Colon tumor
Familial polyposis syndromes
Adenomatous polyposis coli (APC) gene

Author: Amber El-Halaby, M.D. (see Authors page)
Editor: Raul Gonzalez, M.D.

Revised: 27 December 2016, last major update August 2015

Copyright: (c) 2002-2016, PathologyOutlines.com, Inc.

PubMed Search: Adenomatous polyposis coli gene [title]

Cite this page: Adenomatous polyposis coli (APC) gene and colon. PathologyOutlines.com website. http://www.pathologyoutlines.com/topic/colontumorAPCgene.html. Accessed May 27th, 2017.
Definition / general
  • APC is a tumor suppressor "gatekeeper" gene located on 5q that regulates the level of beta-catenin and directs the downstream activity of Wnt / beta-catenin pathways (Appl Clin Genet 2015;8:95)
  • APC contributes to orderly migration of intestinal cells within the crypt and beta-catenin plays a crucial role in this function; it also plays a role in intercellular adhesion
  • Germline mutations in APC have various manifestations, often based on the position of the mutation (among other factors):
    • Classic familial adenomatous polyposis (FAP): mutations occur between exon 5 and 5' portion of exon 15; severe polyposis (< 5000 colorectal polyps) associated with mutations between codons 1250 and 1464
    • Attenuated FAP: < 100 colorectal adenomas (average 30), later age of onset (< 40 years old); due to mutations at the extreme 5' or 3' ends or in region of exon 9
    • Gardner syndrome: variant of FAP with benign osteoid tumors and epidermoid skin cysts
    • Hereditary desmoid disease
    • Turcot syndrome: multiple colorectal polyps and medulloblastoma
    • Congenital hypertrophy of retinal pigment epithelium: benign finding, but can identify individuals at risk for FAP (Acta Ophthalmol Scand 1996;74:338)
    • Missense mutation does not lead to classic FAP but increases risk for colorectal carcinoma; found in Ashkenazi Jewish ancestry
Diagrams / tables

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Indications for patient testing

Molecular / cytogenetics description
  • 90% of cases of classic FAP are caused by germline mutation of APC (Clin Gastroenterol Hepatol 2014;12:1059)
  • More than 1500 germline mutations exist, the majority being point mutations (Colon Cancer Gene Variant Databases)
  • Exon 15 is the most common target for mutations, at codons 1061 and 1309 (Hum Mol Genet 2001;10:721)
  • Mutations are mostly nonsense or frameshift, resulting in a truncated protein
  • Biallelic inactivation leads to a loss of protein function (Genet Med 2014;16:101), which causes aberrant transcription of c-myc, cyclin D1 and others
  • APC mutations promote the T cell factor-lymphoid enhancer factor (TCF-LEF) pathway and inhibit the cellular adhesion complex, thereby stimulating cell proliferation (Mol Cancer 2003;2:41)
  • The gold standard for mutation detection is direct DNA sequencing of all 15 coding exons
  • Various other methods are available to detect point mutations, including PCR based methods (Tech Coloproctol 2004;8:s305)
Molecular / cytogenetics images

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Overview of mutations

Differential diagnosis
  • In FAP-like patients without APC mutation, biallelic mutations of MUTY human homologue (MYH) gene may be found (MUTYH associated polyposis)
  • 10% of patients with classic FAP phenotype do not have identifiable mutations in APC or MYH