Genetic alterations of the KLF6 gene in gastric cancer
Genetic alterations of the KLF6 gene in gastric cancer
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DOI：
10.1038/sj.onc.1208670
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发表时间：
2005-06-30
期刊：
影响因子：
8
通讯作者：
Park, WS
中科院分区：
文献类型：
--
作者：
Cho, YG;Kim, CJ;Park, WS
KLF6是一种锌指肿瘤抑制因子，在多种人类癌症中经常发生突变，广泛参与分化发育、生长相关信号转导、细胞增殖、细胞凋亡和血管生成。为了确定KLF6基因的遗传改变是否与胃癌的发生和/或进展有关，我们对80例散发性胃癌患者进行了KLF6基因突变和等位基因丢失的筛查。KLF6基因反激活域检测到S155R、P172 T、S180L和R198 K 4个错义突变，其中1个为双等位基因突变，1个等位基因体细胞突变，其余等位基因缺失。所有发生突变的病例均为晚期肠型胃癌伴淋巴结转移。此外，在37例信息丰富的病例中，有16例（43.2%）在KLF6位点出现等位基因缺失。有趣的是，等位基因丢失在肠型胃癌中也很常见。因此，我们的数据提示KLF6基因的遗传改变可能在散发性胃癌的发生或进展中起重要作用。
The KLF6 is a zinc-finger tumor suppressor that is frequently mutated in several human cancers and broadly involved in differentiation and development, growth-related signal transduction, cell proliferation, apoptosis, and angiogenesis. To determine whether genetic alterations of KLF6 gene are involved in the development and/or progression of gastric cancer, we have screened a set of 80 sporadic gastric cancers for mutations and allele loss of the KLF6 gene. Four missense mutations, S155R, P172 T, S180L, and R198 K, were detected in transactivation domain of the KLF6 gene and one of them had biallelic mutations with somatic mutation of one allele and loss of the remaining allele. All of the cases with mutation were of advanced intestinal-type gastric cancer with lymph node metastasis. In addition, 16 (43.2%) of 37 informative cases showed allelic loss at KLF6 locus. Interestingly, allelic loss was also frequent in intestinal-type gastric cancer. Therefore, our data suggest that genetic alterations of KLF6 gene might play an important role in the development or progression of sporadic gastric cancers.