title: Analysis of mutation of the c-Kit gene andPDGFRAin gastrointestinal stromal tumors.
abstract: The aim of the present study was to investigate mutation status of thec-Kit gene (KIT)andPDGFRAin patients with a gastrointestinal stromal tumor (GIST). In total, 93 patients with a GIST were included in the study, in which polymerase chain reaction amplification and gene sequencing were used to detect the sequences of exons 9, 11, 13 and 17 inKITand exons 12 and 18 inPDGFRA.KITmutations were detected in 64 cases (68.82%), of which exon 11 mutations were detected in 56 cases (60.22%), exon 13 mutations were detected in three cases (3.23%) and one case (1.08%) was shown to have a mutation in exon 17. The most common mutation in exon 11 was a deletion, which accounted for 55.36% (31/56) of the cases, followed by a point mutation observed in 26.79% (15/56) of the cases, while an insertion (tandem repeats) was identified in 14.29% (8/56) of the cases, and 3.57% (2/56) of the exon 11 mutations were deletions associated with a point mutation. The majority of the mutations were heterozygous, with only a few homozygous mutations. Mutational analysis revealed the mutations to be more concentrated in the classic hot zone at the 5'-end, followed by the tandem repeat frame at the 3'-end. In four cases, a mutation was detected in exon 18 ofPDGFRA, of which one was associated with a mutation inKIT. The remaining three cases (10.34%, 3/29) were not associated with mutations inKITand accounted for 37.5% (3/8) of the CD117-negative GIST cases. Therefore, the majority of the GIST cases were characterized by mutations inKITorPDGFRA, which were directly associated with the disease. Pairs of different mutations in the same exon ofKIT, orKITmutations coupled with pairs of mutations inPDGFRA, were detected in a small number of patients. Imatinib is a small molecule tyrosine kinase inhibitor and is the first line targeted treatment for GIST, resulting in markedly improved survival rates. Thus, gene mutation genotyping may provide inspiration and guidance for imatinib-based targeted cancer therapy.
authors.affiliation: Department of Pathology, The General Military Hospital of Beijing PLA, Beijing 100700, P.R. China.
authors.forename: Chun-Wei
authors.initials: CW
authors.lastname: Xu
authors.affiliation: Department of Oncology, Affiliated Zhongshan Hospital of Dalian University, Dalian, Liaoning 116001, P.R. China.
authors.forename: Shan
authors.initials: S
authors.lastname: Lin
authors.affiliation: Department of Oncology, The Second Affiliated Hospital of Baotou Medical College, Baotou, Inner Mongolia 014030, P.R. China.
authors.forename: Wu-Long
authors.initials: WL
authors.lastname: Wang
authors.affiliation: Department of Oncology, Affiliated Zhongshan Hospital of Dalian University, Dalian, Liaoning 116001, P.R. China.
authors.forename: Wen-Bin
authors.initials: WB
authors.lastname: Gao
authors.affiliation: Department of Oncology, Affiliated Zhongshan Hospital of Dalian University, Dalian, Liaoning 116001, P.R. China.
authors.forename: Jin-Yan
authors.initials: JY
authors.lastname: Lv
authors.affiliation: Department of Clinical Medicine, Dalian Medical University, Dalian, Liaoning 116044, P.R. China.
authors.forename: Jing-Shan
authors.initials: JS
authors.lastname: Gao
authors.affiliation: Department of Pathology, The General Military Hospital of Beijing PLA, Beijing 100700, P.R. China.
authors.forename: Li-Ying
authors.initials: LY
authors.lastname: Zhang
authors.affiliation: Department of Oncology, The General Military Hospital of Beijing PLA, Beijing 100700, P.R. China.
authors.forename: Yang
authors.initials: Y
authors.lastname: Li
authors.affiliation: Department of Pathology, Shanxi Da Hospital, Shanxi Academy of Medical Sciences, Taiyuan, Shanxi 030001, P.R. China.
authors.forename: Lin
authors.initials: L
authors.lastname: Wang
authors.affiliation: Department of Pathology, The People's Hospital of Weifang, Weifang, Shandong 261041, P.R. China.
authors.forename: Yu-Ping
authors.initials: YP
authors.lastname: Zhang
authors.affiliation: Department of Pathology, The General Military Hospital of Beijing PLA, Beijing 100700, P.R. China.
authors.forename: Yu-Wang
authors.initials: YW
authors.lastname: Tian
keywords: PDGFRA; c-Kit; gastrointestinal stromal tumors; gene mutation; molecular detection