Narasimhan P Agaram, Hsiao-Wei Chen, Lei Zhang, Yun-Shao Sung, David Panicek, John H Healey, G Petur Nielsen, Christopher D M Fletcher, Cristina R Antonescu
Genes, chromosomes & cancer 2015 FebThe genetics of myoepithelial tumors (ME) of soft tissue and bone have recently been investigated, with EWSR1-related gene fusions being seen in approximately half of the tumors. The fusion partners of EWSR1 so far described include POU5F1, PBX1, ZNF444 and, in a rare case, ATF1. We investigated by RNA sequencing an index case of EWSR1-rearranged ME of the tibia, lacking a known fusion partner, and identified a novel EWSR1-PBX3 fusion. The fusion was further validated by reverse transcriptase polymerase chain reaction and fluorescence in situ hybridization (FISH). To evaluate if this is a recurrent event, an additional cohort of 22 EWSR1-rearranged ME cases lacking a fusion partner were screened by FISH for abnormalities in PBX3 gene. Thus, two additional cases were identified showing an EWSR1-PBX3 gene fusion. One of them was also intraosseous involving the ankle, while the other occurred in the soft tissue of the index finger. The morphology of the EWSR1-PBX3 fusion positive cases showed similar findings, with nests or sheets of epithelioid to spindle cells in a partially myxoid to collagenous matrix. All three cases showed expression of S100 and EMA by immunohistochemistry. In summary, we report a novel EWSR1-PBX3 gene fusion in a small subset of ME, thereby expanding the spectrum of EWSR1-related gene fusions seen in these tumors. This gene fusion seems to occur preferentially in skeletal ME, with two of the three study cases occurring in intraosseous locations. © 2014 Wiley Periodicals, Inc.
Narasimhan P Agaram, Hsiao-Wei Chen, Lei Zhang, Yun-Shao Sung, David Panicek, John H Healey, G Petur Nielsen, Christopher D M Fletcher, Cristina R Antonescu. EWSR1-PBX3: a novel gene fusion in myoepithelial tumors. Genes, chromosomes & cancer. 2015 Feb;54(2):63-71
PMID: 25231231
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