Analysis of p53 anti-oncogene in hepatocellular carcinoma

我们分析了20个肝细胞癌（HCC）来自日本的p53基因的限制性片段长度多态性的改变和核酸突变的聚合酶链反应与直接测序。20例HCC中有6例（30%）存在p53基因相关改变。14例杂合子病例中有5例发生17号染色体等位基因丢失（36%）。在3例（15%）病例中检测到p53基因突变，分别位于密码子176（外显子5）、236（外显子7）和294（外显子8），这与中国和南非的HCC病例不同，其中一半病例中报告的p53基因点突变位于相同的密码子249，黄曲霉毒素食物污染和B型肝炎病毒感染是HCC的公认危险因素。在小于3cm或早期肝癌中未发现p53基因改变。在日本，p53基因改变似乎是肝癌发生发展的晚期事件，这通常与丙型肝炎或B病毒的持续感染有关，但通常与暴露于黄曲霉毒素无关。

We analyzed 20 hepatocellular carcinomas (HCC) form Japan for alteration of the p53 gene by restriction fragment length polymorphisms and for nucleic acid mutations by polymerase chain reaction with direct sequencing. Alterations associated with the p53 gene were found in 6 out of 20 HCCs (30%). Allelic loss of chromosome 17p occurred in 5 out of 14 informative (heterozygous) cases (36%). Mutations in the p53 gene were detected in 3 cases (15%), at codons 176 (exon 5), 236 (exon 7) and 294 (exon 8), which were different from the HCC cases from China and South Africa, where point mutations in the p53 gene were reported at the same codon 249 in half of the cases, and where aflatoxin food contamination and hepatitis B virus infection are recognized risk factors of HCC. No p53 gene alterations were found in smaller HCCs (<3 cm) or at earlier stages. In Japan, p53 gene alterations seem to be a late event in the progression of hepatocarcinogenesis, which is often associated with persistent infection by the hepatitis C or B virus, but not usually with exposure to aflatoxin.