The cellular and molecular pathogenesis of colorectal cancer.
The development of colorectal neoplasia originates from normal colonic mucosa, progresses to the adenomatous polyp, and later may evolve into carcinoma. This procession of histologic change can be defined by a series of successive waves of clonal expansion that contain certain genetic alterations. These genetic alterations include mutations in the K-ras oncogene and mutation in the one allele coupled with loss of the second allele for the tumor suppressor genes APC, DCC, and p53. The normal forms of these genes encode for proteins that regulate cell growth, cell-to-cell adhesion, and cell cycle checkpoints. Information on the function of these genes, as well as a proposed model of sequential mutation and loss of these regulatory genes during colorectal tumorigenesis are presented.
Carethers
J M
JM
Department of Medicine, University of California at San Diego, La Jolla, California, USA.
D011125:Adenomatous Polyposis Coli / Q000235:genetics; D000483:Alleles; D015179:Colorectal Neoplasms / Q000235:genetics* / Q000473:pathology; D018450:Disease Progression; D017353:Gene Deletion; D016147:Genes, Tumor Suppressor; D016158:Genes, p53; D006801:Humans; D018895:Microsatellite Repeats; D009857:Oncogenes