title: Ewing sarcoma with novel translocation t(2;16) producing an in-frame fusion of FUS and FEV.
abstract: Ewing family tumors are molecularly characterized by expression of chimeric transcripts generated by specific chromosomal translocations, most commonly involving fusion of the EWS gene to a member of the ETS family of transcription factors (including FLI1, ERG, ETV1, E1AF, and FEV). Approximately 85% of reported cases of Ewing sarcoma bear an EWS-FLI1 fusion. In rare cases, FUS can substitute for EWS, with translocation t(16;21)(p11;q24) producing a FUS-ERG fusion with no EWS rearrangement. We report a case of Ewing sarcoma, presenting as a pathological fracture of the distal clavicle in a 33-year-old male, in which cytogenetic analysis revealed a single t(2;16)(q35;p11) balanced translocation. Fluorescence in situ hybridization using a commercially available diagnostic probe was negative for an EWS gene rearrangement; instead, break-apart fluorescence in situ hybridization probes for FUS and FEV were positive for a translocation involving these genes. Cloning and sequencing of the breakpoint region demonstrated an in-frame fusion of FUS to FEV. In conclusion, this represents the first reported case of Ewing family tumors demonstrating a variant translocation involving FUS and FEV and highlights the need to consider alternative permutations of fusion partners for molecular diagnosis of sarcomas.
authors.affiliation: Department of Pathology and Laboratory Medicine, British Columbia Cancer Agency, 600 W. 10th Ave., Vancouver, BC, Canada, V5Z 4E6.
authors.forename: Tony L
authors.initials: TL
authors.lastname: Ng
authors.forename: Maureen J
authors.initials: MJ
authors.lastname: O'Sullivan
authors.forename: Catherine J
authors.initials: CJ
authors.lastname: Pallen
authors.forename: Malcolm
authors.initials: M
authors.lastname: Hayes
authors.forename: Paul W
authors.initials: PW
authors.lastname: Clarkson
authors.forename: Mark
authors.initials: M
authors.lastname: Winstanley
authors.forename: Poul H B
authors.initials: PH
authors.lastname: Sorensen
authors.forename: Torsten O
authors.initials: TO
authors.lastname: Nielsen
authors.forename: Douglas E
authors.initials: DE
authors.lastname: Horsman
mesh_terms: D000328:Adult; D001483:Base Sequence; D002885:Chromosomes, Human, Pair 16 / Q000235:genetics*; D002889:Chromosomes, Human, Pair 2 / Q000235:genetics*; D006801:Humans; D007150:Immunohistochemistry; D017404:In Situ Hybridization, Fluorescence; D008297:Male; D008677:Metaphase; D008969:Molecular Sequence Data; D020411:Oligonucleotide Array Sequence Analysis; D015514:Oncogene Proteins, Fusion / Q000737:chemistry / Q000235:genetics*; D012512:Sarcoma, Ewing / Q000235:genetics* / Q000473:pathology; D017422:Sequence Analysis, DNA; D014178:Translocation, Genetic / Q000235:genetics*
chemical_list: C419546:EWS-FEV fusion protein, human; C524590:EWS-FUS protein, human; D015514:Oncogene Proteins, Fusion