The frequency of p53 mutations in human primary gastric cancer was analyzed. RNA was extracted from 30 primary cancer tissues and RT-PCR was performed to amplify p53 cDNA. Codons 114 to 325 of p53, where well conserved and frequently mutating areas reside, were amplified using three sets of primers. RT-PCR products were analyzed for the presence of mutations by single strand conformation polymorphism assays. Sixteen of primary cancer samples showed shifted mobility in at least one of the analyzed areas. Sequence analysis confirmed the presence of p53 mutations in all samples with shifted mobility in single strand conformation polymorphism assays. Fourteen of the thirty samples had amino acid substitutions due to point mutations and/or frame shifts. Two samples had only a nonsense point mutation. Mutations were clustered in two different areas of die p53 gene, codons 135 to 185 on exon 5 and codons 261 to 285 on exon 8, with a diversity of mutation patterns. A simultaneously and independently performed immunohistochemical study of p53 expression in these cancer tissues showed a relatively good, but not an absolute, correlation with the presence of the mutated p53. The p53 mutation appears to be the first major alteration of cellular genes in human primary gastric cancer.

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