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COL1A1 (collagen, type I, alpha 1)

Identity

HGNC (Hugo) COL1A1
LocusID (NCBI) 1277
Location 17q21.33
Location_base_pair Starts at 48261457 and ends at 48279000 bp from pter ( according to hg19-Feb_2009)  [Mapping]
Local_order Telomeric to MEOX1 (mesenchyme homeo box 1), centromeric to MVWF (Modifier of von Willebrand factor)
 
  COL1A1 (17q21) - Courtesy Mariano Rocchi, Resources for Molecular Cytogenetics.

DNA/RNA

 
Description The COL1A1 gene is 18 kb in size and is composed of 52 exons. Exons 6 to 49 encode the alpha helical domain. Most of these exons were 45 bp, 54 bp or multiple of 45 bp or 54 bp
Transcription Two RNA of 5,8 kb and 4,8 kb differing by their ‘3 terminus non coding sequence and giving rise to a single 140 kDa protein

Protein

 
Description 1464 amino acids. The a1 (I) chains of the type I collagen are synthesised as procollagen molecules containing amino and carboxy-terminal propeptides, wich are removed by site-specific endopeptidase. The central triple helical domain is formed by 338 repeats of a Gly-X-Y triplet where X and Y are often a proline.
Expression Type I collagen is the most abundant protein in vertebrates and a constituent of the extra cellular matrix in connective tissue of bone, skin, tendon, ligament and dentine. It is mostly produced and secreted by fibroblasts and osteoblasts.
Localisation Extra-cellular matrix
Function Two pro a1 (I) chain associate in trimers with one pro a2 (I) chain to form the type I collagen fibrils after proteolysis.
Homology Member of the collagen family.

Implicated in

Entity
  • Dermatofibrosarcoma Protuberans (DP), also called Darier Ferrand tumour or Darier-Hoffmann tumour.
  • Giant cell fibrosarcoma (GCF) (juvenile form of DP).
  • Bednar tumour (pigmented variant of DP)
  • Disease Infiltrative skin tumours of intermediate malignancy
    Prognosis The prognosis is usually favourable. These tumours are locally aggressive and highly recurrent, but metastases or tumour-related deaths are extremely rare.
    Cytogenetics Dermatofibrosarcoma Protuberans, Giant Cell fibrosarcoma and Bednar tumours present specific cytogenetic features such as reciprocal translocations t(17;22)(q22;q13.1) ( Fig A) or, more often, supernumerary ring chromosomes derived from t(17;22) (B). As shown by FISH analysis, the ring chromosomes contain chromosome 22 centromere and low-level amplification of 22cen-q13.1 and 17q22-qter sequences. To note, in most cases, the derivative chromosome 17 is not present. In contrast, several copies of the derivative chromosome 22 are generally observed.in addition to two apparently normal chromosomes 17
     
    Hybrid/Mutated Gene
  • Both rings and der(22) translocated chromosomes present a same molecular rearrangement that fuses the collagen type I alpha 1(COL1A1) and the platelet-derived growth factor B chain (PDGFB) genes (C).
  • In all DP and GCF cases studied, the t(17;22)translocation results in chimerical COL1A1/PDGFB mRNA production, in which the PDGFB exon 1 is deleted and replaced by a variable segment of COL1A1 mRNA sequence. In the 32 cases tested the fusion mRNA was an in-frame fusion of one of the COL1A1 exons (varying from exon 7 to exon 47) to PDGFB exon 2 (D).
  • Abnormal Protein
  • COL1A1 and PDGFB are both encoded as pro-peptides, which are processed by proteolytic cleavage at N and C-terminus, to give mature proteins. Sequences analyses of the chimerical COL1A1/PDGFB fusion transcripts showed that the COL1A1/PDGFB putative proteins displayed a pro-peptide structure, which preserved the N-terminus COL1A1 pro-peptide containing the signal peptide and the N and C-terminus PDGFB maturation cleavage sites.
  • The functional and structural properties of the COL1A1/PDGFB fusion protein were characterized by generating stable fibroblastic cell lines that expressed tumour-derived COL1A1/PDGFB chimerical genes. The diagram herein given presents the COL1A1/PDGFB chimerical protein encoded by the T94796 tumour-derived chimerical COL1A1/PDGFB cDNA sequence
  •  
    A chimerical COL1A1/PDGFB cDNA sequence fusing COL1A1 exon 29 to PDGFB exon 2 was isolated from the DP T94796 tumour and stably transfected in the Chinese hamster lung fibroblastic cell line PS200 (E).
    The T94796 COL1A1/PDGFB chimerical protein sequence retained the COL1A1 N-terminus processing site encoded by the COL1A1 exon 6 and the N and C-terminus PDGFB processing sites encoded by the PDGFB exons 3 and 6 respectively (F).
    Mutagenesis experiments and immunodetection with anti-PDGFBB and specific anti-COL1A1/PDGFB antibodies showed that COL1A1/PDGFB expressing cells produced 116 kD chimerical COL1A1/PDGFB precursors chains, which formed dimers and were processed to give active 30 kD PDGFB-like dimers (G).
    Oncogenesis
  • Transfected cells lines expressing the chimerical T94796-COL1A1/PDGFB proteins became independent upon growth factors, including PDGFB, and induced tumours formation in nude mice. In addition, it was shown that the COL1A1/PDGFB stable clones cells contained activated PDGF b-receptors and that the conditioned media from COL1A1/PDGFB transfected cells were able to stimulate fibroblastic cells growth. Anti-PDGFBB antibodies neutralized this effect.
  • These results strongly suggest that the COL1A1/PDGFB chimerical gene expression associated with DP, contributes to tumour formation through ectopic production of mature PDGFB and the formation of an autocrine loop.
  •   

