LOSS OF HETEROZYGOSITY OF MCC IS NOT ASSOCIATED WITH MUTATION OF THE RETAINED ALLELE IN SPORADIC COLORECTAL-CANCER

The adenomatous polyposis coil (APC) gene, which transmits familial ad enomatous polyposis, is frequently mutated in sporadic colorectal tumo urs. Acquired somatic mutations have also been reported in a second ge ne, mutated in colorectal cancer (MCC), which lies within 500 kb of AP C on chromosome 5q21 and has thus been implicated in tumour developmen t. Further evidence for an oncosuppressor gene other than APC on chrom osome 5q comes from recent studies of lung, renal and hepatic cancers in which there is loss of heterozygosity of 5q21 but no somatic APC mu tations. To investigate the relative importance of APC and MCC in spor adic colorectal cancer, we have assessed the extent of 5q21 allelic lo ss in 80 carcinomas. All informative tumours exhibiting allelic loss h ad 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 ev ent, and that in cases where allele loss occurs mutation of the retain ed allele is uncommon. This suggests that MCC does not function as an independent tumour suppressor in the majority of colorectal cancers.