PLAG1 (Pleomorphic adenoma gene 1)

2002-06-01   David Gisselsson 

Department of Clinical Genetics, University Hospital, SE-221 85 Lund, Sweden

Identity

HGNC
PLAG1
LOCATION
8q12.1
LOCUSID
5324
ALIAS
PSA,SGPA,SRS4,ZNF912
FUSION GENES
Show Gene Fusions

DNA/RNA

Atlas Image
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

Proteins

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

Entity name
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 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.
    • Fusion protein
    Fusions occur in the 5 regulatory regions, leading to promoter swapping and activation of PLAG1 expression while preserving coding sequences.
    Entity name
    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 gene
    Intragenic PLAG1 rearrangements demonstrated by fluorescence in situ hybridisation.
    Entity name
    Lipoblastoma
    Disease
    Benign fat-forming tumour of childhood
    Prognosis
    Recovery after surgical removal
    Cytogenetics
    Structural abnormalities involving 8q11-13
    Hybrid 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
    • Fusion protein
    Fusions occur in the 5 regulatory regions, leading promoter swapping and activation of PLAG1 expression while preserving coding sequences.

    Breakpoints

    Atlas Image

    Bibliography

    Pubmed IDLast YearTitleAuthors
    100290851999Conserved 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 et al
    108119812000Evidence of involvement of the PLAG1 gene in lipoblastomas.Astrom A et al
    118826542002Identification of a karyopherin alpha 2 recognition site in PLAG1, which functions as a nuclear localization signal.Braem CV et al
    115556762001Histologic 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 et al
    118941142002Expression of PLAG1 and HMGIC proteins and fusion transcripts in radiation-associated pleomorphic adenomas.Enlund F et al
    115495882001PLAG1 alterations in lipoblastoma: involvement in varied mesenchymal cell types and evidence for alternative oncogenic mechanisms.Gisselsson D et al
    118889282002The tumorigenic diversity of the three PLAG family members is associated with different DNA binding capacities.Hensen K et al
    109873002000PLAG1 fusion oncogenes in lipoblastoma.Hibbard MK et al
    111354322001Characterization of chromosome aberrations in salivary gland tumors by FISH, including multicolor COBRA-FISH.Jin C et al
    92686381997A 2-Mb YAC contig and physical map covering the chromosome 8q12 breakpoint cluster region in pleomorphic adenomas of the salivary glands.Kas K et al
    97225271998Transcriptional activation capacity of the novel PLAG family of zinc finger proteins.Kas K et al
    103345691999Pleomorphic adenoma gene 1 is expressed in cultured benign and malignant salivary gland tumor cells.Queimado L et al
    98921121999Fluorescence in situ hybridization mapping of breakpoints in pleomorphic adenomas with 8q12-13 abnormalities identifies a subgroup of tumors without PLAG1 involvement.Röijer E et al
    117019662001Assignment of the rat pleiomorphic adenoma genes (Plag1, Plagl1, Plagl2) by in situ hybridization and radiation hybrid mapping.Szpirer C et al
    106468612000PLAG1, the main translocation target in pleomorphic adenoma of the salivary glands, is a positive regulator of IGF-II.Voz ML et al
    95257401998The 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 et al
    118429292000First insights into the molecular basis of pleomorphic adenomas of the salivary glands.Voz ML et al

    Other Information

    Locus ID:

    NCBI: 5324
    MIM: 603026
    HGNC: 9045
    Ensembl: ENSG00000181690

    Variants:

    dbSNP: 5324
    ClinVar: 5324
    TCGA: ENSG00000181690
    COSMIC: PLAG1

    RNA/Proteins

    Gene IDTranscript IDUniprot
    ENSG00000181690ENST00000316981Q6DJT9
    ENSG00000181690ENST00000316981A0A024R7Z0
    ENSG00000181690ENST00000423799Q6DJT9
    ENSG00000181690ENST00000429357Q6DJT9
    ENSG00000181690ENST00000429357A0A024R7Z0

    Expression (GTEx)

    0
    5
    10
    15
    Adipose - Subcutaneous
    Adipose - Visceral
    Adrenal Gland
    Artery - Aorta
    Artery - Tibial
    Bladder
    Brain - Amygdala
    Brain - Anterior cingulate cortex
    Brain - Caudate
    Brain - Cerebellar Hemisphere
    Brain - Cerebellum
    Brain - Cortex
    Brain - Frontal Cortex
    Brain - Hippocampus
    Brain - Hypothalamus
    Brain - Nucleus accumbens
    Brain - Putamen
    Brain - Spinal cord
    Brain - Substantia nigra
    Breast - Mammary Tissue
    Cells - Cultured fibroblasts
    Cells - EBV - transformed lymphocytes
    Cervix - Ectocervix
    Cervix - Endocervix
    Colon - Sigmoid
    Colon - Transverse
    Esophagus - Gastroesophageal Junction
    Esophagus - Mucosa
    Esophagus - Muscularis
    Fallopian Tube
    Heart - Atrial Appendage
    Heart - Left Ventricle
    Kidney - Cortex
    Kidney - Medulla
    Liver
    Lung
    Minor Salivary Gland
    Muscle - Skeletal
    Nerve - Tibial
    Ovary
    Pancreas
    Pituitary
    Prostate
    Skin - Not Sun Exposed
    Skin - Sun Exposed
    Small Intestine - Terminal Ileum
    Spleen
    Stomach
    Testis
    Thyroid
    Uterus
    Vagina
    Whole Blood

    References

    Pubmed IDYearTitleCitations
    196927022009miRNA deregulation by epigenetic silencing disrupts suppression of the oncogene PLAG1 in chronic lymphocytic leukemia.51
    192660772009Genetic determinants of height growth assessed longitudinally from infancy to adulthood in the northern Finland birth cohort 1966.48
    201899362010A genome-wide association study in 19 633 Japanese subjects identified LHX3-QSOX2 and IGF1 as adult height loci.47
    173329142007PLAG1, the prototype of the PLAG gene family: versatility in tumour development (review).41
    155856522005Plag1 and Plagl2 are oncogenes that induce acute myeloid leukemia in cooperation with Cbfb-MYH11.39
    159205572005PLAG1 gene alterations in salivary gland pleomorphic adenoma and carcinoma ex-pleomorphic adenoma: a combined study using chromosome banding, in situ hybridization and immunocytochemistry.30
    193479352009Alterations in miRNA processing and expression in pleomorphic adenomas of the salivary gland.29
    146959922004Amplification and overexpression of the IGF2 regulator PLAG1 in hepatoblastoma.28
    236300112013Frequent PLAG1 gene rearrangements in skin and soft tissue myoepithelioma with ductal differentiation.26
    220389202012A subset of cutaneous and soft tissue mixed tumors are genetically linked to their salivary gland counterpart.21

    Citation

    David Gisselsson

    PLAG1 (Pleomorphic adenoma gene 1)

    Atlas Genet Cytogenet Oncol Haematol. 2002-06-01

    Online version: http://atlasgeneticsoncology.org/gene/74/plag1-(pleomorphic-adenoma-gene-1)