    Breakpoints

     
     

    Other Solid tumors implicated (Data extracted from papers in the Atlas)

    Solid Tumors AmeloblastomID5945 MedulloblastomaID5065 rhab5004 rhabID5004

    External links

    Nomenclature
    HGNC (Hugo)COL1A1   2197
    Cards
    AtlasCOL1A1ID186
    Entrez_Gene (NCBI)COL1A1  1277  collagen, type I, alpha 1
    GeneCards (Weizmann)COL1A1
    Ensembl hg19 (Hinxton)ENSG00000108821 [Gene_View]  chr17:48261457-48279000 [Contig_View]  COL1A1 [Vega]
    Ensembl hg38 (Hinxton)ENSG00000108821 [Gene_View]  chr17:48261457-48279000 [Contig_View]  COL1A1 [Vega]
    ICGC DataPortalENSG00000108821
    cBioPortalCOL1A1
    AceView (NCBI)COL1A1
    Genatlas (Paris)COL1A1
    WikiGenes1277
    SOURCE (Princeton)COL1A1
    Genomic and cartography
    GoldenPath hg19 (UCSC)COL1A1  -     chr17:48261457-48279000 -  17q21.33   [Description]    (hg19-Feb_2009)
    GoldenPath hg38 (UCSC)COL1A1  -     17q21.33   [Description]    (hg38-Dec_2013)
    EnsemblCOL1A1 - 17q21.33 [CytoView hg19]  COL1A1 - 17q21.33 [CytoView hg38]
    Mapping of homologs : NCBICOL1A1 [Mapview hg19]  COL1A1 [Mapview hg38]
    OMIM114000   120150   130000   130060   166200   166210   166220   166710   259420   
    Gene and transcription
    Genbank (Entrez)AB209597 AK297731 BC036531 DQ893571 EU176569
    RefSeq transcript (Entrez)NM_000088
    RefSeq genomic (Entrez)AC_000149 NC_000017 NC_018928 NG_007400 NT_010783 NW_001838448 NW_004929407
    Consensus coding sequences : CCDS (NCBI)COL1A1
    Cluster EST : UnigeneHs.681002 [ NCBI ]
    CGAP (NCI)Hs.681002
    Alternative Splicing : Fast-db (Paris)GSHG0013562
    Alternative Splicing GalleryENSG00000108821
    Gene ExpressionCOL1A1 [ NCBI-GEO ]     COL1A1 [ SEEK ]   COL1A1 [ MEM ]
    SOURCE (Princeton)Expression in : [Normal Tissue Atlas]  [carcinoma Classsification]  [NCI60]
    Protein : pattern, domain, 3D structure
    UniProt/SwissProtP02452 (Uniprot)
    NextProtP02452  [Medical]
    With graphics : InterProP02452
    Splice isoforms : SwissVarP02452 (Swissvar)
    Domaine pattern : Prosite (Expaxy)NC1_FIB (PS51461)    VWFC_1 (PS01208)    VWFC_2 (PS50184)   
    Domains : Interpro (EBI)Collagen    Fib_collagen_C    VWF_C   
    Related proteins : CluSTrP02452
    Domain families : Pfam (Sanger)COLFI (PF01410)    Collagen (PF01391)    VWC (PF00093)   
    Domain families : Pfam (NCBI)pfam01410    pfam01391    pfam00093   
    Domain families : Smart (EMBL)COLFI (SM00038)  VWC (SM00214)  
    Domain structure : Prodom (Prabi Lyon)Fib_collagen_C (PD002078)   
    DMDM Disease mutations1277
    Blocks (Seattle)P02452
    PDB (SRS)1Q7D    2LLP    3EJH    3GXE   
    PDB (PDBSum)1Q7D    2LLP    3EJH    3GXE   
    PDB (IMB)1Q7D    2LLP    3EJH    3GXE   
    PDB (RSDB)1Q7D    2LLP    3EJH    3GXE   
    Human Protein AtlasENSG00000108821
    Peptide AtlasP02452
    HPRD00362
    IPIIPI00297646   
    Protein Interaction databases
    DIP (DOE-UCLA)P02452
    IntAct (EBI)P02452
    FunCoupENSG00000108821
    BioGRIDCOL1A1
    IntegromeDBCOL1A1
    STRING (EMBL)COL1A1
    Ontologies - Pathways
    QuickGOP02452
    Ontology : AmiGOskeletal system development  blood vessel development  osteoblast differentiation  intramembranous ossification  endochondral ossification  extracellular matrix structural constituent  protein binding  extracellular region  collagen type I trimer  extracellular space  endoplasmic reticulum lumen  response to nutrient  blood coagulation  visual perception  sensory perception of sound  positive regulation of epithelial to mesenchymal transition  negative regulation of cell-substrate adhesion  protein transport  extracellular matrix disassembly  platelet activation  extracellular matrix organization  collagen fibril organization  positive regulation of cell migration  collagen catabolic process  extracellular matrix  extracellular matrix  response to corticosteroid  response to estradiol  collagen biosynthetic process  protein localization to nucleus  tooth mineralization  response to hydrogen peroxide  identical protein binding  response to peptide hormone  skin morphogenesis  positive regulation of transcription, DNA-templated  metal ion binding  platelet-derived growth factor binding  embryonic skeletal system development  leukocyte migration  response to cAMP  face morphogenesis  bone trabecula formation  cartilage development involved in endochondral bone morphogenesis  protein heterotrimerization  cellular response to amino acid stimulus  cellular response to mechanical stimulus  cellular response to retinoic acid  cellular response to transforming growth factor beta stimulus  positive regulation of canonical Wnt signaling pathway  
