Molecular genetics of colon cancer: Recent advances and clinical implications

The pathogenesis of colorectal cancer has been the focus of recent molecular research. The adenoma-carcinoma sequence in colorectal cancer and its molecular alterations have been studied extensively and form the basis of multi-step-carcinogenesis. Furthermore, the identification of molecular alterations in hereditary colorectal cancer syndromes and sporadic colorectal cancer has changed the clinical management of these patients. Germline mutations of the APC gene are the basis for the development of familial adenomatous polyposis (FAP) and the detection of germline APC mutations in families with FAP determines their clinical follow-up. The presence of microsatellite instability has led to the detection of germline mutations of mismatch repair genes in hereditary non-polyposis colorectal cancer. In sporadic colorectal cancer specific genetic alterations, such as APC, K-ras, p53-gene mutations, have been ascribed to specific histomorphological alterations, constituting the molecular basis of the "adenoma-carcinoma-sequence". In addition, mutations of mismatch repair genes have also been described in sporadic colorectal cancer. The "de novo" carcinogenesis of colorectal cancer has been described recently and in a recent analysis adenomas have also been demonstrated to be of polyclonal origin. Thus besides the "traditional" concept of the adenoma-carcinoma-sequence, further models of colorectal carcinogenesis have to be taken into account.