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APC (adenomatous polyposis coli)

Written1998-04Richard Hamelin
INSERM U434, CEPH, 27, rue Juliette Dodu, 75010 Paris, France
Updated2005-03Jennifer S Tirnauer
Center for Molecular Medicine, University of Connecticut Health Center, 263 Farmington Avenue, E1032, Farmington, CT 06030-3101, USA

(Note : for Links provided by Atlas : click)

Identity

Other alias
LocusID (NCBI) 324
Atlas_Id 118
Location 5q22.2  [Link to chromosome band 5q22]
Location_base_pair Starts at and ends at bp from pter
 
  APC (5q21) - Courtesy Mariano Rocchi, Resources for Molecular Cytogenetics.
Fusion genes
(updated 2017)
Data from Atlas, Mitelman, Cosmic Fusion, Fusion Cancer, TCGA fusion databases with official HUGO symbols (see references in chromosomal bands)
APC (5q22.2) / ALDH1L1 (3q21.3)APC (5q22.2) / APC (5q22.2)APC (5q22.2) / KCNN2 (5q22.3)
APC (5q22.2) / KRT6A (12q13.13)APC (5q22.2) / RBMS1 (2q24.2)APC (5q22.2) / REEP2 (5q31.2)
APC (5q22.2) / SYTL4 (Xq22.1)ATP6AP2 (Xp11.4) / APC (5q22.2)PSMC2 (7q22.1) / APC (5q22.2)
RBMS1 (2q24.2) / APC (5q22.2)TPST1 (7q11.21) / APC (5q22.2)

DNA/RNA

Description 15 exons (with a particularly large 15th exon).
Transcription 9.0 kb mRNA; 8538 bp open reading frame.

Protein

Description 2843 amino acids; 310 kDa.
Function APC is a classical tumour suppressor protein. The APC gene product indirectly regulates transcription of a number of critical cell proliferation genes, through its interaction with the transcription factor beta catenin. APC binding to beta catenin leads to ubiquitin-mediated beta catenin destruction; loss of APC function increases transcription of beta catenin targets. These targets include cyclin D, C-myc, ephrins and caspases. APC also interacts with numerous actin and microtubule associated proteins. APC itself stabilizes microtubules. Homozygous APC truncation has been shown to affect chromosome attachment in cultured cells. Roles for APC in cell migration have been demonstrated in vitro and in mouse models.
Homology A second family member, APC2, is located on 19p13.3 (see non-annotated genes).

Mutations

Germinal Germline mutations of APC cause a spectrum of diseases under the broad category of familial adenomatous polyposis (FAP).
Mutations typically cluster in or just distal to the armadillo repeat region and truncate the protein near its middle. It is not known which is pathophysiologic - absence of the full-length protein or presence of the truncated version; evidence exists for both. The second hit creates another truncation or gene deletion. There is some evidence that the position of the first hit in the gene determines the pattern of the second hit.
Rare hypomorphic mutations cause attenuated polyposis.
Somatic Both copies of the APC gene are mutated in 80% of sporadic colorectal tumours.

Implicated in

Note
  
Entity Familial Adenomatous Polyposis (FAP)
Disease Autosomal dominant disease in which patients develop thousands of colonic polyps during childhood and adolescence. Many of these will progress to cancers if not removed.
FAP encompasses other disease syndromes with extra-colonic manifestations.

In Gardner Syndrome, patients may develop the following extra-intestinal manifestations:

  • Gastric and duodenal malignancies.
  • Cancer of the pancreas, biliary tree, and gallbladder.
  • Hepatoblastoma.
  • Congenital hypertrophy of the retinal pigment epithelium (CHRPE), a benign hyperpigmentation beneath the retina that is typically asymptomatic.
  • Desmoid tumors, a tumor of the connective tissue that can cause morbidity and mortality by impinging on adjacent structures.
  • Osteomas and dental abnormalities.
  • Epidermoid cysts and other skin abnormalities.

    In a subset of patients with Turcot's syndrome, intestinal polyposis due to APC mutation is associated with brain tumors, especially meduloblastoma.

  • Prognosis Without treatment, the life expectancy is in the early 40s due to colon cancer. Treatment consists of regular screening, with polypectomy of large lesions. Due to the large number of polyps, eventual complete colectomy with or without proctosigmoidectomy is needed. Regular use of the cyclooxygenase inhibitor Sulindac and possibly other member of this class of drugs reduces the number of polyps. About ten percent of patients also experience significant morbidity from desmoid tumors.
      
      
    Entity Sporadic colorectal cancer
    Disease Somatic mutation of the APC gene is found in the majority of colorectal adenocarcinomas. Sporadic colorectal cancer is the third most frequent cancer in the world.
    Prognosis The prognosis depends on the stage of the disease. Stage I lesions are usually cured by surgery. There is controversy about the use of chemotherapy in Stage II disease. In Stage III disease, chemotherapy improves the five year survival from ~50% to ~60%.
    Oncogenesis Loss of normal APC function is known to be an early event in both familial and sporadic colon cancer pathogenesis, occurring at the pre-adenoma stage. Current discussion is focused on whether loss of APC function precedes, follows, or is entwined with chromosomal instability. Later events include abnormalities of K-ras and p53.

