P300 gene alterations in intestinal and diffuse types of gastric carcinoma.

Abstract

p300 is a transcriptional coactivator, and bi-allelic mutations of the p300 gene have been demonstrated in human cancers. In 80 gastric carcinoma tissues, loss of heterozygosity (LOH) was analyzed by polymerase chain reaction (PCR) analysis, using 14 primer pairs at the 22q11-13 locus containing NF2 and p300. The mutations of the p300 gene were examined by reverse transcriptase-PCR (RT-PCR) and single-stranded conformation polymorphism (SSCP) analysis. LOH was frequently observed at the 22q13 locus containing the p300 gene in gastric carcinomas, with an equal frequency in the intestinal (21/34) and diffuse (30/46) types. However, LOH was significantly correlated with advanced stage and lymph node metastasis only in the intestinal type. Using RT-PCR-SSCP analysis, mutations of the p300 gene were identified in the intestinal (6/15) and in the diffuse (4/18) types, but all of the mutations were accompanied by LOH at the 22q13 locus only in the intestinal type. The p300 gene behaves as a tumor suppressor gene in the intestinal, but not in the diffuse type of gastric carcinoma. The significance of frequent gene alteration in the diffuse type should be further investigated by the clarification of other mechanisms of p300 inactivation and by clarification or of the functional role of p300 in cell adhesion/spreading.