Cho Songde, Kitadai Yasuhiko, Yoshida Shigeto, Tanaka Shinji, Yoshihara Masaharu, Yoshida Kazuhiro, Chayama Kazuaki
Department of Medicine and Molecular Science, Hiroshima University Graduate School of Biomedical Sciences, Minami-ku, Hiroshima 734-8551, Japan.
Int J Oncol. 2006 Jun;28(6):1361-7.
The goal of this study was to investigate the association of mutations in the KIT gene and the platelet-derived growth factor receptor alpha (PDGFRA) gene with clinicopathological features of patients with gastrointestinal stromal tumor (GIST) localized in the stomach. We evaluated 56 gastric GISTs for KIT and PDGFRA mutations. DNA was extracted from paraffin-embedded tumor specimens, and exons 9, 11, 13 and 17 of the KIT gene and exons 12 and 18 of the PDGFRA gene were amplified by polymerase chain reaction and sequenced. The genetic features were then compared with the clinicopathological features. Immunohistochemistry was performed for KIT, CD34, Ki-67 (as a marker of cell proliferation) and CD31 (as a marker of microvessel density), and apoptosis was assessed by in situ DNA nick-end labeling. Thirty-four (61%) of the 56 GISTs had a mutation in exon 11 of KIT, and 2 (4%) had a mutation in exon 13 of KIT. Deletions in exon 11 of KIT were the most common mutation encountered in the present study. No mutations were found in exon 9 or 17 of KIT. Six of the 20 GISTs lacking KIT mutations had a mutation in exon 18 of PDGFRA, and 1 had a mutation in exon 12 of PDGFRA. The KIT mutation-positive GISTs showed more frequent liver metastases and higher mortality than KIT mutation-negative GISTs. Our data indicate that KIT mutations, especially deletions in exon 11, are markers of poor prognosis for gastric GISTs.
本研究的目的是调查KIT基因和血小板衍生生长因子受体α（PDGFRA）基因的突变与胃原发性胃肠道间质瘤（GIST）患者临床病理特征之间的关联。我们评估了56例胃GIST中的KIT和PDGFRA突变情况。从石蜡包埋的肿瘤标本中提取DNA，通过聚合酶链反应扩增KIT基因的第9、11、13和17外显子以及PDGFRA基因的第12和18外显子，并进行测序。然后将基因特征与临床病理特征进行比较。对KIT、CD34、Ki-67（作为细胞增殖标志物）和CD31（作为微血管密度标志物）进行免疫组织化学检测，并通过原位DNA缺口末端标记评估细胞凋亡。56例GIST中，34例（61%）KIT基因第11外显子发生突变，2例（4%）KIT基因第13外显子发生突变。KIT基因第11外显子缺失是本研究中最常见的突变类型。未发现KIT基因第9或17外显子有突变。20例无KIT基因突变的GIST中，6例PDGFRA基因第18外显子发生突变，1例PDGFRA基因第12外显子发生突变。与KIT基因突变阴性的GIST相比，KIT基因突变阳性的GIST肝转移更频繁，死亡率更高。我们的数据表明，KIT基因突变，尤其是第11外显子缺失，是胃GIST预后不良的标志物。