    Generally colon cancers show either chromosomal instability (CIN), which correlates with loss of APC function, or microsatellite instability (MIN), which correlates with loss of mismatch repair function, but not both.

      

    Bibliography

    Biology of the adenomatous polyposis coli tumor suppressor.
    Goss KH, Groden J
    Journal of clinical oncology : official journal of the American Society of Clinical Oncology. 2000 ; 18 (9) : 1967-1979.
    PMID 10784639
     
    Identification and characterization of the familial adenomatous polyposis coli gene.
    Groden J, Thliveris A, Samowitz W, Carlson M, Gelbert L, Albertsen H, Joslyn G, Stevens J, Spirio L, Robertson M
    Cell. 1991 ; 66 (3) : 589-600.
    PMID 1651174
     
    Lessons from hereditary colorectal cancer.
    Kinzler KW, Vogelstein B
    Cell. 1996 ; 87 (2) : 159-170.
    PMID 8861899
     
    The adenomatous polyposis coli protein: the Achilles heel of the gut epithelium.
    Nä IS
    Annual review of cell and developmental biology. 2004 ; 20 : 337-366.
    PMID 15473844
     
    Mutations of chromosome 5q21 genes in FAP and colorectal cancer patients.
    Nishisho I, Nakamura Y, Miyoshi Y, Miki Y, Ando H, Horii A, Koyama K, Utsunomiya J, Baba S, Hedge P
    Science (New York, N.Y.). 1991 ; 253 (5020) : 665-669.
    PMID 1651563
     
    APC mutations occur early during colorectal tumorigenesis.
    Powell SM, Zilz N, Beazer-Barclay Y, Bryan TM, Hamilton SR, Thibodeau SN, Vogelstein B, Kinzler KW
    Nature. 1992 ; 359 (6392) : 235-237.
    PMID 1528264
     

    Citation

    This paper should be referenced as such :
    Tirnauer, J
    APC (adenomatous polyposis coli)
    Atlas Genet Cytogenet Oncol Haematol. 2005;9(2):132-133.
    Free journal version : [ pdf ]   [ DOI ]
    On line version : http://AtlasGeneticsOncology.org/Genes/APCID118.html
    History of this paper:
    Hamelin, P. APC (adenomatous polyposis coli). Atlas Genet Cytogenet Oncol Haematol. 1998;2(3):75-76.
    http://documents.irevues.inist.fr/bitstream/handle/2042/37429/04-1998-APC118.pdf


    Other Leukemias implicated (Data extracted from papers in the Atlas) [ 2 ]
      Primary mediastinal B-cell lymphoma (PMBL)
    t(3;21)(q26;q11) NRIP1/MECOM


    Other Solid tumors implicated (Data extracted from papers in the Atlas) [ 19 ]
      Head and Neck: Odontogenic tumor: Ameloblastoma
    Esophagus: Barrett's esophagus, dysplasia and adenocarcinoma
    Colon: Colorectal adenocarcinoma
    Soft Tissues: Desmoid-type fibromatosis
    Eye tumors: an overview
    Gastric Tumors: an overview
    Head and Neck: Epidermoid carcinoma
    Liver: Hepatoblastoma
    Liver: Hepatocellular carcinoma
    Liver: Adenoma
    Liver tumors: an overview
    Testis: Germ cell tumors
    Head and Neck: Oral squamous cell carcinoma
    Skin: Melanoma
    Soft tissue tumors: an overview
    Squamous cell cancer
    t(3;5)(q21;q22) APC/ALDH1L1
    t(5;5)(q22;q31) APC/REEP2
    t(5;12)(q22;q13) APC/KRT6A


    Other Cancer prone implicated (Data extracted from papers in the Atlas) [ 3 ]
      Familial adenomatous polyposis (FAP) Hereditary desmoid disease. Turcot syndrome


    External links

    Nomenclature
    Cards
    AtlasAPCID118.txt
    Aliases
    Genomic and cartography
    Gene and transcription
    RefSeq transcript (Entrez)
    RefSeq genomic (Entrez)
    SOURCE (Princeton)Expression in : [Datasets]   [Normal Tissue Atlas]  [carcinoma Classsification]  [NCI60]
    BioGPS (Tissue expression)324
    Protein : pattern, domain, 3D structure
    Domain families : Pfam (Sanger)
    Domain families : Pfam (NCBI)
    Protein Interaction databases
    Ontologies - Pathways
    Clinical trials, drugs, therapy
    Miscellaneous
    canSAR (ICR) (select the gene name)
    Other databaseUMD-APC (adenomatosis polyposis coli). Curators: C. Béroud and T. Soussi
    Other databaseAPC (Broad)
    Probes
    Litterature
    REVIEW articlesautomatic search in PubMed
    Last year publicationsautomatic search in PubMed


    © Atlas of Genetics and Cytogenetics in Oncology and Haematology
    indexed on : Thu Oct 18 17:28:25 CEST 2018

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