GENETIC-ASPECTS OF COLORECTAL-CANCER - THE SURGEONS VIEW

A characteristic feature of colorectal cancer genesis is its stepwise progression, which offers unique possibilities for studying its develo pment. There are two principal kinds of mutation leading to uncontroll ed cell proliferation and cancer. The first renders a stimulatory gene hyperactive-generation of an oncogene-and the second is the inactivat ion of a tumour suppressor gene. Current knowledge suggests that the c hange from normal mucosa to a small adenoma may be mediated by mutatio ns of the APC gene and MCC gene on chromosome 5, by chromosome 5 delet ion, by c-myc activation, and by DNA hypomethylation. The development to a large adenoma may be caused by Ki-ras mutations and further chang e to a dysplastic adenoma by deletion of the DCC gene on chromosome 18 , The ability to become an invasive carcinoma may then be mediated by p53 mutations and deletion of chromosome 17p. Identification of geneti c markers for metastatic disease is under progress.