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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

Alias_namesregulatory subunit 46
Alias_symbol (synonym)DP2
DP3
DP2.5
PPP1R46
Other alias
HGNC (Hugo) APC
LocusID (NCBI) 324
Atlas_Id 118
Location 5q22.2  [Link to chromosome band 5q22]
Location_base_pair Starts at 112073556 and ends at 112181936 bp from pter ( according to hg19-Feb_2009)  [Mapping APC.png]
 
  APC (5q21) - Courtesy Mariano Rocchi, Resources for Molecular Cytogenetics.
Fusion genes
(updated 2016)
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) / 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) [ 16 ]
      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


    Other Cancer prone implicated (Data extracted from papers in the Atlas) [ 4 ]
      Familial adenomatous polyposis (FAP) Familial nervous system tumour syndromes Hereditary desmoid disease. Turcot syndrome


    External links

    Nomenclature
    HGNC (Hugo)APC   583
    LRG (Locus Reference Genomic)LRG_130
    Cards
    AtlasAPCID118
    Entrez_Gene (NCBI)APC  324  adenomatous polyposis coli
    AliasesBTPS2; DP2; DP2.5; DP3; 
    GS; PPP1R46
    GeneCards (Weizmann)APC
    Ensembl hg19 (Hinxton)ENSG00000134982 [Gene_View]  chr5:112073556-112181936 [Contig_View]  APC [Vega]
    Ensembl hg38 (Hinxton)ENSG00000134982 [Gene_View]  chr5:112073556-112181936 [Contig_View]  APC [Vega]
    ICGC DataPortalENSG00000134982
    TCGA cBioPortalAPC
    AceView (NCBI)APC
    Genatlas (Paris)APC
    WikiGenes324
    SOURCE (Princeton)APC
    Genetics Home Reference (NIH)APC
    Genomic and cartography
    GoldenPath hg19 (UCSC)APC  -     chr5:112073556-112181936 +  5q21-q22   [Description]    (hg19-Feb_2009)
    GoldenPath hg38 (UCSC)APC  -     5q21-q22   [Description]    (hg38-Dec_2013)
    EnsemblAPC - 5q21-q22 [CytoView hg19]  APC - 5q21-q22 [CytoView hg38]
    Mapping of homologs : NCBIAPC [Mapview hg19]  APC [Mapview hg38]
    OMIM114500   114550   135290   175100   175100   611731   613659   
    Gene and transcription
    Genbank (Entrez)AB210001 AF038181 AI492038 AK289567 AK294544
    RefSeq transcript (Entrez)NM_000038 NM_001127510 NM_001127511
    RefSeq genomic (Entrez)NC_000005 NC_018916 NG_008481 NT_034772 NW_004929323
    Consensus coding sequences : CCDS (NCBI)APC
    Cluster EST : UnigeneHs.158932 [ NCBI ]
    CGAP (NCI)Hs.158932
    Alternative Splicing GalleryENSG00000134982
    Gene ExpressionAPC [ NCBI-GEO ]   APC [ EBI - ARRAY_EXPRESS ]   APC [ SEEK ]   APC [ MEM ]
    Gene Expression Viewer (FireBrowse)APC [ Firebrowse - Broad ]
    SOURCE (Princeton)Expression in : [Datasets]   [Normal Tissue Atlas]  [carcinoma Classsification]  [NCI60]
    GenevisibleExpression in : [tissues]  [cell-lines]  [cancer]  [perturbations]  
    BioGPS (Tissue expression)324
    GTEX Portal (Tissue expression)APC
    Protein : pattern, domain, 3D structure
    UniProt/SwissProtP25054   [function]  [subcellular_location]  [family_and_domains]  [pathology_and_biotech]  [ptm_processing]  [expression]  [interaction]
    NextProtP25054  [Sequence]  [Exons]  [Medical]  [Publications]
    With graphics : InterProP25054
    Splice isoforms : SwissVarP25054
    PhosPhoSitePlusP25054
    Domaine pattern : Prosite (Expaxy)ARM_REPEAT (PS50176)   
    Domains : Interpro (EBI)APC    APC_15aa_rpt    APC_basic_dom    APC_dom    Apc_fam    APC_N    APC_rpt    ARM-like    ARM-type_fold    Armadillo    EB1-bd    SAMP   
