LOSS OF HETEROZYGOSITY AND K-RAS GENE-MUTATIONS IN GASTRIC-CANCER

In order to identify relevant genetic lesions in gastric carcinoma, we searched for tumor suppressor gene inactivation and K-ras gene mutati ons by analyzing tumor and control DNAs from 34 patients. These were f rom an epidemiologically defined area of Italy characterized by one of the world's highest incidences of stomach cancer. Allele losses were investigated by the Southern blotting procedure at 16 polymorphic loci on 11 different chromosomes. Our data demonstrate that chromosomal re gions 5q, 11p, 17p and 18q are frequently deleted, and that 7q and 13q chromosome arms are also involved, although at a lower frequency. Los s of heterozygosity (LOH) at region 11p was not found during other sur veys carried out on patients of different geographic origins. No speci fic combination of allelic losses could be recognized in the samples a nalyzed, the only exception being that tumors with 17p allelic loss al so showed LOH on the 18q region. When matching frequent LOH events and the stage of progression of the tumors, we observed a trend of associ ation between advanced stages and allelic losses on 17p and 18q chromo some arms. The analysis of K-ras, carried out by the polymerase chain reaction and denaturing gradient gel electrophoresis, demonstrated tra nsforming mutations in only 3 out of 32 cases. Colorectal tumorigenesi s proceeds by the accumulation of genetic alterations, including K-ras mutations and inactivation of tumor suppressor genes on the 5q, 17p a nd 18q regions. Our data indicate that, although gastric and colorecta l neoplasias share common genetic alterations, they probably progress through different pathways.