遗传性非息肉病性结直肠癌患者腺瘤中的β-连环蛋白和腺瘤性息肉病 coli（APC）突变。

Beta-catenin and adenomatous polyposis coli (APC) mutations in adenomas from hereditary non-polyposis colorectal cancer patients.

作者信息

Akiyama Y, Nagasaki H, Yagi K O, Nomizu T, Yuasa Y

机构信息

Department of Hygiene and Oncology, Tokyo Medical and Dental University School of Medicine, 1-5-45 Yushima, Bunkyo-ku, 113-8519, Tokyo, Japan.

出版信息

Cancer Lett. 2000 Sep 1;157(2):185-91. doi: 10.1016/s0304-3835(00)00486-9.

DOI:10.1016/s0304-3835(00)00486-9

PMID:10936679

Abstract

To clarify the roles of the adenomatous polyposis coli (APC) and beta-catenin genes in hereditary nonpolyposis colorectal cancer (HNPCC) tumorigenesis, we searched for their mutations in 14 HNPCC adenomas with microsatellite instability (MSI). Seven (50%) adenomas exhibited somatic APC mutations, five of which were frameshift mutations and the other two nonsense ones. However, the APC mutational spectrum of these adenomas was similar to that of sporadic colorectal tumors. Two adenomas (14.3%) with undetectable APC alterations showed missense mutations at codon 45 (TCT to TTT or to CCT) in beta-catenin. The MSI frequency in adenomas with beta-catenin mutations was significantly higher than that with APCones (P<0.001), indicating that mutations of beta-catenin rather than APC are strongly associated with MSI. These data suggest that adenomas with beta-catenin activating mutations and some with APC inactivating mutations may be precursors of HNPCC colorectal cancers.

摘要

为了阐明腺瘤性息肉病 coli（APC）和β-连环蛋白基因在遗传性非息肉病性结直肠癌（HNPCC）肿瘤发生中的作用，我们在 14 个具有微卫星不稳定性（MSI）的 HNPCC 腺瘤中寻找它们的突变。7 个（50%）腺瘤出现体细胞 APC 突变，其中 5 个是移码突变，另外 2 个是无义突变。然而，这些腺瘤的 APC 突变谱与散发性结直肠肿瘤的相似。2 个（14.3%）未检测到 APC 改变的腺瘤在β-连环蛋白的第 45 密码子处出现错义突变（TCT 变为 TTT 或 CCT）。β-连环蛋白突变的腺瘤中的 MSI 频率显著高于 APC 无突变的腺瘤（P<0.001），表明β-连环蛋白而非 APC 的突变与 MSI 密切相关。这些数据表明，具有β-连环蛋白激活突变的腺瘤和一些具有 APC 失活突变的腺瘤可能是 HNPCC 结直肠癌的前体。