| Written | 2002-06 | David Gisselsson |
| Department of Clinical Genetics, University Hospital, SE-221 85 Lund, Sweden |
| Identity |
| Alias_names | pleiomorphic 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 2017) | Data from Atlas, Mitelman, Cosmic Fusion, Fusion Cancer, TCGA fusion databases with official HUGO symbols (see references in chromosomal bands) |
| 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) / HACD4 (9p21.3) | PLAG1 (8q12.1) / HAS2 (8q24.13) | PLAG1 (8q12.1) / LIFR (5p13.1) | |
| PLAG1 (8q12.1) / RPS4Y1 (Yp11.2) | PLAG1 (8q12.1) / RPS4Y1 (Yp11.31) | PLAG1 (8q12.1) / TCEA1 (8q11.23) | |
| PLAG1 (8q12.1) / TRBJ2-7 (7q34) | RAB2A (8q12.1) / PLAG1 (8q12.1) | RAD51B (14q24.1) / PLAG1 (8q12.1) | |
| TCEA1 (8q11.23) / 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: |
| 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: |
| 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 Leukemias implicated (Data extracted from papers in the Atlas) [ 1 ] |
|
t(7;8)(q34;q12) PLAG1/TRBJ2-7
|
| Other Solid tumors implicated (Data extracted from papers in the Atlas) [ 11 ] |
| External links |
| REVIEW articles | automatic search in PubMed |
| Last year publications | automatic search in PubMed |
| © Atlas of Genetics and Cytogenetics in Oncology and Haematology | indexed on : Mon Sep 3 16:02:11 CEST 2018 |
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