    Ontology : EGO-EBIskeletal system development  blood vessel development  osteoblast differentiation  intramembranous ossification  endochondral ossification  extracellular matrix structural constituent  protein binding  extracellular region  collagen type I trimer  extracellular space  endoplasmic reticulum lumen  response to nutrient  blood coagulation  visual perception  sensory perception of sound  positive regulation of epithelial to mesenchymal transition  negative regulation of cell-substrate adhesion  protein transport  extracellular matrix disassembly  platelet activation  extracellular matrix organization  collagen fibril organization  positive regulation of cell migration  collagen catabolic process  extracellular matrix  extracellular matrix  response to corticosteroid  response to estradiol  collagen biosynthetic process  protein localization to nucleus  tooth mineralization  response to hydrogen peroxide  identical protein binding  response to peptide hormone  skin morphogenesis  positive regulation of transcription, DNA-templated  metal ion binding  platelet-derived growth factor binding  embryonic skeletal system development  leukocyte migration  response to cAMP  face morphogenesis  bone trabecula formation  cartilage development involved in endochondral bone morphogenesis  protein heterotrimerization  cellular response to amino acid stimulus  cellular response to mechanical stimulus  cellular response to retinoic acid  cellular response to transforming growth factor beta stimulus  positive regulation of canonical Wnt signaling pathway  
    Pathways : KEGGPI3K-Akt signaling pathway    Focal adhesion    ECM-receptor interaction    Protein digestion and absorption    Amoebiasis   
    REACTOMEP02452 [protein]
    REACTOME PathwaysREACT_160300 Binding and Uptake of Ligands by Scavenger Receptors [pathway]
    REACTOME PathwaysREACT_118779 Extracellular matrix organization [pathway]
    REACTOME PathwaysREACT_604 Hemostasis [pathway]
    Protein Interaction DatabaseCOL1A1
    DoCM (Curated mutations)COL1A1
    Wikipedia pathwaysCOL1A1
    Gene fusion - rearrangements
    Rearrangement : COSMICCOL1A1 [17q21.33]  -  USP6 [17p13.2]
    Rearrangement : TICdbCOL1A1 [17q21.33]  -  PDGFB [13q12.2]
    Rearrangement : TICdbCOL1A1 [17q21.33]  -  USP6 [4p16.3]
    Polymorphisms : SNP, variants
    NCBI Variation ViewerCOL1A1 [hg38]
    dbSNP Single Nucleotide Polymorphism (NCBI)COL1A1
    dbVarCOL1A1
    ClinVarCOL1A1
    1000_GenomesCOL1A1 
    Exome Variant ServerCOL1A1
    SNP (GeneSNP Utah)COL1A1
    SNP : HGBaseCOL1A1
    Genetic variants : HAPMAPCOL1A1
    Genomic VariantsCOL1A1  COL1A1 [DGVbeta]
    Mutations
    ICGC Data PortalENSG00000108821 
    Cancer Gene: CensusCOL1A1 
    Somatic Mutations in Cancer : COSMICCOL1A1 
    CONAN: Copy Number AnalysisCOL1A1 
    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)Osteogenesis Imperfecta Variant Database
    Impact of mutations[PolyPhen2] [SIFT Human Coding SNP] [Buck Institute : MutDB] [Mutation Assessor] 
    Diseases
    DECIPHER (Syndromes)17:48261457-48279000
    Mutations and Diseases : HGMDCOL1A1
    OMIM114000    120150    130000    130060    166200    166210    166220    166710    259420   
    MedgenCOL1A1
    NextProtP02452 [Medical]
    GENETestsCOL1A1
    Disease Genetic AssociationCOL1A1
    Huge Navigator COL1A1 [HugePedia]  COL1A1 [HugeCancerGEM]
    snp3D : Map Gene to Disease1277
    DGIdb (Drug Gene Interaction db)COL1A1
    General knowledge
    Homologs : HomoloGeneCOL1A1
    Homology/Alignments : Family Browser (UCSC)COL1A1
    Phylogenetic Trees/Animal Genes : TreeFamCOL1A1
    Chemical/Protein Interactions : CTD1277
    Chemical/Pharm GKB GenePA35041
    Clinical trialCOL1A1
    Cancer Resource (Charite)ENSG00000108821
    Other databases
    Probes
    ProbeCancer Cytogenetics (Bari)
    Litterature
    PubMed499 Pubmed reference(s) in Entrez
    CoreMineCOL1A1
    GoPubMedCOL1A1
    iHOPCOL1A1

