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PLAG1 (Pleomorphic adenoma gene 1)

Written2002-06David Gisselsson
Department of Clinical Genetics, University Hospital, SE-221 85 Lund, Sweden

(Note : for Links provided by Atlas : click)

Identity

Alias_namespleiomorphic adenoma gene 1
Alias_symbol (synonym)ZNF912
Other alias
HGNC (Hugo) PLAG1
LocusID (NCBI) 5324
Atlas_Id 74
Location 8q12.1  [Link to chromosome band 8q12]
Location_base_pair Starts at 56160909 and ends at 56211300 bp from pter ( according to hg19-Feb_2009)  [Mapping PLAG1.png]
Local_order (316 cR / 86 Mb from 8pter)
Fusion genes
(updated 2016)		CHCHD7 (8q12.1) / PLAG1 (8q12.1)COL1A2 (7q21.3) / PLAG1 (8q12.1)COL3A1 (2q32.2) / PLAG1 (8q12.1)
CTNNB1 (3p22.1) / PLAG1 (8q12.1)FGFR1 (8p11.23) / PLAG1 (8q12.1)HAS2 (8q24.13) / PLAG1 (8q12.1)
LIFR (5p13.1) / PLAG1 (8q12.1)PLAG1 (8q12.1) / CHCHD7 (8q12.1)PLAG1 (8q12.1) / CTNNB1 (3p22.1)
PLAG1 (8q12.1) / HAS2 (8q24.13)PLAG1 (8q12.1) / LIFR (5p13.1)PLAG1 (8q12.1) / RPS4Y1 (Yp11.31)
PLAG1 (8q12.1) / TCEA1 (8q11.23)PLAG1 (8q12.1) / TCEA1P2 ()PLAG1 (8q12.1) / TRBJ2-7 ()
RAB2A (8q12.1) / PLAG1 (8q12.1)RAD51B (14q24.1) / PLAG1 (8q12.1)TCEA1 (8q11.23) / PLAG1 (8q12.1)
TCEA1P2 () / PLAG1 (8q12.1)

DNA/RNA

 
  Schematic view of the gene with approximate sizes of introns (kb) and exons (bp); the coding region (violet) translates into a 500 amino acid product with three functional subunits.
Description 7313 bp, 5 exons, 4 introns
Transcription At least two splicing variants, including and excluding the second exon

Protein

Description 500 amino acids with at least three functional regions : 1. Two N-terminal nuclear localisation signals, 2. Seven canonical zinc-finger domains, 3. A serine rich C-terminus
Expression Heart, placenta, spleen, prostate, testis, ovary, small intestine, several tumours
Localisation Nuclear
Function One of the N-terminal nuclear localisation signals (NLS1) interacts with karyopherin a2, which escorts proteins into the nucleus. Three of the seven Zn-finger domains are responsible for interaction with DNA and PLAG1 specifically activates transcription from its consensus binding site. Potential PLAG1 binding sites have been found in the promoter of IGF2.
Homology Mouse and rat Plag1

Mutations

Somatic Involved in chromosome rearrangements in epithelial and mesenchymal tumours. These are typically complex structural abnormalities, resulting in an exchange of regulatory elements and abnormal expression of PLAG1.

Implicated in

Note
  
Entity Pleomorphic adenoma of the salivary gland
Disease Benign epithelial tumour
Prognosis Recovery after surgical removal
Cytogenetics The most common breakpoints are 3p21, 8q12, and 12q15
Hybrid/Mutated Gene The following translocations have been reported to result in hybrid genes involving PLAG1:
  • t(3;8)(p21;q12): CTNNB1 CTNNB1/PLAG1
  • t(5;8)(p13;q12): LIFR/PLAG1
  • Also, rearrangements between PLAG1 and TCEA1 have been detected in cases with normal karyotypes.
    • Abnormal Protein Fusions occur in the 5' regulatory regions, leading to promoter swapping and activation of PLAG1 expression while preserving coding sequences.
      
