APC gene

Adenomatous polyposis coli (APC) gene A tumor suppressor gene, acting as a gatekeeper to prevent development of tumors. A familial cancer syndrome called FAP, or familial adenomatous polyposis, is caused by mutations in APC. Mutation of APC also occurs commonly in sporadic cases of colorectal carcinoma. 

Without regard to therapy, potentially valuable diagnostic tests are available for presymptomatic evaluation of risk of breast cancer due to predisposition from BRCA 1 or BRCA 2 and of colon cancer related to familial adenomatous polyposis (APC gene) or hereditary nonpolyposis mismatch repair genes (MSH 2). Genetic predisposition to Alzheimer disease associated with ApoE4 is neither sufficient nor necessary to lead to the clinical condition, and no definitive therapy is available. 

There is a disease termed hereditary polyposis. Victims develop a very large number of polyps in their colons, sometimes several thousand. Since the development of a colon polyp is the first step on the road to colon carcinoma, they are at high risk of colon cancer. The associated mutation is in a gene known as the APC gene. 

There are two major forms of hereditary susceptibility to colon cancer.00 Familial adenomatous polyposis is caused by defects in the APC gene (see Chapter 32). The more common hereditary nonpolyposis colorectal cancer (HNPCC), which includes many endometrial, stomach, and urinary tract tumors, results from defects in DNA mismatch repair. -)) The proteins hMSH2 and hMSLl are homologs of the E.coli MutS and MutL (main text). 

Mutations of the human APC gene are associated with both sporadic and familial forms of colon cancer. The APC protein is a large, multi-domain protein that has a 55-residue, N-terminal dimeric coiled coil (APC-55). Alber and colleagues used rules of thumb and those derived from an analysis of the covariation of a d and d d pairs in the cytokeratins (which form obligate heterodimers) to create a mutant of APC-55, anti-APCpl, as a potential probe for the APC protein (Sharma et al, 1998). 

Somatic mutations of the APC gene are found in more than 70% of all adenomatous polyps and carcinomas of the colon and rectum. It has been estimated that about 50% of the population in the Western world will develop colorectal polyps during a normal life span, as a consequence of/IPC mutations. (See ref 2-6). 

Rubinfeld, B Souza, B, Albert, 1., Muller, O., Chamberlain, S Masiarz, F., Munemitsu, S and Polakis, P (1993). Association of the APC gene product with p-catenin. Science2, 1731-1737. 

Beroud C, Soussi T. APC gene database of germline and somatic mutations in human tumors and cell lines. Nucleic Acids Res 1996 24 121-4. 

Brensinger JD, Taken SJ, Luce MC, Powell SM, Vance GH, Ahnen DJ, et al. Variable phenotype of familial adenomatous polyposis in pedigrees with 3 mutation in the APC gene. Gut 1998 43 548-52. 

Dobbie Z, Spycher M, Mary JL, Haner M, Gulden-schuh I, Hurlimaii R, et al. Correlation between the development of extracolonic manifestations in FAP patients and mutations beyond codon 1403 of the APC gene. J Med Genet 1996 33 274-80. 

Friedl W, Meuschel S, Caspar R, Lamberti C, Krieger S, SengteUer M, et al. Attenuated familial adenomatous polyposis due to a mutation in the 3 part of the APC gene a clue for understanding the function of the APC protein. Hum Genet 1996 97 579-84. 

Miyoshi Y, Nagase H, Ando H, Horii A, Ichii S, Nakatsuru S, et al. Somatic mutations of the APC gene in colorectal tumors mutation cluster region in the ARC gene. Hum Molec Genet 1992 1 229-33. 

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