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Familial adenomatous polyposis (FAP)

Identity

Other namesAdenomatous polyposis of the colon
Gardner syndrome
Inheritance autosomal dominant disorder; frequency is about 2.5/105 newborns; neomutation in 20%; variable expressivity; penetrance close to 100% by the age of 40 yrs.

Clinics

Phenotype and clinics
  • multiple adenomatous polyps of the colon and the rectum
  • polyps also develop in the upper gastrointestinal tract
  • other: pigmented retinal lesions (congenital hypertrophy of the retinal pigment epithelium), jaw cysts, sebaceous cysts, desmoid tumours, and osteomas.
  • Neoplastic risk - colorectal cancer(s) develop from the polyps through a dysplastic stage
    - malignancies may be found in other sites: liver (hepatoblastoma), brain (medulloblastoma), thyroid.
    Prognosis colorectal cancer in early adult life (median age: 40 yrs) is the first cause of death in this disease.

    Genes involved and Proteins

     
    Gene NameAPC
    Location 5q21
    Protein
    Description tumour suppressor gene; the APC normal gene product interacts with the adherens junction proteins a and -catenin
    Mutations
    Germinal FAP is caused by a highly heterogeneous spectrum of point mutations that represents a problem for molecular genetic diagnosis; but all the mutations are chain terminating and some correlations between the position of the mutation and the phenotypic consequences have been described:
    - germline mutations between codons 1250 and 1464 are associated with profuse polyposis;
    - an attenuated adenomatous polyposis coli (AAPC) is associated with mutations located very close to the 5-prime end of the APC gene;
    - the extent of congenital hypertrophy of the retinal pigment epithelium (CHRPE) depends on the position of the protein-truncating mutation in APC; CHRPE lesions are almost always absent if the mutation occur before exon 9, but are consistently present if it occurs after this exon;
    - patients with a mutation between codons 1445 and 1578 do not express CHRPE; however, these patients developed severe desmoid tumors.

    External links

    OMIM175100
    OrphanetFamilial adenomatous polyposis
    HGMD119682
    Other databaseFamilial Adenomatous Polyposis - GeneClinics

    Bibliography

    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
     
    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
     
    Lessons from hereditary colorectal cancer.
    Kinzler KW, Vogelstein B
    Cell. 1996 ; 87 (2) : 159-170.
    PMID 8861899
     
    Restriction of ocular fundus lesions to a specific subgroup of APC mutations in adenomatous polyposis coli patients.
    Olschwang S, Tiret A, Laurent-Puig P, Muleris M, Parc R, Thomas G
    Cell. 1993 ; 75 (5) : 959-968.
    PMID 8252631
     
    REVIEW articlesautomatic search in PubMed
    Last year articlesautomatic search in PubMed

    Contributor(s)

    Written06-1998Sylviane Olschwang
    INSERM U434, Fondation Jean Dausset - C.E.P.H., 27, rue Juliette Dodu, 75010 Paris, France

    Citation

    This paper should be referenced as such :
    Olschwang, S
    Familial adenomatous polyposis (FAP)
    Atlas Genet Cytogenet Oncol Haematol. 1998;2(4):157-158.
    Free online version   Free pdf version   [Bibliographic record ]
    URL : http://AtlasGeneticsOncology.org/Kprones/adenom_pol.html

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    indexed on : Tue Aug 26 15:55:56 CEST 2014


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