      
    Entity Carcinoma ex pleomorphic adenoma
    Disease Malignant epithelial tumour arising from pleomorphic adenoma
    Prognosis 30% five-year survival
    Cytogenetics Complex karyotype including t(3;8)(p23;q12)
    Hybrid/Mutated Gene Intragenic PLAG1 rearrangements demonstrated by fluorescence in situ hybridisation.
      
      
    Entity Lipoblastoma
    Disease Benign fat-forming tumour of childhood
    Prognosis Recovery after surgical removal
    Cytogenetics Structural abnormalities involving 8q11-13
    Hybrid/Mutated Gene The following rearrangements have been reported to result in hybrid genes involving PLAG1:
  • del(8)(q12q24), r(8): HAS2/PLAG1
  • t(7;8)(p22;q13): COL1A2/HAS2
    • Abnormal Protein Fusions occur in the 5' regulatory regions, leading promoter swapping and activation of PLAG1 expression while preserving coding sequences.
      

    Breakpoints

     

    Bibliography

    Conserved mechanism of PLAG1 activation in salivary gland tumors with and without chromosome 8q12 abnormalities: identification of SII as a new fusion partner gene.
    Aström AK, Voz ML, Kas K, Röijer E, Wedell B, Mandahl N, Van de Ven W, Mark J, Stenman G
    Cancer research. 1999 ; 59 (4) : 918-923.
    PMID 10029085
     
    Evidence of involvement of the PLAG1 gene in lipoblastomas.
    Astrom A, D'Amore ES, Sainati L, Panarello C, Morerio C, Mark J, Stenman G
    International journal of oncology. 2000 ; 16 (6) : 1107-1110.
    PMID 10811981
     
    Identification of a karyopherin alpha 2 recognition site in PLAG1, which functions as a nuclear localization signal.
    Braem CV, Kas K, Meyen E, Debiec-Rychter M, Van De Ven WJ, Voz ML
    The Journal of biological chemistry. 2002 ; 277 (22) : 19673-19678.
    PMID 11882654
     
    Histologic localization of PLAG1 (pleomorphic adenoma gene 1) in pleomorphic adenoma of the salivary gland: cytogenetic evidence of common origin of phenotypically diverse cells.
    Debiec-Rychter M, Van Valckenborgh I, Van den Broeck C, Hagemeijer A, Van de Ven WJ, Kas K, Van Damme B, Voz ML
    Laboratory investigation; a journal of technical methods and pathology. 2001 ; 81 (9) : 1289-1297.
    PMID 11555676
     
    Expression of PLAG1 and HMGIC proteins and fusion transcripts in radiation-associated pleomorphic adenomas.
    Enlund F, Nordkvist A, Sahlin P, Mark J, Stenman G
    International journal of oncology. 2002 ; 20 (4) : 713-716.
    PMID 11894114
     
    PLAG1 alterations in lipoblastoma: involvement in varied mesenchymal cell types and evidence for alternative oncogenic mechanisms.
    Gisselsson D, Hibbard MK, Dal Cin P, Sciot R, Hsi BL, Kozakewich HP, Fletcher JA
    The American journal of pathology. 2001 ; 159 (3) : 955-962.
    PMID 11549588
     
    The tumorigenic diversity of the three PLAG family members is associated with different DNA binding capacities.
    Hensen K, Van Valckenborgh IC, Kas K, Van de Ven WJ, Voz ML
    Cancer research. 2002 ; 62 (5) : 1510-1517.
    PMID 11888928
     
    PLAG1 fusion oncogenes in lipoblastoma.
    Hibbard MK, Kozakewich HP, Dal Cin P, Sciot R, Tan X, Xiao S, Fletcher JA
    Cancer research. 2000 ; 60 (17) : 4869-4872.
    PMID 10987300
     
    Characterization of chromosome aberrations in salivary gland tumors by FISH, including multicolor COBRA-FISH.
    Jin C, Martins C, Jin Y, Wiegant J, Wennerberg J, Dictor M, Gisselsson D, Strömbeck B, Fonseca I, Mitelman F, Tanke HJ, Höglund M, Mertens F
    Genes, chromosomes & cancer. 2001 ; 30 (2) : 161-167.
    PMID 11135432
     
