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PDGFB platelet-derived growth factor beta polypeptide (simian sarcoma viral (v-sis) oncogene homolog)

Written2001-02Marie-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

(Note : for Links provided by Atlas : click)

Identity

Other aliasV-sis platelet-derived growth factor beta (simian sarcoma viral oncogene homolog)
LocusID (NCBI) 5155
Atlas_Id 155
Location 22q13.1  [Link to chromosome band 22q13]
Location_base_pair Starts at and ends at bp from pter
Local_order Telomeric to TXN2 (thioredoxin, mitochondrial), centromeric to DMC1(dosage suppressor of mck1, yeast homologue meiosis-specific homologous recombination)
Fusion genes
(updated 2017)
Data from Atlas, Mitelman, Cosmic Fusion, Fusion Cancer, TCGA fusion databases with official HUGO symbols (see references in chromosomal bands)
COL1A1 (17q21.33) / PDGFB (22q13.1)IQGAP2 (5q13.3) / PDGFB (22q13.1)PDGFB (22q13.1) / COL1A1 (17q21.33)

DNA/RNA

 
Description The PDGFB gene encodes the human platelet-derived growth factor (PDGF) B chain precursor and is the cellular homologue of the v-sis oncogene. PDGFB gene is 22 kb in size and is composed of 7 exons. The exon 7 and most part of the exon 1 are non coding sequences (white boxes).
Transcription The PDGFB chain precursor is usually translated from a 3.5 kb transcript. The first exon contains the sequence for the signal peptide preceeded by a 1 kb-long untranslated sequence with potent translation inhibitory activity. A 2.6 kb mRNA which initiates at an alternative exon 1, exon 1A, was described in the human choriocarcinoma cell line JEG-3. It initiates an open reading frame that is continuous with the code for the PDGF B chain precursor but lacks the code for the signal peptide.

Protein

 
Description The PDGFB chains are synthesised as 240 amino acids precursors molecules containing amino and carboxy-terminal propeptides, which are removed by site-specific endopeptidases. Two PDGFB precursor chains associate in dimers to form the mature PDGFBB after proteolysis.
Expression First isolated from human platelets, the PDGFBB is synthesized by a variety of different cell lineages.
Localisation Secreted in the extra-cellular medium
Function The homodimer PDGFBB is a potent growth factor that acts as a mitogen and chemo-attractant for a variety of cells from mesenchymal origin. It has various roles in embryonic development, tissue regeneration, osteogenesis, fibrosis, atherosclerosis, and neoplasia.
Homology Member of the PDGF/VEGF family

Implicated in

Note
  
Entity
  • Dermatofibrosarcoma Protuberans (DP), also called Darier Ferrand tumour or Darier-Hoffmann tumour.
  •   
    Entity
  • Giant cell fibrosarcoma (GCF) (juvenile form of DP).
  •   
    Entity
  • 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

     

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    The American journal of surgical pathology. 1998 ; 22 (5) : 576-587.
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    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.
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    Translocation, t(17;22)(q22;q13), in dermatofibrosarcoma protuberans: a new tumor-associated chromosome rearrangement.
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    Citation

    This paper should be referenced as such :
    Simon, MP ; Maire, G ; Pedeutour, F
    PDGFB (platelet-derived growth factor beta polypeptide (simian sarcoma viral (v-sis) oncogene homolog))
    Atlas Genet Cytogenet Oncol Haematol. 2001;5(2):93-97.
    Free journal version : [ pdf ]   [ DOI ]
    On line version : http://AtlasGeneticsOncology.org/Genes/PDGFBID155.html


    Other Leukemias implicated (Data extracted from papers in the Atlas) [ 10 ]
      t(17;22)(q21;q13) COL1A1/PDGFB
    t(1;5)(q21;q32) PDE4DIP/PDGFRB::t(1;5)(q21-23;q32) TPM3/PDGFRB::t(1;5)(q21-23;q31-33)
    t(2;5)(p21;q33) SPTBN1/PDGFRB
    t(5;11)(q33;p13) CAPRIN1/PDGFRB
    t(5;11)(q33;q13) NUMA1/PDGFRB a novel fusion
    t(5;12)(q33;q24) GIT2/PDGFRB
    t(5;14)(q33;q32) PDGFRB/CCDC88C
    t(5;15)(q33;q22) TP53BP1/PDGFRB
    t(5;16)(q32;p13) NDE1/PDGFRB
    t(17;22)(q21;q13) COL1A1/PDGFB


    Other Solid tumors implicated (Data extracted from papers in the Atlas) [ 4 ]
      Soft Tissues: Dermatofibrosarcoma Protuberans
    Bone: Osteoid Osteoma
    Soft tissue tumors: an overview
    t(17;22)(q22;q13) COL1A1/PDGFB


    External links

    Nomenclature
    Cards
    AtlasPDGFBID155.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)5155
    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)
    Probes
    Litterature
    REVIEW articlesautomatic search in PubMed
    Last year publicationsautomatic search in PubMed


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    indexed on : Thu Oct 18 17:47:03 CEST 2018

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