β-Catenin and adenomatous polyposis coli (APC) mutations in adenomas from hereditary non-polyposis colorectal cancer patients
β-Catenin and adenomatous polyposis coli (APC) mutations in adenomas from hereditary non-polyposis colorectal cancer patients
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DOI：
10.1016/s0304-3835(00)00486-9
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发表时间：
2000-09-01
期刊：
影响因子：
9.7
通讯作者：
Yuasa, Y
中科院分区：
文献类型：
--
作者：
Akiyama, Y;Nagasaki, H;Yuasa, Y
为了阐明腺瘤性大肠息肉病（APC）和β -catenin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例具有微卫星不稳定性（MSI）的HNPCC腺瘤中研究了它们的突变。7例（50%）腺瘤表现出体细胞APC突变，其中5例为移码突变，另外2例为无义突变。然而，这些腺瘤的APC突变谱与散发性结直肠肿瘤相似。2例（14.3%）未检测到APC改变的腺瘤显示β -连环蛋白密码子45 （TCT到TTT或CCT）错义突变。β -catenin突变的腺瘤MSI频率显著高于apcone突变（P < 0.001），表明-catenin突变与MSI密切相关，而APC突变与MSI密切相关。这些数据表明，β -连环蛋白激活突变的腺瘤和APC失活突变的腺瘤可能是HNPCC结直肠癌的前体。(C) 2000爱思唯尔科学爱尔兰有限公司版权所有。
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 -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. (C) 2000 Elsevier Science Ireland Ltd. All rights reserved.