P53 GENE MUTATION SPECTRUM IN HEPATOCELLULAR CARCINOMAS IN HONG-KONG CHINESE

To examine the significance of mutation of the p53 tumour suppressor g ene in the development of human hepatocellular carcinoma in a high-pre valence area for hepatitis B viral infection but a low-exposure area f or aflatoxin B1, the spectrum of p53 gene mutations was examined in 21 tumour samples from Hong Kong Chinese patients, all of whom were HBsA g positive. DNA sequencing covering exons 5 to 9 of the p53 gene and H ae III restriction enzyme digestion for preliminary assessment of muta tion at codon 249 were performed. Immunohistochemical staining with an ti-p53 monoclonal antibodies was done on both tumour and nontumour liv er tissues. Six tumours (28.6%) showed a p53 mutation and all were poi nt mutations. Of the six point mutations, two (9.5%) were at codon 249 and both were G to T transversions (AGG-->ATG and AGG-->AGT transvers ions). The remaining point mutations were transversions scattered at c odon 172 (exon 5), 214 (exon 6), 273 (exon 8) and 330 (exon 9). Mutate d p53 protein was detected in five of these six cases with demonstrabl e point mutations by DNA sequencing, in contrast to none detected in a ll of the 15 cases without demonstrable point mutations. The presence of p53 mutations, including those at codon 249, did not show a signifi cant association with tumour size, sex, age, tumour invasiveness in te rms of liver invasion, microsatellites and venous permeation, cirrhosi s and encapsulation, but tumours with low cellular differentiation ten ded to have a higher incidence (71%) of point mutations than those wit h high cellular differentiation (8%). In conclusion, both the overall p53 mutation rate and that at codon 249 in HCC in Hong Kong Chinese ar e lower than those reported in tumours from China and sub-Saharan Afri ca. The low mutation rate at codon 249 is compatible with a low aflato xin exposure. A special type of p53 mutation has not been found to be associated with hepatitis B viral infection. Mutations of p53 gene ten ds to occur in tumours with low cellular differentiation, suggesting a late occurrence in the event of tumour progression.