Alterations of p73 preferentially occur in gastric adenocarcinomas with foveolar epithelial phenotype.
To establish the possible involvement of p73, a newly discovered p53-related 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 adenocarcinomas. Of these, 32 exhibited the heterozygous p73 allele for the StyI restriction site in exon 2. Among these, the cancer DNA of 12 revealed loss of heterozygosity (LOH) of p73. All of the cancers with p73 LOH exhibited 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 allele of LOH-positive cancers. Our results suggest that alterations of p73, including LOH and abnormal expression, may play roles in the genesis of foveolar-type gastric adenocarcinomas, though this is not in line with a classical Knudson's "2-hit" model.
Yokozaki
H
H
First Department of Pathology, Hiroshima University School of Medicine, Hiroshima, Japan. hyoko@mcai.med.hiroshima-u.ac.jp
Shitara
Y
Y
Fujimoto
J
J
Hiyama
T
T
Yasui
W
W
Tahara
E
E
D000230:Adenocarcinoma / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D000368:Aged; D000483:Alleles; D004252:DNA Mutational Analysis; D004268:DNA-Binding Proteins / Q000096:biosynthesis / Q000235:genetics*; D004848:Epithelium / Q000473:pathology; D005260:Female; D016147:Genes, Tumor Suppressor; D006801:Humans; D019656:Loss of Heterozygosity; D008297:Male; D008875:Middle Aged; D009687:Nuclear Proteins / Q000096:biosynthesis / Q000235:genetics*; D010641:Phenotype; D013274:Stomach Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D000072160:Tumor Protein p73; D025521:Tumor Suppressor Proteins
D004268:DNA-Binding Proteins; D009687:Nuclear Proteins; C000606460:TP73 protein, human; D000072160:Tumor Protein p73; D025521:Tumor Suppressor Proteins