He Hui-ying, Fang Wei-gang, Zhong Hao-hao, Li Yan, Zheng Jie, Du Juan, Heng Wan-jie, Wu Bing-quan
Department of Pathology, Health Science Center, Peking University, Beijing 100083, China.
Zhonghua Bing Li Xue Za Zhi. 2006 May;35(5):262-6.
To investigate the status of c-kit and PDGFRA mutations of GIST in a the large sample of Chinese patients.
One hundred and sixty-five cases were evaluated for the presence of c-kit and PDGFRA mutations. Exon 9, 11, 13, 17 of c-kit and exon 12, 18 of PDGFRA were analyzed by PCR amplification and direct sequencing.
Immunohistochemical demonstrations of KIT (CD117) were seen in 94% of the cases (155/165). Overall, c-kit mutations were identified in 76.1% (118/155) of CD117 positive cases: 67.1% (104/155) involving exon 11, 7.1% (11/155) involving exon 9, 1.3% (2/155) involving exon 13 and 0.6% (1/155) involving exon 17. The c-kit exon 11 mutations were mostly heterogeneous and clustered in the classic "hot spot" at the 5' end of the exon, including in-frame deletion and point mutation. The second "hot spots" were internal tandem duplications (ITD) at the 3' end of the exon, which were associated with female patient, older age, stomach location and low mitotic counts. The exon 9 mutations correlated with a distinct subset of GISTs involving the small bowel of young male patients. A new point mutation of L641P was identified in exon 13. PDGFRA mutations were present in 50% (5/10) of CD117-negative GISTs, all involving exon 18 with the majority of mutations being D842V. One novel in-frame deletion of IMHD mutation at codon 843 - 846 with S847T was identified. GISTs with PDGFRA mutations were often larger tumors arising from the omentum/mesentery of young male patients with high risk of aggressive behavior.
The vast majority of GISTs in this study harbored c-kit and PDGFRA mutations, there were non-random relations between the gene mutation patterns and the locations of GISTs. It appears that Chinese GIST patients have some unique mutation patterns. It is necessary to evaluate the gene mutations status of GISTs to guide target therapy.
在大量中国患者样本中研究胃肠道间质瘤（GIST）的c-kit和血小板衍生生长因子受体α（PDGFRA）突变情况。
对165例患者评估c-kit和PDGFRA突变情况。通过聚合酶链反应（PCR）扩增和直接测序分析c-kit的第9、11、13、17外显子以及PDGFRA的第12、18外显子。
94%（155/165）的病例KIT（CD117）免疫组化呈阳性。总体而言，在76.1%（118/155）的CD117阳性病例中检测到c-kit突变：67.1%（104/155）涉及第11外显子，7.1%（11/155）涉及第9外显子，1.3%（2/155）涉及第13外显子，0.6%（1/155）涉及第17外显子。c-kit第11外显子突变大多为异质性，集中在外显子5'端的经典“热点”区域，包括框内缺失和点突变。第二个“热点”是外显子3'端的内部串联重复（ITD），与女性患者、年龄较大、胃部位以及低核分裂象有关。第9外显子突变与涉及年轻男性患者小肠的特定GIST亚组相关。在第13外显子中发现了一个新的L641P点突变。在50%（5/10）的CD117阴性GIST中检测到PDGFRA突变，均涉及第18外显子，大多数突变为D842V。还发现了一个新的密码子843 - 846的框内缺失IMHD突变，伴有S847T。具有PDGFRA突变的GIST通常是起源于年轻男性患者大网膜/肠系膜的较大肿瘤，具有侵袭性行为的高风险。
本研究中绝大多数GIST存在c-kit和PDGFRA突变，基因突变模式与GIST的位置之间存在非随机关系。中国GIST患者似乎有一些独特的突变模式。评估GIST的基因突变状态以指导靶向治疗很有必要。
