Download Gene Section PLAG1 (Pleomorphic adenoma gene 1) Atlas of Genetics and Cytogenetics

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Gene Section
Mini Review
PLAG1 (Pleomorphic adenoma gene 1)
David Gisselsson
Department of Clinical Genetics, Lund University Hospital, 221 85 Lund, Sweden (DG)
Published in Atlas Database: June 2002
Online updated version: http://AtlasGeneticsOncology.org/Genes/PLAG1ID74.html
DOI: 10.4267/2042/37897
This work is licensed under a Creative Commons Attribution-Noncommercial-No Derivative Works 2.0 France Licence.
© 2002 Atlas of Genetics and Cytogenetics in Oncology and Haematology
Localisation
Identity
Nuclear.
HGNC (Hugo): PLAG1
Location: 8q12
Local order: (316 cR / 86 Mb from 8pter)
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.
DNA/RNA
Description
7313 bp, 5 exons, 4 introns.
Transcription
Homology
At least two splicing variants, including and excluding
the second exon.
Mouse and rat Plag1.
Mutations
Protein
Somatic
Description
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.
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.
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.
Atlas Genet Cytogenet Oncol Haematol. 2002; 6(4)
283
PLAG1 (Pleomorphic adenoma gene 1)
Gisselsson D
Implicated in
References
Pleomorphic adenoma of the salivary
gland
Kas K, Röijer E, Voz M, Meyen E, Stenman G, Van de Ven
WJ. A 2-Mb YAC contig and physical map covering the
chromosome 8q12 breakpoint cluster region in pleomorphic
adenomas of the salivary glands. Genomics. 1997 Aug
1;43(3):349-58
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.
Kas K, Voz ML, Röijer E, Aström AK, Meyen E, Stenman G,
Van de Ven WJ. Promoter swapping between the genes for a
novel zinc finger protein and beta-catenin in pleiomorphic
adenomas with t(3;8)(p21;q12) translocations. Nat Genet. 1997
Feb;15(2):170-4
Kas K, Voz ML, Hensen K, Meyen E, Van de Ven WJ.
Transcriptional activation capacity of the novel PLAG family of
zinc finger proteins. J Biol Chem. 1998 Sep 4;273(36):2302632
Voz ML, Aström AK, Kas K, Mark J, Stenman G, Van de Ven
WJ. The recurrent translocation t(5;8)(p13;q12) in pleomorphic
adenomas results in upregulation of PLAG1 gene expression
under control of the LIFR promoter. Oncogene. 1998
Mar;16(11):1409-16
Aström AK, Voz ML, Kas K, Röijer E, Wedell B, Mandahl N,
Van de Ven W, Mark J, Stenman G. Conserved mechanism of
PLAG1 activation in salivary gland tumors with and without
chromosome 8q12 abnormalities: identification of SII as a new
fusion partner gene. Cancer Res. 1999 Feb 15;59(4):918-23
Queimado L, Lopes C, Du F, Martins C, Bowcock AM, Soares
J, Lovett M. Pleomorphic adenoma gene 1 is expressed in
cultured benign and malignant salivary gland tumor cells. Lab
Invest. 1999 May;79(5):583-9
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.
Röijer E, Kas K, Behrendt M, Van de Ven W, Stenman G.
Fluorescence in situ hybridization mapping of breakpoints in
pleomorphic adenomas with 8q12-13 abnormalities identifies a
subgroup of tumors without PLAG1 involvement. Genes
Chromosomes Cancer. 1999 Jan;24(1):78-82
Astrom A, D'Amore ES, Sainati L, Panarello C, Morerio C,
Mark J, Stenman G. Evidence of involvement of the PLAG1
gene in lipoblastomas. Int J Oncol. 2000 Jun;16(6):1107-10
Hibbard MK, Kozakewich HP, Dal Cin P, Sciot R, Tan X, Xiao
S, Fletcher JA. PLAG1 fusion oncogenes in lipoblastoma.
Cancer Res. 2000 Sep 1;60(17):4869-72
Lipoblastoma
Voz ML, Agten NS, Van de Ven WJ, Kas K. PLAG1, the main
translocation target in pleomorphic adenoma of the salivary
glands, is a positive regulator of IGF-II. Cancer Res. 2000 Jan
1;60(1):106-13
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.
Atlas Genet Cytogenet Oncol Haematol. 2002; 6(4)
Voz ML, Van de Ven WJ, Kas K. First insights into the
molecular basis of pleomorphic adenomas of the salivary
glands. Adv Dent Res. 2000 Dec;14:81-3
Debiec-Rychter M, Van Valckenborgh I, Van den Broeck C,
Hagemeijer A, Van de Ven WJ, Kas K, Van Damme B, Voz
ML. Histologic localization of PLAG1 (pleomorphic adenoma
gene 1) in pleomorphic adenoma of the salivary gland:
cytogenetic evidence of common origin of phenotypically
diverse cells. Lab Invest. 2001 Sep;81(9):1289-97
Gisselsson D, Hibbard MK, Dal Cin P, Sciot R, Hsi BL,
Kozakewich HP, Fletcher JA. PLAG1 alterations in
lipoblastoma: involvement in varied mesenchymal cell types
and evidence for alternative oncogenic mechanisms. Am J
Pathol. 2001 Sep;159(3):955-62
284
PLAG1 (Pleomorphic adenoma gene 1)
Gisselsson D
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. Characterization of chromosome
aberrations in salivary gland tumors by FISH, including
multicolor COBRA-FISH. Genes Chromosomes Cancer. 2001
Feb;30(2):161-7
Enlund F, Nordkvist A, Sahlin P, Mark J, Stenman G.
Expression of PLAG1 and HMGIC proteins and fusion
transcripts in radiation-associated pleomorphic adenomas. Int
J Oncol. 2002 Apr;20(4):713-6
Hensen K, Van Valckenborgh IC, Kas K, Van de Ven WJ, Voz
ML. The tumorigenic diversity of the three PLAG family
members is associated with different DNA binding capacities.
Cancer Res. 2002 Mar 1;62(5):1510-7
Szpirer C, Kas K, Laes JF, Rivière M, Van Vooren P, Szpirer J.
Assignment of the rat pleiomorphic adenoma genes (Plag1,
Plagl1, Plagl2) by in situ hybridization and radiation hybrid
mapping. Cytogenet Cell Genet. 2001;94(1-2):94-5
This article should be referenced as such:
Braem CV, Kas K, Meyen E, Debiec-Rychter M, Van De Ven
WJ, Voz ML. Identification of a karyopherin alpha 2 recognition
site in PLAG1, which functions as a nuclear localization signal.
J Biol Chem. 2002 May 31;277(22):19673-8
Atlas Genet Cytogenet Oncol Haematol. 2002; 6(4)
Gisselsson D. PLAG1 (Pleomorphic adenoma gene 1). Atlas
Genet Cytogenet Oncol Haematol. 2002; 6(4):283-285.
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