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Ewing sarcoma with FEV gene rearrangements is a rare subset with predilection for extraskeletal locations and aggressive behavior
Author(s) -
Tsuda Yusuke,
Dickson Brendan C.,
Swanson David,
Sung YunShao,
Zhang Lei,
Meyers Paul,
Healey John H.,
Antonescu Cristina R.
Publication year - 2020
Publication title -
genes, chromosomes and cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.754
H-Index - 119
eISSN - 1098-2264
pISSN - 1045-2257
DOI - 10.1002/gcc.22828
Subject(s) - fli1 , fusion gene , fluorescence in situ hybridization , sarcoma , breakpoint , immunophenotyping , exon , biology , gene , pathology , gene rearrangement , chromosomal translocation , cancer research , microbiology and biotechnology , medicine , genetics , chromosome , flow cytometry
Abstract The molecular hallmark of Ewing sarcoma (ES) is a fusion involving the EWSR1 gene and a member of the ETS family of transcription factors. EWSR1‐FLI1 is the most common variant, occurring in 90% of cases, followed by EWSR1‐ERG . In a small subset, the FUS gene can substitute for EWSR1 in these fusions. Only rare case reports have been described to date of ES with FEV gene rearrangements. In this study, we investigate the clinicopathologic and molecular features of 10 ES patients with FEV ‐rearrangements, either fused to EWSR1 (n = 4) or to FUS (n = 6). The median age at diagnosis was 38 years (range, 5‐61 years); occurring in six males and four females. All tumors were located at extraskeletal sites, occurring more often in the axial soft tissues. Tumors had a similar morphologic appearance and immunophenotype as ES with more common EWSR1‐ETS fusions. Of six patients with follow‐up data, five patients (83%) developed metastasis and two patients (33%) died of their diseases. The diagnosis was confirmed either by fluorescence in situ hybridization and/or targeted RNA sequencing. In the five cases tested by targeted sequencing, the fusion transcripts were composed of EWSR1 or FUS fused to either exon 1 or 2 of FEV , retaining the FEV ETS DNA binding domain. This is the largest study to date investigating the ES subset with EWSR1/FUS‐FEV fusions showing a predilection for extraskeletal sites and aggressive behavior.