Ewing sarcoma with FEV gene rearrangements is a rare subset with predilection for extraskeletal locations and aggressive behavior Journal Article
| Authors: | Tsuda, Y.; Dickson, B. C.; Swanson, D.; Sung, Y. S.; Zhang, L.; Meyers, P.; Healey, J. H.; Antonescu, C. R. |
| Article Title: | Ewing sarcoma with FEV gene rearrangements is a rare subset with predilection for extraskeletal locations and aggressive behavior |
| 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. © 2019 Wiley Periodicals, Inc. |
| Keywords: | adolescent; adult; child; controlled study; human tissue; preschool child; middle aged; cancer surgery; young adult; human cell; major clinical study; exon; clinical feature; histopathology; doxorubicin; cancer combination chemotherapy; bone metastasis; postoperative care; preoperative care; follow up; gene; gene targeting; tumor localization; etoposide; cyclophosphamide; vincristine; genetic transcription; retrospective study; cancer mortality; ifosfamide; ewing sarcoma; soft tissue; lung metastasis; fluorescence in situ hybridization; gene rearrangement; gene fusion; immunophenotyping; dna binding; ets gene; transcription factor ets; gene fusions; ewsr1 gene; fus gene; ets; ewsr1; human; male; female; priority journal; article; fus; rna sequencing; fev; rna binding protein fus; fev gene |
| Journal Title: | Genes Chromosomes and Cancer |
| Volume: | 59 |
| Issue: | 5 |
| ISSN: | 1045-2257 |
| Publisher: | Wiley Periodicals, Inc |
| Date Published: | 2020-05-01 |
| Start Page: | 286 |
| End Page: | 294 |
| Language: | English |
| DOI: | 10.1002/gcc.22828 |
| PUBMED: | 31756779 |
| PROVIDER: | scopus |
| PMCID: | PMC7135932 |
| DOI/URL: | |
| Notes: | Article -- Source: Scopus |
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