    Domain families : Pfam (Sanger)APC_15aa (PF05972)    APC_basic (PF05956)    APC_crr (PF05923)    APC_N_CC (PF16689)    Arm (PF00514)    EB1_binding (PF05937)    SAMP (PF05924)   
    Domain families : Pfam (NCBI)pfam05972    pfam05956    pfam05923    pfam16689    pfam00514    pfam05937    pfam05924   
    Domain families : Smart (EMBL)ARM (SM00185)  
    Conserved Domain (NCBI)APC
    DMDM Disease mutations324
    Blocks (Seattle)APC
    PDB (SRS)1DEB    1EMU    1JPP    1M5I    1T08    1TH1    1V18    2RQU    3AU3    3NMW    3NMX    3NMZ    3QHE    3RL7    3RL8    3T7U    4G69   
    PDB (PDBSum)1DEB    1EMU    1JPP    1M5I    1T08    1TH1    1V18    2RQU    3AU3    3NMW    3NMX    3NMZ    3QHE    3RL7    3RL8    3T7U    4G69   
    PDB (IMB)1DEB    1EMU    1JPP    1M5I    1T08    1TH1    1V18    2RQU    3AU3    3NMW    3NMX    3NMZ    3QHE    3RL7    3RL8    3T7U    4G69   
    PDB (RSDB)1DEB    1EMU    1JPP    1M5I    1T08    1TH1    1V18    2RQU    3AU3    3NMW    3NMX    3NMZ    3QHE    3RL7    3RL8    3T7U    4G69   
    Structural Biology KnowledgeBase1DEB    1EMU    1JPP    1M5I    1T08    1TH1    1V18    2RQU    3AU3    3NMW    3NMX    3NMZ    3QHE    3RL7    3RL8    3T7U    4G69   
    SCOP (Structural Classification of Proteins)1DEB    1EMU    1JPP    1M5I    1T08    1TH1    1V18    2RQU    3AU3    3NMW    3NMX    3NMZ    3QHE    3RL7    3RL8    3T7U    4G69   
    CATH (Classification of proteins structures)1DEB    1EMU    1JPP    1M5I    1T08    1TH1    1V18    2RQU    3AU3    3NMW    3NMX    3NMZ    3QHE    3RL7    3RL8    3T7U    4G69   
    SuperfamilyP25054
    Human Protein AtlasENSG00000134982
    Peptide AtlasP25054
    HPRD01439
    IPIIPI00012391   IPI00215877   IPI00974301   IPI00930146   IPI00967278   IPI00979931   IPI00967116   IPI00964920   
    Protein Interaction databases
    DIP (DOE-UCLA)P25054
    IntAct (EBI)P25054
    FunCoupENSG00000134982
    BioGRIDAPC
    STRING (EMBL)APC
    ZODIACAPC
    Ontologies - Pathways
    QuickGOP25054
    Ontology : AmiGOmitotic cytokinesis  kinetochore  cell fate specification  protein binding  nucleus  nucleoplasm  cytoplasm  centrosome  cytosol  cytoplasmic microtubule  plasma membrane  plasma membrane  cell-cell adherens junction  bicellular tight junction  cell cortex  protein complex assembly  cellular component disassembly involved in execution phase of apoptosis  cellular response to DNA damage stimulus  negative regulation of microtubule depolymerization  negative regulation of microtubule depolymerization  cell cycle arrest  mitotic spindle assembly checkpoint  cell adhesion  establishment or maintenance of cell polarity  pattern specification process  beta-catenin binding  microtubule binding  negative regulation of cell proliferation  Wnt signaling pathway  lateral plasma membrane  catenin complex  cell migration  protein kinase regulator activity  protein kinase binding  lamellipodium  positive regulation of cell migration  dendrite  beta-catenin destruction complex  pancreas development  neuron projection development  positive regulation of pseudopodium assembly  nuclear membrane  ruffle membrane  regulation of microtubule-based process  response to drug  neuronal cell body  positive regulation of apoptotic process  proteasome-mediated ubiquitin-dependent protein catabolic process  axonal growth cone  neuron projection terminus  synapse  gamma-catenin binding  cadherin binding  regulation of cell differentiation  positive regulation of protein catabolic process  positive regulation of protein catabolic process  