title: EWSR1-PBX3: a novel gene fusion in myoepithelial tumors.
abstract: The 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.
authors.affiliation: Department of Pathology, Memorial Sloan Kettering Cancer Center, New York, NY.
authors.forename: Narasimhan P
authors.initials: NP
authors.lastname: Agaram
authors.forename: Hsiao-Wei
authors.initials: HW
authors.lastname: Chen
authors.forename: Lei
authors.initials: L
authors.lastname: Zhang
authors.forename: Yun-Shao
authors.initials: YS
authors.lastname: Sung
authors.forename: David
authors.initials: D
authors.lastname: Panicek
authors.forename: John H
authors.initials: JH
authors.lastname: Healey
authors.forename: G Petur
authors.initials: GP
authors.lastname: Nielsen
authors.forename: Christopher D M
authors.initials: CD
authors.lastname: Fletcher
authors.forename: Cristina R
authors.initials: CR
authors.lastname: Antonescu
mesh_terms: D000328:Adult; D001483:Base Sequence; D001859:Bone Neoplasms / Q000175:diagnosis / Q000235:genetics*; D002148:Calmodulin-Binding Proteins / Q000235:genetics*; D018398:Homeodomain Proteins / Q000235:genetics*; D006801:Humans; D008297:Male; D008969:Molecular Sequence Data; D009208:Myoepithelioma / Q000175:diagnosis / Q000235:genetics*; D050596:Oncogene Fusion; D011518:Proto-Oncogene Proteins / Q000235:genetics*; D034802:RNA-Binding Protein EWS; D016601:RNA-Binding Proteins / Q000235:genetics*
chemical_list: D002148:Calmodulin-Binding Proteins; C500986:EWSR1 protein, human; D018398:Homeodomain Proteins; D011518:Proto-Oncogene Proteins; D034802:RNA-Binding Protein EWS; D016601:RNA-Binding Proteins; C090466:proto-oncogene protein Pbx3