Nomoto S, Kinoshita T, Mori T, Kato K, Sugimoto H, Kanazumi N, Takeda S, Nakao A
Department of Surgery II, Graduate School & Faculty of Medicine, University of Nagoya, Nagoya, Japan.
Br J Cancer. 2008 May 20;98(10):1690-5. doi: 10.1038/sj.bjc.6604333. Epub 2008 May 13.
Alteration in transforming growth factor-beta signalling pathway is one of the main causes of pancreatic cancer. The human runt-related transcription factor 3 gene (RUNX3) is an important component of this pathway. RUNX3 locus 1p36 is commonly deleted in a variety of human cancers, including pancreatic cancer. Therefore, we examined genetic and epigenetic alterations of RUNX3 in human pancreatic cancer. Thirty-two patients with pancreatic cancer were investigated in this study. We examined the methylation status of RUNX3 promoter region, loss of heterozygosity (LOH) at 1p36, and conducted a mutation analysis. The results were compared with clinicopathological data. Promoter hypermethylation was detected in 20 (62.5%) of 32 pancreatic cancer tissues, confirmed by sequence of bisulphite-treated DNA. Loss of heterozygosity was detected in 11 (34.3%) of 32 pancreatic cancers. In comparison with clinicopathological data, hypermethylation showed a relation with a worse prognosis (P=0.0143). Hypermethylation and LOH appear to be common mechanisms for inactivation of RUNX3 in pancreatic cancer. Therefore, RUNX3 may be an important tumour suppressor gene related to pancreatic cancer.
转化生长因子-β信号通路的改变是胰腺癌的主要病因之一。人类 runt 相关转录因子 3 基因（RUNX3）是该信号通路的一个重要组成部分。RUNX3 基因座 1p36 在包括胰腺癌在内的多种人类癌症中常发生缺失。因此，我们研究了人类胰腺癌中 RUNX3 的基因和表观遗传改变。本研究纳入了 32 例胰腺癌患者。我们检测了 RUNX3 启动子区域的甲基化状态、1p36 处的杂合性缺失（LOH），并进行了突变分析。将结果与临床病理数据进行比较。在 32 例胰腺癌组织中的 20 例（62.5%）检测到启动子高甲基化，经亚硫酸氢盐处理的 DNA 测序证实。在 32 例胰腺癌中的 11 例（34.3%）检测到杂合性缺失。与临床病理数据相比，高甲基化与预后较差相关（P = 0.0143）。高甲基化和 LOH 似乎是胰腺癌中 RUNX3 失活的常见机制。因此，RUNX3 可能是与胰腺癌相关的一个重要肿瘤抑制基因。
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