title: EWSR1-CREB3L1 gene fusion: a novel alternative molecular aberration of low-grade fibromyxoid sarcoma.
abstract: Low-grade fibromyxoid sarcoma (LGFMS) is an uncommon sarcoma with a deceptively bland-looking morphology that disguises its malignant clinical behavior. It shows distinctive chromosomal translocations resulting in fusion of FUS with the CREB3L2 gene in most cases and CREB3L1 in rare cases. Thus molecular studies are particularly helpful in the diagnosis of this bland-looking sarcoma. We report 2 cases of LGFMS serendipitously found to harbor a novel alternative EWSR1-CREB3L1 gene fusion, as confirmed by DNA sequencing of reverse transcriptase-polymerase chain reaction products and fluorescence in situ hybridization. One patient was a child who presented with a subcutaneous nodule on the lower leg, and the other was a middle-aged woman who had a mass lesion over the proximal thigh. Morphologically, one case showed a spindle cell tumor with hyalinization and giant rosettes, whereas the other showed classical histology of LGFMS with focal metaplastic bone formation. Immunostaining for MUC4 showed extensive positive staining. Our findings therefore expand the spectrum of gene fusions that characterize LGFMS and suggest that the EWSR1 gene may substitute for the function of FUS in gene fusions of sarcoma.
authors.affiliation: Department of Pathology, Queen Elizabeth Hospital, Hong Kong, SAR China.
authors.forename: Patrick P L
authors.initials: PP
authors.lastname: Lau
authors.forename: Philip C W
authors.initials: PC
authors.lastname: Lui
authors.forename: Gene T C
authors.initials: GT
authors.lastname: Lau
authors.forename: Derek T W
authors.initials: DT
authors.lastname: Yau
authors.forename: Elaine T Y
authors.initials: ET
authors.lastname: Cheung
authors.forename: John K C
authors.initials: JK
authors.lastname: Chan
mesh_terms: D002148:Calmodulin-Binding Proteins / Q000235:genetics*; D002648:Child; D017362:Cyclic AMP Response Element-Binding Protein / Q000235:genetics*; D005260:Female; D005354:Fibrosarcoma / Q000235:genetics*; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D008297:Male; D008875:Middle Aged; D060787:Neoplasm Grading; D009419:Nerve Tissue Proteins / Q000235:genetics*; D015514:Oncogene Proteins, Fusion; D034802:RNA-Binding Protein EWS; D016601:RNA-Binding Proteins / Q000235:genetics*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012983:Soft Tissue Neoplasms / Q000235:genetics*
chemical_list: C485618:CREB3L1 protein, human; D002148:Calmodulin-Binding Proteins; D017362:Cyclic AMP Response Element-Binding Protein; C500986:EWSR1 protein, human; D009419:Nerve Tissue Proteins; D015514:Oncogene Proteins, Fusion; D034802:RNA-Binding Protein EWS; D016601:RNA-Binding Proteins