Characterization of six tumor suppressor genes and microsatellite instability in hepatocellular carcinoma in southern African blacks

Abstract

AIM:To analyse cumulative loss of heterozygosity (LOH) of chromosomal regions and tumor suppressor genes in hepatocellular carcinomas (HCCs) from 20 southern African blacks.METHODS: p53,RB1, BRCA1, BRCA2, WT1 and E-cadherin genes were analysed for LOH, and p53 gene was also analysed for the codon 249 mutation, in tumor and adjacent non tumorous liver tissues using molecular techniques and 10 polymorphic microsatellite markers.RESULTS:p53 codon 249 mutation was found in 25% of the subjects,as was expected, because many patients were from Mozambique, a country with high aflatoxin B-1 exposure. LOH was found at the RB1, BRCA2 and WT1 loci in 20%(4/20) of the HCCs, supporting a possible role of these genes in HCC. No LOH was evident in any of the remaining genes. Reports of mutations of p53 and RB1 genes in combination, described in other populations, were not confirmed in this study. Change in microsatellite repeat number was noted at 9/10 microsatellite loci in different HCCs, and changes at two or more loci were detected in 15%(3/20) of subjects.CONCLUSION:We propose that microsatellite/genomic instability may play a role in the pathogenesis of a subset of HCCs in black Africans.