Analysis of chromosome 17p13 (p53 locus) alterations in gastric carcinoma cells by dual-color fluorescence in situ hybridization.

Chromosome 17 and p53 gene locus alterations were determined on 67 gastric carcinomas by dual-color fluorescence in situ hybridization, using probes for centromere 17 and the 17p13.1 (p53 locus). The results were compared with loss of heterozygosity (LOH) at 17p13.3, direct sequencing of exons 5 to 9 of p53, and nuclear overexpression of p53 protein. Deletion of p53 was found in 26 of 67 tumors (39%). All 26 also showed LOH at 17p13.3, frequently overexpressed p53 protein, and had polysomy 17. The functional loss of p53 gene in these tumors, 85% of which were of intestinal type, appears to be caused by both deletion of 17p13.1 and missense mutation of the remaining allele. There were 9 tumors that had neither deletion nor LOH but had a large proportion of cancer cells that overexpressed p53 election. Despite evidence of LOH, there was no p53 deletion in 11 tumors. Finally, 21 tumors, mostly of diffuse type, showed neither deletions, LOH, nor p53 overexpression. Our data suggest that in gastric cancer, deletion of 17p is principally responsible for the allelic loss at the p53 gene and that analysis of deletions by the dual-color fluorescence in situ hybridization is a sensitive and useful approach to clarify chromosomal aberrations.