ABSENCE OF FREQUENT INVOLVEMENT OF MODIFIER OF MIN(APC) IN SPORADIC COLORECTAL-CANCER

Background: Mutations in the multiple intestinal neoplasia (Min) gene, the mouse homologue of the APC gene, result in the development of int estinal tumors. The degree of tumor expression is suppressed by the mo difier of Min (MOM). Alterations in the MOM gene result in markedly in creased tumor expression in the mouse. The human homologue of the MOM gene has been mapped to a locus on chromosome 1p35-36, but the role of the MOM gene in the development of human sporadic colorectal cancers has not been defined. Methods: The microsatellite marker D1S199 has be en previously mapped to the region of the MOM gene and was used as a p rimer for PCR amplification. The PCR products were subjected to denatu ring electrophoresis and analyzed for loss of heterozygosity (LOH) and the mismatch repair phenomenon (RER) of each tumor compared to its mu cosal control. Results: 48 consecutive sporadic colorectal cancers and normal adjacent mucosa were analyzed. LOH was noted in 2 of 48 tumors and the RER phenomenon was noted in 6 of 48 tumors. Thus, 8 of 48 tum ors (16.7%) showed alterations in the region of the locus of the MOM g ene. There was no association between alterations in this region and T NM stage, disease-free survival, overall survival, or p53 mutation. Co nclusions: Although mutation of the APC gene is an integral component of sporadic colorectal carcinogenesis, alteration in the region includ ing the MOM gene does not appear to play a significant role in the dev elopment or clinicopathologic behavior of human sporadic colorectal tu mors.