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Colon tumor

Familial polyposis syndromes

Adenomatous polyposis coli (APC) gene


Reviewers: Shilpa Jain, M.D, New York University (see Reviewers page)
Revised: 30 March 2011, last major update March 2011
Copyright: (c) 2003-2011, PathologyOutlines.com, Inc.

Familial adenomatous polyposis-general
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● Familial adenomatous polyposis (FAP) is a rare autosomal dominant disease characterized by numerous colorectal polyps (usually more than 100) and with an incidence of colon adenocarcinoma approaching 100% (Gastroenterology 2003;124:544)
● However, it accounts only for < 1% of all colorectal carcinomas
● Diagnosis of FAP is based upon clinical and endoscopic findings

Three variants of FAP have been described based upon the clinical manifestations:
1. Gardner syndrome: associated with osteoma, desmoid tumors, cuteneous cysts and congenital hypetrophy of renal pigment epithelium
2. Turcot syndrome: associated with brain tumors
3. Attenuated FAP with less than 100 colorectal polyps

Familial adenomatous polyposis-molecular etiology
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● FAP is caused by germline mutation / deletion of the adenomatous polyposis coli (APC) tumor suppressor gene, located at the long arm of chromosome 5 (5q)
● However, 530% of FAP patients show no APC mutations by current genetic testing
● In APC-negative FAP patients, biallelic mutations of MutY human homologue (MYH) gene may be found
● The MYH gene encodes a member of the base excision repair pathway that is involved in repairing oxidative damage to DNA
● APC-negative FAP patients may have a family history compatible with recessive inheritance, indicating that this may be a different disease
● Genetic testing may be helpful for screening, diagnosis and management of atypical FAP cases
● PCR-based methods can detect APC germline mutations (Tech Coloproctol 2004;8 Suppl 2:s305)

APC gene physiology
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● APC is a gatekeeper gene that regulates the level of B catenin and directs the downstream activity of Wnt/b catenin pathways
● APC antagonizes the Wnt effector beta-catenin by promoting its proteosomal destruction, which directs beta-catenin away from the Tcf-Lef pathway (Dev Cell 2004;7:677)
● APC mutations promote the Tcf-Lef pathway and inhibit the cellular adhesion complex; overall, this stimulates cell proliferation (Mol Cancer 2003;2:41)

End of Colon tumor > Familial polyposis syndromes > Adenomatous polyposis coli (APC) gene


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