MUTATIONAL HOTSPOT IN THE P53 GENE IN HUMAN HEPATOCELLULAR CARCINOMAS

HUMAN hepatocellular carcinomas (HCC) from patients in Qidong, an area of high incidence in China, in which both hepatitis B virus and aflatoxin B1 are risk factors 1, were analysed for mutations in p53, a putative tumour-suppressor gene. Eight of the 16 HCC had a point mutation at the third base position of codon 249. The G --> T transversion in seven HCC DNA samples and the G --> C transversion in the other HCC are consistent with mutations caused by aflatoxin B1 in mutagenesis experiments 2,3. No mutations were found in exons 5, 6, 8 or the remainder of exon 7. These results contrast with p53 mutations previously reported in carcinomas and sarcomas of human lung, colon, oesophagus and breast; these are primarily scattered over four of the five evolutionarily conserved domains, which include codon 249 (refs 4-9). We suggest that the mutant p53 protein may be responsible for a selective clonal expansion of hepatocytes during carcinogenesis.