Genetic aspects of colorectal cancer: the surgeon's view.
A characteristic feature of colorectal cancer genesis is its stepwise progression, which offers unique possibilities for studying its development. There are two principal kinds of mutation leading to uncontrolled cell proliferation and cancer. The first renders a stimulatory gene hyperactive--generation of an oncogene--and the second is the inactivation of a tumour suppressor gene. Current knowledge suggest that the change from normal mucosa to a small adenoma may be mediated by mutations of the APC gene and MCC gene on chromosome 5, by chromosome 5 deletion, by c-myc activation, and by DNA hypomethylation. The development to a large adenoma may be caused by Ki-ras mutation and further change 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 genetic markers for metastatic disease is under progress.
Dept. of Surgery, University Hospital, Linköping, Sweden.
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Sjödahl
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Nyström
D000236:Adenoma / Q000235:genetics / Q000473:pathology; D015179:Colorectal Neoplasms / Q000175:diagnosis / Q000235:genetics* / Q000473:pathology / Q000628:therapy; D003123:Colorectal Neoplasms, Hereditary Nonpolyposis; D016147:Genes, Tumor Suppressor; D006801:Humans; D009362:Neoplasm Metastasis; D009857:Oncogenes; D011379:Prognosis