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Ma YY, Yu S, He XJ, et al. Involvement of c-KIT mutation in the development of gastrointestinal stromal tumors through proliferation promotion and apoptosis inhibition. Onco Targets Ther. 2014;7:637-43doi: 10.2147/OTT.S60458.
Ma, Y. Y., Yu, S., He, X. J., Xu, Y., Wu, F., Xia, Y. J., Guo, K., Wang, H. J., Ye, Z. Y., Zhang, W., & Tao, H. Q. (2014). Involvement of c-KIT mutation in the development of gastrointestinal stromal tumors through proliferation promotion and apoptosis inhibition. OncoTargets and therapy, 7637-43. https://doi.org/10.2147/OTT.S60458
Ma, Ying-Yu, et al. "Involvement of c-KIT mutation in the development of gastrointestinal stromal tumors through proliferation promotion and apoptosis inhibition." OncoTargets and therapy vol. 7 (2014): 637-43. doi: https://doi.org/10.2147/OTT.S60458
Ma YY, Yu S, He XJ, Xu Y, Wu F, Xia YJ, Guo K, Wang HJ, Ye ZY, Zhang W, Tao HQ. Involvement of c-KIT mutation in the development of gastrointestinal stromal tumors through proliferation promotion and apoptosis inhibition. Onco Targets Ther. 2014 May 02;7:637-43. doi: 10.2147/OTT.S60458. eCollection 2014. PMID: 24833907; PMCID: PMC4014364.
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Onco Targets Ther. 2014 May 02;7:637-43. doi: 10.2147/OTT.S60458. eCollection 2014.

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

OncoTargets and therapy

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

Affiliations

  1. Key Laboratory of Gastroenterology of Zhejiang Province, Zhejiang Provincial People's Hospital, Hangzhou, People's Republic of China.
  2. Wenzhou Medical College, Wenzhou, Zhejiang, People's Republic of China.
  3. Key Laboratory of Gastroenterology of Zhejiang Province, Zhejiang Provincial People's Hospital, Hangzhou, People's Republic of China ; Department of Gastrointestinal Surgery, Zhejiang Provincial People's Hospital, Hangzhou, People's Republic of China.
  4. Department of Gastrointestinal Surgery, Zhejiang Provincial People's Hospital, Hangzhou, People's Republic of China.

PMID: 24833907 PMCID: PMC4014364 DOI: 10.2147/OTT.S60458

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: apoptosis; c-KIT; gastrointestinal stromal tumors; mutation; proliferation

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