negative regulation of cyclin-dependent protein serine/threonine kinase activity  microtubule plus-end binding  regulation of attachment of spindle microtubules to kinetochore  regulation of attachment of spindle microtubules to kinetochore  canonical Wnt signaling pathway  canonical Wnt signaling pathway  bicellular tight junction assembly  cell body fiber  negative regulation of canonical Wnt signaling pathway  response to alcohol  beta-catenin destruction complex assembly  beta-catenin destruction complex disassembly  cellular response to nerve growth factor stimulus  Wnt signalosome  regulation of glutamate metabolic process  
    Ontology : EGO-EBImitotic cytokinesis  kinetochore  cell fate specification  protein binding  nucleus  nucleoplasm  cytoplasm  centrosome  cytosol  cytoplasmic microtubule  plasma membrane  plasma membrane  cell-cell adherens junction  bicellular tight junction  cell cortex  protein complex assembly  cellular component disassembly involved in execution phase of apoptosis  cellular response to DNA damage stimulus  negative regulation of microtubule depolymerization  negative regulation of microtubule depolymerization  cell cycle arrest  mitotic spindle assembly checkpoint  cell adhesion  establishment or maintenance of cell polarity  pattern specification process  beta-catenin binding  microtubule binding  negative regulation of cell proliferation  Wnt signaling pathway  lateral plasma membrane  catenin complex  cell migration  protein kinase regulator activity  protein kinase binding  lamellipodium  positive regulation of cell migration  dendrite  beta-catenin destruction complex  pancreas development  neuron projection development  positive regulation of pseudopodium assembly  nuclear membrane  ruffle membrane  regulation of microtubule-based process  response to drug  neuronal cell body  positive regulation of apoptotic process  proteasome-mediated ubiquitin-dependent protein catabolic process  axonal growth cone  neuron projection terminus  synapse  gamma-catenin binding  cadherin binding  regulation of cell differentiation  positive regulation of protein catabolic process  positive regulation of protein catabolic process  negative regulation of cyclin-dependent protein serine/threonine kinase activity  microtubule plus-end binding  regulation of attachment of spindle microtubules to kinetochore  regulation of attachment of spindle microtubules to kinetochore  canonical Wnt signaling pathway  canonical Wnt signaling pathway  bicellular tight junction assembly  cell body fiber  negative regulation of canonical Wnt signaling pathway  response to alcohol  beta-catenin destruction complex assembly  beta-catenin destruction complex disassembly  cellular response to nerve growth factor stimulus  Wnt signalosome  regulation of glutamate metabolic process  
    Pathways : BIOCARTATGF beta signaling pathway [Genes]    Inactivation of Gsk3 by AKT causes accumulation of b-catenin in Alveolar Macrophages [Genes]    Presenilin action in Notch and Wnt signaling [Genes]    ALK in cardiac myocytes [Genes]    Multi-step Regulation of Transcription by Pitx2 [Genes]    WNT Signaling Pathway [Genes]   
    Pathways : KEGGWnt signaling pathway    Hippo signaling pathway    Regulation of actin cytoskeleton    HTLV-I infection    Pathways in cancer    MicroRNAs in cancer    Colorectal cancer    Endometrial cancer    Basal cell carcinoma   
    REACTOMEP25054 [protein]
