FREQUENCY AND SPECTRUM OF P53 MUTATIONS IN GASTRIC-CANCER - A MOLECULAR-GENETIC AND IMMUNOHISTOCHEMICAL STUDY

The p53 tumour-suppressor gene plays an important role in gastric carc inogenesis. In an analysis of the spectrum of mutations of the p53 gen e seen in 56 primary gastric carcinomas of various types and grades of differentiation, the entire coding sequence (exons 2-11) of the p53 g ene was screened by single-strand conformation polymorphism analysis a nd direct genomic sequencing of polymerase chain reaction products. In tragenic restriction site polymorphisms and the probe YNZ22 were used for the detection of loss of heterozygosity (LOH) of the p53 gene locu s on chromosome 17p. p53 overexpression was studied with the anti-p53 antibody CM-1. A total of 21 somatic alterations of the p53 gene were found. Twenty were base-pair substitutions, and one was an eight basep air deletion. Six tumours with p53 mutations revealed LOH. Abnormaliti es in p53 expression were found in 17 tumour samples, of which 16 had gene mutations. The spectrum of mutations observed was consistent with the predicted spectrum for dietary mutagens associated with the metab olism of nitrogenous compounds, resulting in deamination of nucleic ac ids. Our findings suggest that p53 could be a primary target for mutat ions associated with dietary carcinogens in gastric carcinogenesis.