    Bibliography

    Brittle bones--fragile molecules: disorders of collagen gene structure and expression.
    Byers PH
    Trends in genetics : TIG. 1990 ; 6 (9) : 293-300.
    PMID 2238087
     
    Ring 22 chromosomes in dermatofibrosarcoma protuberans are low-level amplifiers of chromosome 17 and 22 sequences.
    Pedeutour F, Simon MP, Minoletti F, Sozzi G, Pierotti MA, Hecht F, Turc-Carel C
    Cancer research. 1995 ; 55 (11) : 2400-2403.
    PMID 7757993
     
    Soft tissue sarcomas in dermatology.
    Fish FS
    Dermatologic surgery : official publication for American Society for Dermatologic Surgery [et al.]. 1996 ; 22 (3) : 268-273.
    PMID 8599739
     
    Translocation, t(17;22)(q22;q13), in dermatofibrosarcoma protuberans: a new tumor-associated chromosome rearrangement.
    Pedeutour F, Simon MP, Minoletti F, Barcelo G, Terrier-Lacombe MJ, Combemale P, Sozzi G, Ayraud N, Turc-Carel C
    Cytogenetics and cell genetics. 1996 ; 72 (2-3) : 171-174.
    PMID 8978765
     
    The human type I collagen mutation database.
    Dalgleish R
    Nucleic acids research. 1997 ; 25 (1) : 181-187.
    PMID 9016532
     
    Deregulation of the platelet-derived growth factor B-chain gene via fusion with collagen gene COL1A1 in dermatofibrosarcoma protuberans and giant-cell fibroblastoma.
    Simon MP, Pedeutour F, Sirvent N, Grosgeorge J, Minoletti F, Coindre JM, Terrier-Lacombe MJ, Mandahl N, Craver RD, Blin N, Sozzi G, Turc-Carel C, O'Brien KP, Kedra D, Fransson I, Guilbaud C, Dumanski JP
    Nature genetics. 1997 ; 15 (1) : 95-98.
    PMID 8988177
     
