Murakami Y, Hayashi K, Hirohashi S, Sekiya T
Oncogene Division, National Cancer Center Research Institute, Tokyo, Japan.
Cancer Res. 1991 Oct 15;51(20):5520-5.
Aberrations of the p53 gene in 43 primary hepatocellular carcinomas (HCCs) were examined by single-strand conformation polymorphism analysis of polymerase chain reaction products. Of these hepatocellular carcinomas, 22 were advanced HCCs, and 21 were early HCCs. Structural abnormalities of the p53 gene were observed in eight of the 22 advanced HCCs, but in none of the early HCCs. Of the eight tumors with an abnormal p53 gene, seven had lost one of the two p53 alleles and, in the seven tumors with identifiable mutations, point mutations were found in four tumors and deletions of several nucleotides were observed in two tumors. The remaining one retained both alleles and carried two point mutations. In addition to the aberrations of the p53 gene, loss of the retinoblastoma gene or loss of heterozygosity at chromosome 13q was observed in six of seven informative cases of eight tumors carrying a mutated p53 gene. These results suggest the involvement of at least two tumor suppressor genes in a late stage of hepatocarcinogenesis.
通过聚合酶链反应产物的单链构象多态性分析，检测了43例原发性肝细胞癌（HCC）中p53基因的畸变情况。这些肝细胞癌中，22例为进展期HCC，21例为早期HCC。在22例进展期HCC中，有8例观察到p53基因的结构异常，但早期HCC中均未观察到。在8例p53基因异常的肿瘤中，7例丢失了两个p53等位基因中的一个，在7例可识别突变的肿瘤中，4例发现点突变，2例观察到几个核苷酸的缺失。其余1例保留了两个等位基因并携带两个点突变。除了p53基因的畸变外，在携带突变p53基因的8例肿瘤中，7例信息可分析的病例中有6例观察到视网膜母细胞瘤基因缺失或13q染色体杂合性缺失。这些结果表明，至少两个肿瘤抑制基因参与了肝癌发生的晚期阶段。
