Loss of heterozygosity of MCC is not associated with mutation of the retained allele in sporadic colorectal cancer.

The adenomatous polyposis coli (APC) gene, which transmits familial adenomatous polyposis, is frequently mutated in sporadic colorectal tumours. Acquired somatic mutations have also been reported in a second gene, mutated in colorectal cancer (MCC), which lies within 500 kb of APC on chromosome 5q21 and has thus been implicated in tumour development. Further evidence for an oncosuppressor gene other than APC on chromosome 5q comes from recent studies of lung, renal and hepatic cancers in which there is loss of heterozygosity of 5q21 but no somatic APC mutations. To investigate the relative importance of APC and MCC in sporadic colorectal cancer, we have assessed the extent of 5q21 allelic loss in 80 carcinomas. All informative tumours exhibiting allelic loss had deletions which included both APC and MCC. In 21 tumours with loss of heterozygosity in MCC we have screened the entire coding region of the gene for mutation of the retained allele and found no evidence for mutation. The data indicate that independent loss of MCC is a rare event, and that in cases where allele loss occurs mutation of the retained allele is uncommon. This suggests that MCC does not function as an independent tumour suppressor in the majority of colorectal cancers.