Contribution of molecular oncology in the detection of colorectal carcinomas

The development of effective screening tests for colorectal tumors is essential given the high frequency of these cancers in the general population, and more especially in various groups at risk. Sporadic and hereditary colorectal cancers result from the accumulation of mutations in oncogenes, such as ras, myc, neu/HER2, and in tumor suppressor genes such as apc, dcc, p53. The detection of ras or p53 mutations in DNA extracted from stool has been shown to be feasible and might be useful for the development of new screening tests. Many mutations in these genes can also be used as new prognostic factors. Identification of mutation in the apc gene responsible for familial polyposis, or its indirect detection through the study of polymorphism in such families, is completely changing the previously recommended medical attitude for the screening of this disease, and therefore may decrease or even avoid major medical follow-up. These changes are also true for the nonpolyposis hereditary colorectal tumors, also called Lynch syndrome, since the responsible hMSH2, hMLH1, hPMS1 and hPMS2 genes have recently been cloned. Mutations in these genes do not seem to be limited to families with Lynch syndrome, and could account for a predisposition of some patients to develop colorectal or other tumors.