Cho Yong Gu, Kim Chang Jae, Park Cho Hyun, Yang Young Mok, Kim Su Young, Nam Suk Woo, Lee Sug Hyung, Yoo Nam Jin, Lee Jung Young, Park Won Sang
Department of Pathology, College of Medicine, The Catholic University of Korea, 505 Banpo-dong, Seocho-gu, Seoul 137-701, Korea.
Oncogene. 2005 Jun 30;24(28):4588-90. doi: 10.1038/sj.onc.1208670.
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.
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，并广泛参与分化与发育、生长相关信号转导、细胞增殖、凋亡及血管生成过程。为确定KLF6基因的遗传改变是否参与胃癌的发生和/或进展，我们对80例散发型胃癌进行了筛查，以检测KLF6基因的突变和等位基因缺失情况。在KLF6基因的反式激活域检测到4个错义突变，即S155R、P172T、S180L和R198K，其中1例为双等位基因突变，一个等位基因发生体细胞突变，另一个等位基因缺失。所有发生突变的病例均为伴有淋巴结转移的进展期肠型胃癌。此外，在37例信息充分的病例中，有16例（43.2%）在KLF6位点显示等位基因缺失。有趣的是，等位基因缺失在肠型胃癌中也很常见。因此，我们的数据表明，KLF6基因的遗传改变可能在散发型胃癌的发生或进展中起重要作用。
