Site-specific hypomethylation of the c-myc oncogene in human hepatocellular carcinoma.

In order to examine the effect of alteration in methylation of the c-myc gene on hepatocarcinogenesis, the extent of methylation of the c-myc gene was examined in 24 tissues of hepatocellular carcinoma (HCC), 24 adjacent non-tumor liver tissues from the same patients and 16 control liver tissues by the use of restriction endonucleases. The following results were obtained. (1) The c-myc gene from HCC tissue tended to be hypomethylated in comparison with that in non-tumor liver tissue from the same patient. (2) The c-myc gene from non-tumor liver tissue was hypomethylated to various degrees in comparison with that in control liver tissues. (3) The CCGG site in the third exon of the c-myc gene tended to be more extensively hypomethylated in HCC tissues than in non-tumor and control liver tissues. These results suggest that hypomethylation of the c-myc gene may occur to various degrees before the appearance of HCC, and may be associated with hepatocarcinogenesis. Moreover, the hypomethylation in the third exon of the c-myc gene is probably important for the development of HCC.

Mutation of the p53 tumor-suppressor gene is not a feature of endometrial hyperplasias.

OBJECTIVE: Mutation and overexpression of the p53 gene occur in approximately 20% of endometrial carcinomas. To determine whether alteration of the p53 gene is an early event in endometrial carcinogenesis, we examined the p53 gene in endometrial hyperplasias. STUDY DESIGN: Genomic deoxyribonucleic acid was extracted from 117 endometrial hyperplasias (36 simple, 40 complex, 41 atypical) and 30 endometrial cancers. Exons 5 through 8 of the p53 gene were amplified by means of the polymerase chain reaction. Mutations in the p53 gene were sought with single-stranded conformation polymorphism analysis and confirmed by direct deoxyribonucleic acid sequencing. RESULTS: None of 117 endometrial hyperplasias were found to have mutations in the p53 gene, whereas mutations were seen in three of 30 (10%) endometrial cancers (p < 0.02). The p53 mutations seen in three cancers were confirmed by direct sequencing (codons 157, 180, 272). CONCLUSION: Because it does not appear to be a feature of endometrial hyperplasias, mutation of the p53 gene may represent a relatively late event in endometrial carcinogenesis.