Analysis of p53 anti-oncogene in hepatocellular carcinoma

我们用限制性片段长度多态性分析了日本20例肝细胞癌（HCC）中p53基因的改变，用直接测序的聚合酶链反应分析了核酸突变。20例hcc中有6例（30%）发现与p53基因相关的改变。14例信息丰富（杂合）病例中有5例（36%）发生17p染色体等位基因丢失。p53基因突变3例（15%），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，中国和南非一半的病例中p53基因在同一密码子249处发生点突变，黄曲霉毒素、食品污染和乙型肝炎病毒感染是公认的HCC危险因素。在较小的hcc （< 3cm）或早期阶段未发现p53基因改变。在日本，p53基因改变似乎是肝癌发生进展的晚期事件，这通常与丙型肝炎或乙型肝炎病毒的持续感染有关，但通常与黄曲霉毒素接触无关。

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.