Published online Dec 15, 1999. doi: 10.3748/wjg.v5.i6.470
Revised: September 9, 1999
Accepted: October 13, 1999
Published online: December 15, 1999
AIM: To analyse cumulative loss of heterozygosity (LOH) of ch romosomal regions and tumor suppressor genes in hepatocellular carcinomas (HCCs) from 20 southern African blacks.
METHODS: p53, RB1, BRCA1, BRCA2, WT1 and E-cadherin- ge nes 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 wit h high aflatoxin B1 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.