Genetic alterations in gastric cancers from British patients

Twenty-six gastric carcinoma and matching normal tissue DNAs, which had pre viously been analyzed for alterations of the APC (adenomatous polyposis coi l) and MCC (mutated in colorectal cancer) genes were further investigated f or the following genetic alterations: mutation and loss of heterozygosity ( LOH) of the p53 gene, replication error (RER) and LOH at 12 microsatellite repeat loci, and mutation of the hMSH2 gene. In addition, 9 of the 26 gastr ic carcinomas were analyzed for genetic alterations using comparative genom ic hybridization (CGH). Somatic mutations of the p53 gene were found to be frequent being detected in 31% of gastric carcinomas while LOH at the p53 l ocus was observed in 37.5% of informative cases. Loss of wild type p53 alle le was detected in the majority (7 of 8) tumors found to be harboring a mut ation. In the hMSH2 gene, an intronic 4 base pair insertion at 31 base pair s upstream of the beginning of exon 13 was detected in both tumor and norma l tissue from one gastric carcinoma case. RER was detected in 11.5% of gast ric carcinomas, at one or more microsatellite repeat loci. Of the 12 micros atellite repeat loci analyzed LOW was most frequently observed at D22S351 ( 30% informative cases) suggesting that a tumor suppressor gene on 22q may b e important in gastric carcinogenesis. In support of this, CGH analysis car ried out on 9 of the gastric carcinomas identified loss of chromosome 22 in 5 of these tumors. (C) 2001 Elsevier Science Inc. All rights reserved.