Kondo S, Shinomura Y, Miyazaki Y, Kiyohara T, Tsutsui S, Kitamura S, Nagasawa Y, Nakahara M, Kanayama S, Matsuzawa Y
Department of Internal Medicine and Molecular Science, Graduate School of Medicine, Osaka University, Japan.
Cancer Res. 2000 Aug 15;60(16):4328-30.
The Bcl-2 homologue Bak is a potent inducer of apoptosis. We performed PCR-based single-strand conformational polymorphism and sequencing analysis of the entire coding region of the bak gene (exons 2-6) in 24 primary gastric cancers (6 early-stage and 18 advanced-stage cancers) and 20 primary colorectal cancers (6 early-stage and 14 advanced-stage cancers). The data herein demonstrate, for the first time, the mutation of the bak gene in gastric and colorectal cancers. Missense bak gene mutations were observed in 3 of 24 (12.5%) gastric cancers and 2 of 20 (10.0%) colorectal cancers. Sequence alterations without amino acid alteration were observed 1 of 24 (4.2%) gastric cancers and 2 of 20 (10.0%) colorectal cancers. Mutations in the bak gene were observed only in advanced-stage gastrointestinal cancers but not in early-stage cancers. Our observations suggest that mutations in this gene predispose bearers to the development of gastrointestinal malignancies in at least a subset of the cases.
Bcl-2同源物Bak是一种有效的凋亡诱导剂。我们对24例原发性胃癌（6例早期癌和18例进展期癌）和20例原发性结直肠癌（6例早期癌和14例进展期癌）的bak基因整个编码区（外显子2 - 6）进行了基于聚合酶链反应的单链构象多态性及测序分析。本文数据首次证实了胃癌和结直肠癌中bak基因的突变。在24例胃癌中有3例（12.5%）、20例结直肠癌中有2例（10.0%）观察到错义bak基因突变。在24例胃癌中有1例（4.2%）、20例结直肠癌中有2例（10.0%）观察到无氨基酸改变的序列改变。bak基因突变仅在进展期胃肠道癌中观察到，而在早期癌中未观察到。我们的观察结果表明，至少在部分病例中，该基因突变使携带者易患胃肠道恶性肿瘤。
