission for commercial use of this work, please see paragraphs 4.2 and 5 of our Terms.

Download Article [PDF]  View Full Text [HTML][Machine readable]