Deletion mapping reveals two regions of chromosome 8 allele loss in colorectal carcinomas.

Colorectal carcinogenesis is associated with the accumulation of genetic changes involving both dominant oncogenes and tumor suppressor genes. Although at least four different genes have been implicated in the process, the detection of allele loss from other regions of the genome suggests the involvement of additional genes. The short arm of chromosome 8 is one of these regions; loss of heterozygosity occurs at rates ranging from 30 to 50%. To define the region of common deletion containing the putative tumor suppressor gene, we analyzed a series of 87 carcinomas for allele loss in different regions of the short arm of chromosome 8 by using Southern blot analysis and a panel of polymorphic probes. We found allele loss in 33% of our cases, which involves two separate regions, one in the p-terminal region of the chromosome, 8p23.1-pter, where 45% of informative cases demonstrated loss, and the other in the mid-p region, at 8p21, where 31% of cases showed allele loss. No tumors showed loss of heterozygosity for both regions. These findings suggest the presence of two discrete genes related to colorectal carcinogenesis on the short arm of chromosome 8.