Frequent PLAG1 gene rearrangements in skin and soft tissue myoepithelioma with ductal differentiation Journal Article
| Authors: | Antonescu, C. R.; Zhang, L.; Sung, Y. S.; Mosquera, J. M.; Weinreb, I.; Katabi, N.; Fletcher, C. D. M. |
| Article Title: | Frequent PLAG1 gene rearrangements in skin and soft tissue myoepithelioma with ductal differentiation |
| Abstract: | A subset of cutaneous and superficial soft tissue myoepithelial (ME) tumors displays a distinct ductal component and closely resembles mixed tumors/pleomorphic adenomas of salivary gland. As PLAG1 and HMGA2 rearrangements are the most common genetic events in pleomorphic adenomas, we sought to investigate if these abnormalities are also present in the skin/soft tissue ME lesions. In contrast, half of the deep-seated soft tissue ME tumors lacking ductal differentiation are known to be genetically unrelated, showing EWSR1 rearrangements. FISH analysis to detect PLAG1 and HMGA2 abnormalities was performed in 35 ME tumors, nine skin and 26 soft tissue, lacking EWSR1 and FUS rearrangements. For the PLAG1-rearranged tumors, FISH and RACE were performed to identify potential fusion partners, including CTNNB1 (beta-catenin) on 3p21 and LIFR (leukemia inhibitory factor receptor) on 5p13. Recurrent PLAG1 rearrangement by FISH was detected in 13 (37%) lesions, including three (33%) in the skin and 10 (38%) in the soft tissue. All were classified as benign and all except one showed abundant tubulo-ductal differentiation (comprising 12/24 [50%] of all tumors with ductal structures). A LIFR-PLAG1 fusion was detected by RACE and then confirmed by FISH in one soft tissue ME tumor with tubular formation. No CTNNB1 or LIFR abnormalities were detected in any of the remaining PLAG1-rearranged tumors. No structural HMGA2 abnormalities were detected in any of the 22 ME lesions tested. A subset of cutaneous and soft tissue ME tumors appears genetically linked to their salivary gland counterparts, displaying frequent PLAG1 gene rearrangements and occasionally LIFR-PLAG1 fusion. © 2013 Wiley Periodicals, Inc. |
| Keywords: | adolescent; adult; clinical article; human tissue; aged; middle aged; unclassified drug; oncoprotein; dna-binding proteins; phenotype; in situ hybridization, fluorescence; reverse transcription polymerase chain reaction; gene amplification; gene expression; skin neoplasms; skin tumor; fluorescence in situ hybridization; gene rearrangement; oncogene proteins, fusion; salivary glands; beta catenin; chromosome 3p; soft tissue neoplasms; soft tissue tumor; chromosome 5p; carcinoma, ductal; copy number variation; myoepithelioma; leukemia inhibitory factor receptor; leukemia inhibitory factor receptor alpha subunit; high mobility group a2 protein; pleomorphic adenoma gene 1 protein; hmga2 protein |
| Journal Title: | Genes Chromosomes and Cancer |
| Volume: | 52 |
| Issue: | 7 |
| ISSN: | 1045-2257 |
| Publisher: | Wiley Periodicals, Inc |
| Date Published: | 2013-07-01 |
| Start Page: | 675 |
| End Page: | 682 |
| Language: | English |
| DOI: | 10.1002/gcc.22063 |
| PROVIDER: | scopus |
| PUBMED: | 23630011 |
| PMCID: | PMC4041540 |
| DOI/URL: | |
| Notes: | --- - "Export Date: 3 June 2013" - "CODEN: GCCAE" - "Source: Scopus" |
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