SELECTIVE G-MUTATION TO T-MUTATION OF P53 GENE IN HEPATOCELLULAR-CARCINOMA FROM SOUTHERN AFRICA

HEPATOCELLULAR carcinoma (HCC) is a prevalent cancer in sub-Saharan Africa and eastern Asia 1. Hepatitis B virus and aflatoxins are risk factors for HCC 2, but the molecular mechanism of human hepatocellular carcinogenesis is largely unknown 3. Abnormalities in the structure and expression of the tumour-suppressor gene p53 are frequent in HCC cell lines 4, and allelic losses from chromosome 17p have been found in HCCs from China 5 and Japan 6. Here we report on allelic deletions from chromosome 17p and mutations of the p53 gene found in 50% of primary HCCs from southern Africa. Four of five mutations detected were G --> T substitutions, with clustering at codon 249. This mutation specificity could reflect exposure to a specific carcinogen, one candidate being aflatoxin B1 (ref. 7), a food contaminant in Africa 8, which is both a mutagen that induces G to T substitution 9 and a liver-specific carcinogen 10.