    A 2-Mb YAC contig and physical map covering the chromosome 8q12 breakpoint cluster region in pleomorphic adenomas of the salivary glands.
    Kas K, Röijer E, Voz M, Meyen E, Stenman G, Van de Ven WJ
    Genomics. 1997 ; 43 (3) : 349-358.
    PMID 9268638
     
    Transcriptional activation capacity of the novel PLAG family of zinc finger proteins.
    Kas K, Voz ML, Hensen K, Meyen E, Van de Ven WJ
    The Journal of biological chemistry. 1998 ; 273 (36) : 23026-23032.
    PMID 9722527
     
    Pleomorphic adenoma gene 1 is expressed in cultured benign and malignant salivary gland tumor cells.
    Queimado L, Lopes C, Du F, Martins C, Bowcock AM, Soares J, Lovett M
    Laboratory investigation; a journal of technical methods and pathology. 1999 ; 79 (5) : 583-589.
    PMID 10334569
     
    Fluorescence in situ hybridization mapping of breakpoints in pleomorphic adenomas with 8q12-13 abnormalities identifies a subgroup of tumors without PLAG1 involvement.
    Röijer E, Kas K, Behrendt M, Van de Ven W, Stenman G
    Genes, chromosomes & cancer. 1999 ; 24 (1) : 78-82.
    PMID 9892112
     
    Assignment of the rat pleiomorphic adenoma genes (Plag1, Plagl1, Plagl2) by in situ hybridization and radiation hybrid mapping.
    Szpirer C, Kas K, Laes JF, Rivière M, Van Vooren P, Szpirer J
    Cytogenetics and cell genetics. 2001 ; 94 (1-2) : 94-95.
    PMID 11701966
     
    PLAG1, the main translocation target in pleomorphic adenoma of the salivary glands, is a positive regulator of IGF-II.
    Voz ML, Agten NS, Van de Ven WJ, Kas K
    Cancer research. 2000 ; 60 (1) : 106-113.
    PMID 10646861
     
    The recurrent translocation t(5;8)(p13;q12) in pleomorphic adenomas results in upregulation of PLAG1 gene expression under control of the LIFR promoter.
    Voz ML, Aström AK, Kas K, Mark J, Stenman G, Van de Ven WJ
    Oncogene. 1998 ; 16 (11) : 1409-1416.
    PMID 9525740
     
    First insights into the molecular basis of pleomorphic adenomas of the salivary glands.
    Voz ML, Van de Ven WJ, Kas K
    Advances in dental research. 2000 ; 14 : 81-83.
    PMID 11842929
     

    Citation

    This paper should be referenced as such :
    Gisselsson, D
    PLAG1 (pleomorphic adenoma gene 1)
    Atlas Genet Cytogenet Oncol Haematol. 2002;6(4):285-287.
    Free journal version : [ pdf ]   [ DOI ]
    On line version : http://AtlasGeneticsOncology.org/Genes/PLAG1ID74.html

    Other Solid tumors implicated (Data extracted from papers in the Atlas) [ 8 ]
      Soft Tissues: Lipoblastoma
    Head and Neck: Pleomorphic salivary gland adenoma with inv(8)(q12q12) CHCHD7/PLAG1
    Head and Neck: Pleomorphic salivary gland adenoma with ins(8)(q12;q11q11) TCEA1/PLAG1
    Head and Neck: Salivary gland tumors: an overview
    Soft tissue tumors: an overview
    Soft Tissues: Lipoblastoma with t(2;8)(q32;q12.1) COL3A1/PLAG1
    Soft Tissues: Lipoblastoma with t(8;8)(q12;q12) RAB2A/PLAG1
    Vulva and Vagina tumors: an overview