    REACTOME Pathways111465 [pathway]   195253 [pathway]   196299 [pathway]   3769402 [pathway]   4641262 [pathway]   5339716 [pathway]   5358747 [pathway]   5358749 [pathway]   5358751 [pathway]   5358752 [pathway]   5467333 [pathway]   5467337 [pathway]   5467340 [pathway]   5467348 [pathway]   5689896 [pathway]   
    NDEx NetworkAPC
    Atlas of Cancer Signalling NetworkAPC
    Wikipedia pathwaysAPC
    Orthology - Evolution
    OrthoDB324
    GeneTree (enSembl)ENSG00000134982
    Phylogenetic Trees/Animal Genes : TreeFamAPC
    HOVERGENP25054
    HOGENOMP25054
    Homologs : HomoloGeneAPC
    Homology/Alignments : Family Browser (UCSC)APC
    Gene fusions - Rearrangements
    Fusion : MitelmanAPC/ALDH1L1 [5q22.2/3q21.3]  
    Fusion : MitelmanAPC/KRT6A [5q22.2/12q13.13]  [t(5;12)(q22;q13)]  
    Fusion: TCGAAPC 5q22.2 ALDH1L1 3q21.3 KIRC
    Polymorphisms : SNP and Copy number variants
    NCBI Variation ViewerAPC [hg38]
    dbSNP Single Nucleotide Polymorphism (NCBI)APC
    dbVarAPC
    ClinVarAPC
    1000_GenomesAPC 
    Exome Variant ServerAPC
    ExAC (Exome Aggregation Consortium)APC (select the gene name)
    Genetic variants : HAPMAP324
    Genomic Variants (DGV)APC [DGVbeta]
    DECIPHER (Syndromes)5:112073556-112181936  ENSG00000134982
    CONAN: Copy Number AnalysisAPC 
    Mutations
    ICGC Data PortalAPC 
    TCGA Data PortalAPC 
    Broad Tumor PortalAPC
    OASIS PortalAPC [ Somatic mutations - Copy number]
    Cancer Gene: CensusAPC 
    Somatic Mutations in Cancer : COSMICAPC  [overview]  [genome browser]  [tissue]  [distribution]  
    Mutations and Diseases : HGMDAPC
    intOGen PortalAPC
    LOVD (Leiden Open Variation Database)Whole genome datasets
    LOVD (Leiden Open Variation Database)LOVD - Leiden Open Variation Database
    LOVD (Leiden Open Variation Database)LOVD 3.0 shared installation
    LOVD (Leiden Open Variation Database)Zhejiang University Center for Genetic and Genomic Medicine (ZJU-CGGM)
    LOVD (Leiden Open Variation Database)SpainMDB
    BioMutasearch APC
    DgiDB (Drug Gene Interaction Database)APC
    DoCM (Curated mutations)APC (select the gene name)
    CIViC (Clinical Interpretations of Variants in Cancer)APC (select a term)
    intoGenAPC
    NCG5 (London)APC
    Cancer3DAPC(select the gene name)
    Impact of mutations[PolyPhen2] [SIFT Human Coding SNP] [Buck Institute : MutDB] [Mutation Assessor] [Mutanalyser]
    Diseases
    OMIM114500    114550    135290    175100    175100    611731    613659   
    Orphanet19550    19893    2913    21470    8665    11544    14391   
    MedgenAPC
    Genetic Testing Registry APC
    NextProtP25054 [Medical]
    TSGene324
    GENETestsAPC
    Huge Navigator APC [HugePedia]
    snp3D : Map Gene to Disease324
    BioCentury BCIQAPC
    ClinGenAPC (curated)
    Clinical trials, drugs, therapy
    Chemical/Protein Interactions : CTD324
    Chemical/Pharm GKB GenePA24875
    Drug Sensitivity APC
    Clinical trialAPC
    Miscellaneous
    canSAR (ICR)APC (select the gene name)
    Other databaseUMD-APC (adenomatosis polyposis coli). Curators: C. Béroud and T. Soussi
    Other databaseAPC (Broad)
    Probes
    Litterature
    PubMed499 Pubmed reference(s) in Entrez
    GeneRIFsGene References Into Functions (Entrez)
    CoreMineAPC
    EVEXAPC
    GoPubMedAPC
    iHOPAPC
    REVIEW articlesautomatic search in PubMed
    Last year publicationsautomatic search in PubMed

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    indexed on : Tue Mar 14 13:36:15 CET 2017

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