    Transforming activity of the chimeric sequence formed by the fusion of collagen gene COL1A1 and the platelet derived growth factor b-chain gene in dermatofibrosarcoma protuberans.
    Greco A, Fusetti L, Villa R, Sozzi G, Minoletti F, Mauri P, Pierotti MA
    Oncogene. 1998 ; 17 (10) : 1313-1319.
    PMID 9771975
     
    Fibrosarcomatous (high-grade) dermatofibrosarcoma protuberans: clinicopathologic and immunohistochemical study of a series of 41 cases with emphasis on prognostic significance.
    Mentzel T, Beham A, Katenkamp D, Dei Tos AP, Fletcher CD
    The American journal of surgical pathology. 1998 ; 22 (5) : 576-587.
    PMID 9591728
     
    COL1A1-PDGFB fusion in a ring chromosome 4 found in a dermatofibrosarcoma protuberans.
    Navarro M, Simon MP, Migeon C, Turc-Carel C, Pedeutour F
    Genes, chromosomes & cancer. 1998 ; 23 (3) : 263-266.
    PMID 9790508
     
    Various regions within the alpha-helical domain of the COL1A1 gene are fused to the second exon of the PDGFB gene in dermatofibrosarcomas and giant-cell fibroblastomas.
    O'Brien KP, Seroussi E, Dal Cin P, Sciot R, Mandahl N, Fletcher JA, Turc-Carel C, Dumanski JP
    Genes, chromosomes & cancer. 1998 ; 23 (2) : 187-193.
    PMID 9739023
     
    The dermatofibrosarcoma protuberans-associated collagen type Ialpha1/platelet-derived growth factor (PDGF) B-chain fusion gene generates a transforming protein that is processed to functional PDGF-BB.
    Shimizu A, O'Brien KP, SjąŹblom T, Pietras K, Buchdunger E, Collins VP, Heldin CH, Dumanski JP, Ostman A
    Cancer research. 1999 ; 59 (15) : 3719-3723.
    PMID 10446987
     
    Detection of COL1A1-PDGFB fusion transcripts in dermatofibrosarcoma protuberans by reverse transcription-polymerase chain reaction using archival formalin-fixed, paraffin-embedded tissues.
    Wang J, Hisaoka M, Shimajiri S, Morimitsu Y, Hashimoto H
    Diagnostic molecular pathology : the American journal of surgical pathology, part B. 1999 ; 8 (3) : 113-119.
    PMID 10565681
     
    Supernumerary ring chromosome in a Bednar tumor (pigmented dermatofibrosarcoma protuberans) is composed of interspersed sequences from chromosomes 17 and 22: a fluorescence in situ hybridization and comparative genomic hybridization analysis.
    Nishio J, Iwasaki H, Ishiguro M, Ohjimi Y, Yo S, Isayama T, Naito M, Kikuchi M
    Genes, chromosomes & cancer. 2001 ; 30 (3) : 305-309.
    PMID 11170290
     
    Structural and functional analysis of a chimeric protein COL1A1-PDGFB generated by the translocation t(17;22)(q22;q13.1) in Dermatofibrosarcoma protuberans (DP).
    Simon MP, Navarro M, Roux D, Pouyssą©gur J
    Oncogene. 2001 ; 20 (23) : 2965-2975.
    PMID 11420709
     
    REVIEW articlesautomatic search in PubMed
    Last year publicationsautomatic search in PubMed

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    Contributor(s)

    Written02-2001Marie-Pierre Simon, Georges Maire, Florence Pedeutour
    Laboratoire de Genetique, Hopital de l'Archet, 151 route de Saint Antoine de Ginestiere BP 3079, 06202 Nice Cedex 3, France

    Citation

    This paper should be referenced as such :
    Simon, MP ; Maire, G ; Pedeutour, F
    COL1A1 (collagen, type I, alpha 1)
    Atlas Genet Cytogenet Oncol Haematol. 2001;5(2):78-82.
    Free online version   Free pdf version   [Bibliographic record ]
    URL : http://AtlasGeneticsOncology.org/Genes/COL1A1ID186.html

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    indexed on : Sun Dec 21 03:05:45 CET 2014

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