    External links

    Nomenclature
    HGNC (Hugo)PLAG1   9045
    Cards
    AtlasPLAG1ID74
    Entrez_Gene (NCBI)PLAG1  5324  PLAG1 zinc finger
    AliasesPSA; SGPA; ZNF912
    GeneCards (Weizmann)PLAG1
    Ensembl hg19 (Hinxton)ENSG00000181690 [Gene_View]
    Ensembl hg38 (Hinxton)ENSG00000181690 [Gene_View]  chr8:56160909-56211300 [Contig_View]  PLAG1 [Vega]
    ICGC DataPortalENSG00000181690
    TCGA cBioPortalPLAG1
    AceView (NCBI)PLAG1
    Genatlas (Paris)PLAG1
    WikiGenes5324
    SOURCE (Princeton)PLAG1
    Genetics Home Reference (NIH)PLAG1
    Genomic and cartography
    GoldenPath hg38 (UCSC)PLAG1  -     chr8:56160909-56211300 -  8q12.1   [Description]    (hg38-Dec_2013)
    GoldenPath hg19 (UCSC)PLAG1  -     8q12.1   [Description]    (hg19-Feb_2009)
    EnsemblPLAG1 - 8q12.1 [CytoView hg19]  PLAG1 - 8q12.1 [CytoView hg38]
    Mapping of homologs : NCBIPLAG1 [Mapview hg19]  PLAG1 [Mapview hg38]
    OMIM181030   603026   
    Gene and transcription
    Genbank (Entrez)AB209131 AF221549 AF221550 AK296933 AK313663
    RefSeq transcript (Entrez)NM_001114634 NM_001114635 NM_002655
    RefSeq genomic (Entrez)
    Consensus coding sequences : CCDS (NCBI)PLAG1
    Cluster EST : UnigeneHs.14968 [ NCBI ]
    CGAP (NCI)Hs.14968
    Alternative Splicing GalleryENSG00000181690
    Gene ExpressionPLAG1 [ NCBI-GEO ]   PLAG1 [ EBI - ARRAY_EXPRESS ]   PLAG1 [ SEEK ]   PLAG1 [ MEM ]
    Gene Expression Viewer (FireBrowse)PLAG1 [ Firebrowse - Broad ]
    SOURCE (Princeton)Expression in : [Datasets]   [Normal Tissue Atlas]  [carcinoma Classsification]  [NCI60]
    GenevisibleExpression in : [tissues]  [cell-lines]  [cancer]  [perturbations]  
    BioGPS (Tissue expression)5324
    GTEX Portal (Tissue expression)PLAG1
    Protein : pattern, domain, 3D structure
    UniProt/SwissProtQ6DJT9   [function]  [subcellular_location]  [family_and_domains]  [pathology_and_biotech]  [ptm_processing]  [expression]  [interaction]
    NextProtQ6DJT9  [Sequence]  [Exons]  [Medical]  [Publications]
    With graphics : InterProQ6DJT9
    Splice isoforms : SwissVarQ6DJT9
    PhosPhoSitePlusQ6DJT9
    Domaine pattern : Prosite (Expaxy)ZINC_FINGER_C2H2_1 (PS00028)    ZINC_FINGER_C2H2_2 (PS50157)   
    Domains : Interpro (EBI)C2H2_Znf_fam    PLAG1    Znf_C2H2    Znf_C2H2-like    Znf_C2H2/integrase_DNA-bd   
    Domain families : Pfam (Sanger)
    Domain families : Pfam (NCBI)
    Domain families : Smart (EMBL)ZnF_C2H2 (SM00355)  
    Conserved Domain (NCBI)PLAG1
    DMDM Disease mutations5324
    Blocks (Seattle)PLAG1
    SuperfamilyQ6DJT9
    Human Protein AtlasENSG00000181690
    Peptide AtlasQ6DJT9
    HPRD04321
    IPIIPI00787796   IPI00002594   
    Protein Interaction databases
    DIP (DOE-UCLA)Q6DJT9
    IntAct (EBI)Q6DJT9
    FunCoupENSG00000181690
    BioGRIDPLAG1
    STRING (EMBL)PLAG1
    ZODIACPLAG1
    Ontologies - Pathways
