Selective G to T mutations of p53 gene in hepatocellular carcinoma from southern Africa

HEPATOCELLULAR carcinoma (HCC) is a prevalent cancer in sub-Saharan Africa and eastern Asia1. Hepatitis B virus and aflatoxins are risk factors for HCC2, but the molecular mechanism of human hepatocellular carcinogenesis is largely unknown3. Abnormalities in the structure and expression of the tumour-suppressor gene p53 are frequent in HCC cell lines4, and allelic losses from chromosome 17p have been found in HCCs from China5 and Japan6. 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 Africa8, which is both a mutagen that induces G to T substitution9 and a liver-specific carcinogen10. © 1991 Nature Publishing Group.