Published online before print July 9, 2007

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Copyright © 2007 American Society for Investigative Pathology
Journal of Molecular Diagnostics, doi:10.2353/jmoldx.2007.070009

Accepted for publication March 16, 2007.

Article

Ewing Sarcoma with Novel Translocation t(2;16) Producing an In-Frame Fusion of FUS and FEV

Tony L. Ng^*, Maureen J. O'Sullivan^*, Catherine J. Pallen, Malcolm Hayes, Paul W. Clarkson, Mark Winstanley^¶, Poul H.B. Sorensen^*||, Torsten O. Nielsen^*, and Douglas E. Horsman^@

From the Department of Pathology and Laboratory Medicine,* University of British Columbia, Vancouver, British Columbia; the Department of Pediatrics, Child and Family Research Institute, University of British Columbia, Vancouver; the Department of Pathology and Laboratory Medicine, British Columbia Cancer Agency, University of British Columbia, Vancouver; the Division of Surgical Oncology, British Columbia Cancer Agency, Vancouver; the Department of Oncology, Hematology and BMT,^¶ British Columbia Children's Hospital, Vancouver; and the Department of Molecular Oncology,^|| British Columbia Cancer Research Centre, University of British Columbia, Vancouver, British Columbia, Canada

^@ To whom correspondence should be addressed. E-mail: dhorsman{at}bccancer.bc.ca.

	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.

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