    QuickGOQ6DJT9
    Ontology : AmiGORNA polymerase II core promoter proximal region sequence-specific DNA binding  transcriptional activator activity, RNA polymerase II core promoter proximal region sequence-specific binding  transcription factor activity, sequence-specific DNA binding  nucleus  transcription from RNA polymerase II promoter  negative regulation of gene expression  nuclear speck  gland morphogenesis  multicellular organism growth  positive regulation of transcription from RNA polymerase II promoter  metal ion binding  positive regulation of glial cell proliferation  prostate gland growth  
    Ontology : EGO-EBIRNA polymerase II core promoter proximal region sequence-specific DNA binding  transcriptional activator activity, RNA polymerase II core promoter proximal region sequence-specific binding  transcription factor activity, sequence-specific DNA binding  nucleus  transcription from RNA polymerase II promoter  negative regulation of gene expression  nuclear speck  gland morphogenesis  multicellular organism growth  positive regulation of transcription from RNA polymerase II promoter  metal ion binding  positive regulation of glial cell proliferation  prostate gland growth  
    NDEx NetworkPLAG1
    Atlas of Cancer Signalling NetworkPLAG1
    Wikipedia pathwaysPLAG1
    Orthology - Evolution
    OrthoDB5324
    GeneTree (enSembl)ENSG00000181690
    Phylogenetic Trees/Animal Genes : TreeFamPLAG1
    HOVERGENQ6DJT9
    HOGENOMQ6DJT9
    Homologs : HomoloGenePLAG1
    Homology/Alignments : Family Browser (UCSC)PLAG1
    Gene fusions - Rearrangements
    Fusion : MitelmanCOL1A2/PLAG1 [7q21.3/8q12.1]  [t(7;8)(q21;q12)]  
    Fusion : MitelmanCOL3A1/PLAG1 [2q32.2/8q12.1]  [t(2;8)(q32;q12)]  
    Fusion : MitelmanCTNNB1/PLAG1 [3p22.1/8q12.1]  [ins(8;3)(q12;p22p14)]  [t(3;8)(p22;q12)]  
    Fusion : MitelmanFGFR1/PLAG1 [8p11.23/8q12.1]  [r(8)(p11q12)]  
    Fusion : MitelmanHAS2/PLAG1 [8q24.13/8q12.1]  [del(8)(q12q24)]  
    Fusion : MitelmanLIFR/PLAG1 [5p13.1/8q12.1]  [t(5;8)(p13;q12)]  
    Fusion : MitelmanPLAG1/TRBJ2-7 [8q12.1/-]  [t(7;8)(q34;q12)]  
    Fusion : MitelmanRAB2A/PLAG1 [8q12.1/8q12.1]  [t(8;8)(q12;q12)]  
    Fusion : MitelmanRAD51B/PLAG1 [14q24.1/8q12.1]  [t(8;14)(q12;q24)]  
    Fusion : MitelmanTCEA1/PLAG1 [8q11.23/8q12.1]  [t(8;8)(q11;q12)]  
    Fusion : COSMICCHCHD7 [8q12.1]  -  PLAG1 [8q12.1]  [fusion_1087]  [fusion_1088]  [fusion_1089]  
    Fusion : COSMICCOL1A2 [7q21.3]  -  PLAG1 [8q12.1]  [fusion_1097]  [fusion_1098]  [fusion_1099]  
    Fusion : COSMICCTNNB1 [3p22.1]  -  PLAG1 [8q12.1]  [fusion_1077]  [fusion_1078]  [fusion_1079]  [fusion_1080]  
    Fusion : COSMICFGFR1 [8p11.23]  -  PLAG1 [8q12.1]  [fusion_1108]  [fusion_1109]  [fusion_1110]  [fusion_1111]  [fusion_1112]  [fusion_1113]  [fusion_1114]  
    Fusion : COSMICHAS2 [8q24.13]  -  PLAG1 [8q12.1]  [fusion_1094]  [fusion_1095]  [fusion_1096]  [fusion_1100]  
