Genetic and epigenetic analysis of the KLF4 gene in gastric cancer
Genetic and epigenetic analysis of the KLF4 gene in gastric cancer
复制标题
DOI：
10.1111/j.1600-0463.2007.apm_643.x
复制
发表时间：
2007-07-01
期刊：
影响因子：
2.8
通讯作者：
Park, Won Sang
中科院分区：
文献类型：
--
作者：
Cho, Yong Gu;Song, Jae Hwi;Park, Won Sang
KLF 4是一种肠道富集的Kruppel样因子，在胃肠道上皮细胞的增殖和分化过程中发挥重要作用。在人类肿瘤中观察到KLF 4表达的缺失，特别是在胃肠道中。本研究通过对47例胃腺瘤和81例胃腺癌中KLF 4基因的体细胞突变、D9 S53和D9 S105两个微卫星标记的等位基因丢失以及高甲基化进行分析，探讨了胃癌中KLF 4基因失活的分子基础。突变分析显示，在弥漫型进展期胃腺癌中有一个KLF 4基因突变，但在胃腺瘤中没有。该突变为外显子3第107位密码子GGG -> AGG（Gly -> Arg）的体细胞错义突变，编码该蛋白的转录激活结构域。在31例信息性胃腺瘤病例中的7例（22.6%）和48例信息性癌症病例中的15例（31.3%）中发现一个或两个标记物的等位基因丢失。此外，仅在两种胃癌中观察到KLF 4基因启动子高甲基化。这些结果表明，KLF 4基因的遗传和表观遗传改变可能在胃癌发生中起次要作用。
KLF4, which is also known as the gut-enriched Kruppel-like factor, plays important roles during the proliferation and differentiation of gastrointestinal epithelial cells. A loss of KLF4 expression has been observed in human tumors, particularly in the gastrointestinal tract. In this study, the molecular basis of the KLF4 inactivation in gastric cancer was investigated by analyzing the somatic mutation, the allelic loss with two microsatellite markers, D9S53 and D9S105, and hypermethylation of the KLF4 gene in 47 gastric adenomas and 81 gastric adenocarcinomas. Mutational analysis revealed one mutation of the KLF4 gene in a diffuse-type advanced gastric adenocarcinoma, but not in the gastric adenoma. This mutation was a somatic missense mutation, GGG -> AGG (Gly -> Arg) at codon 107 in exon 3, which encodes a transcriptional activation domain of the protein. An allelic loss was found in 7 (22.6%) of the 31 informative gastric adenoma cases and 15 (31.3%) of the 48 informative cancer cases at one or both markers. In addition, promoter hypermethylation of the KLF4 gene was observed in only two gastric cancers. These results suggest that genetic and epigenetic alterations of the KLF4 gene might play a minor role in gastric carcinogenesis.