Alterations of p73 preferentially occur in gastric adenocarcinomas with foveolar epithelial phenotype

To establish the possible involvement of p73, a newly discovered p53-relate d candidate as a tumor-suppressor gene in human stomach carcinogenesis, the allelic status, allele-specific expression and mutations of the gene were investigated using PCR-restriction fragment length polymorphism (PCR-RFLP) analysis, RT-PCR SSCP analysis and direct DNA sequencing in 95 gastric aden ocarcinomas. Of these, 32 exhibited the heterozygous p73 allele for the Sty 1 restriction site in exon 2, Among these, the cancer DNA of 12 revealed lo ss of heterozygosity (LOH) of p73, All of the cancers with p73 LOH exhibite d phenotypes of foveolar epithelium of the stomach, RT-PCR SSCP analysis of p73 heterozygous cases demonstrated not only bi-allelic expression of the gene but also relatively reduced expression of the affected allele in 6 of 8 tumors with p73 LOH, No gene mutation was detected in the remaining allel e of LOH-positive cancers. Our results suggest that alterations of p73, inc luding LOH and abnormal expression, may play roles in the genesis of foveol ar-type gastric adenocarcinomas, though this is not in line with a classica l Knudson's "2-hit" model. (C) 1999 Wiey-Liss, Inc.