    Fusion : COSMICLIFR [5p13.1]  -  PLAG1 [8q12.1]  [fusion_1091]  [fusion_1092]  [fusion_1093]  [fusion_1101]  
    Fusion : COSMICPLAG1 [8q12.1]  -  CTNNB1 [3p22.1]  [fusion_1081]  [fusion_1082]  [fusion_1083]  [fusion_1084]  
    Fusion : COSMICTCEA1 [8q11.23]  -  PLAG1 [8q12.1]  [fusion_1085]  [fusion_1086]  [fusion_1090]  
    Fusion : TICdbCHCHD7 [8q12.1]  -  PLAG1 [8q12.1]
    Fusion : TICdbCOL1A2 [7q21.3]  -  PLAG1 [8q12.1]
    Fusion : TICdbLIFR [5p13.1]  -  PLAG1 [8q12.1]
    Fusion : TICdbTCEA1 [8q11.23]  -  PLAG1 [8q12.1]
    Fusion Cancer (Beijing)PLAG1 [8q12.1]  -  RPS4Y1 [Yp11.31]  [FUSC002071]
    Polymorphisms : SNP and Copy number variants
    NCBI Variation ViewerPLAG1 [hg38]
    dbSNP Single Nucleotide Polymorphism (NCBI)PLAG1
    dbVarPLAG1
    ClinVarPLAG1
    1000_GenomesPLAG1 
    Exome Variant ServerPLAG1
    ExAC (Exome Aggregation Consortium)PLAG1 (select the gene name)
    Genetic variants : HAPMAP5324
    Genomic Variants (DGV)PLAG1 [DGVbeta]
    DECIPHERPLAG1 [patients]   [syndromes]   [variants]   [genes]  
    CONAN: Copy Number AnalysisPLAG1 
    Mutations
    ICGC Data PortalPLAG1 
    TCGA Data PortalPLAG1 
    Broad Tumor PortalPLAG1
    OASIS PortalPLAG1 [ Somatic mutations - Copy number]
    Cancer Gene: CensusPLAG1 
    Somatic Mutations in Cancer : COSMICPLAG1  [overview]  [genome browser]  [tissue]  [distribution]  
    Mutations and Diseases : HGMDPLAG1
    LOVD (Leiden Open Variation Database)Whole genome datasets
    LOVD (Leiden Open Variation Database)LOVD 3.0 shared installation
    BioMutasearch PLAG1
    DgiDB (Drug Gene Interaction Database)PLAG1
    DoCM (Curated mutations)PLAG1 (select the gene name)
    CIViC (Clinical Interpretations of Variants in Cancer)PLAG1 (select a term)
    intoGenPLAG1
    NCG5 (London)PLAG1
    Cancer3DPLAG1(select the gene name)
    Impact of mutations[PolyPhen2] [SIFT Human Coding SNP] [Buck Institute : MutDB] [Mutation Assessor] [Mutanalyser]
    Diseases
    OMIM181030    603026   
    Orphanet23663   
    MedgenPLAG1
    Genetic Testing Registry PLAG1
    NextProtQ6DJT9 [Medical]
    TSGene5324
    GENETestsPLAG1
    Target ValidationPLAG1
    Huge Navigator PLAG1 [HugePedia]
    snp3D : Map Gene to Disease5324
    BioCentury BCIQPLAG1
    ClinGenPLAG1
    Clinical trials, drugs, therapy
    Chemical/Protein Interactions : CTD5324
    Chemical/Pharm GKB GenePA33378
    Clinical trialPLAG1
    Miscellaneous
    canSAR (ICR)PLAG1 (select the gene name)
    Probes
    Litterature
    PubMed66 Pubmed reference(s) in Entrez
    GeneRIFsGene References Into Functions (Entrez)
    CoreMinePLAG1
    EVEXPLAG1
    GoPubMedPLAG1
    iHOPPLAG1
    REVIEW articlesautomatic search in PubMed
    Last year publicationsautomatic search in PubMed

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