Allelic imbalance in colorectal cancer at the CRAC1 locus in early-onset colorectal cancer

A susceptibility gene to colorectal adenomas and carcinoma (CRAC1) on chromosome region 15q14 approximately q22 has been proposed on the basis of linkage in a single family. Allele-specific loss of heterozygosity (LOH) in tumors of affected family members suggests that the causative gene functions as a tumor-suppressor gene. The genes that are mutated in inherited cancer syndromes are often involved in the pathogenesis of sporadic cancer. To determine whether CRAC1 plays a role in colorectal carcinogenesis in general, we have studied 277 cases of early-onset colorectal cancers for allele loss at 15q14 approximately q22 using four microsatellite markers (D15S970, D15S117, D15S971, and D15S1028) that define the region of maximal linkage. The frequency of LOH detected was between 14% and 22%, but there was no significant association between LOH at each adjacent marker. Most cancers caused by loss of expression of a tumor suppressor involve large-scale deletion of one allele. On this basis, our findings suggest that CRAC1 is unlikely to be implicated in the development of colorectal cancer in general or, if involved, it is through small somatic mutations or other loss of function mechanisms rather than allele loss.