Genetic changes of both p53 alleles associated with the conversion from colorectal adenoma to early carcinoma in familial adenomatous polyposis and non-familial adenomatous polyposis patients.

作者：Rei Kikuchi‐Yanoshita, Motoko Konishi, Sadayoshi Ito, Makoto Seki, Keitaro Tanaka, Yoshiharu Maeda, Haruhiko Iino, Masashi Fukayama, Masato Koike, Takahiro Mori · 发表于：PubMed · 年份：1992 · 被引用次数：183 · 研究领域：Genetic factors in colorectal cancer、Gastric Cancer Management and Outcomes、Colorectal and Anal Carcinomas

Mutation and loss of heterozygosity (LOH) in the p53 gene were analyzed in 274 colorectal tumors of 4 histopathological grades. Among 160 tumors from 40 familial adenomatous polyposis patients, none of 58 adenomas with moderate dysplasia had p53 mutations, whereas 8% (3 of 37) of severe adenomas, 15% (6 of 40) of intramucosal carcinomas, and 40% (10 of 25) of invasive carcinomas had p53 mutations. Only 3% (1 of 33) of severe adenomas showed both mutation and LOH, while 25% (6 of 24) of intramucosal carcinomas and 40% (10 of 25) of invasive carcinomas had both mutation and LOH. All intramucosal and invasive carcinomas that had mutations lost the other allele of the p53 gene. In 114 tumors from 86 non-familial adenomatous polyposis patients, similar results were obtained; no adenoma showed both mutation and LOH, but both alterations occurred in intramucosal and invasive carcinoma. As regards specificity in 56 mutations detected in the present study, the frequently affected codons were codons 175, 238, 245, 248, 273, and 282, 4 of these amino acids being arginine, and 72% (39 of 54) of all mutations were GC to AT transition. Although expression into p53 polyadenylated RNA was high in every invasive carcinoma irrespective of the presence of mutation or LOH, there was a correlation between mutation and protein level; immunostaining of p53 protein was negative in almost all adenomas, but it was positive in 86% of invasive carcinomas exhibiting p53 mutation. These data suggest that ...