Ewing sarcoma with ERG gene rearrangements: A molecular study focusing on the prevalence of FUS-ERG and common pitfalls in detecting EWSR1-ERG fusions by FISH Journal Article
| Authors: | Chen, S.; Deniz, K.; Sung, Y. S.; Zhang, L.; Dry, S.; Antonescu, C. R. |
| Article Title: | Ewing sarcoma with ERG gene rearrangements: A molecular study focusing on the prevalence of FUS-ERG and common pitfalls in detecting EWSR1-ERG fusions by FISH |
| Abstract: | The genetics of Ewing sarcoma (ES) are characterized by a canonical fusion involving EWSR1 gene and a member of the ETS family of transcription factors, such as FLI1 and ERG. In fact, ERG gene rearrangements represent the second most common molecular alteration, with EWSR1-ERG being identified in 5-10% of cases, while only a handful of reports document a FUS-ERG fusion. In this study, we focus on ES with ERG gene abnormalities, specifically to investigate the prevalence and clinicopathologic features of FUS-ERG fusions in a large cohort of small blue round cell tumors (SBRCTs) and compare to the eight reported FUS-positive ES. Among the 85 SBRCTs tested, seven (8.2%) cases harbored FUS gene rearrangements; six fused to ERG and one with FEV. During this investigation we came across a number of ERG-rearranged ES lacking both EWSR1 and FUS abnormalities by FISH. In one case, RNA sequencing identified an EWSR1-ERG transcript despite the negative EWSR1 rearrangements by FISH. Additional 3-color FISH fusion assay demonstrated the fusion of EWSR1 and ERG signals in all four cases negative for break-apart EWSR1 FISH. These results emphasize a potential pitfall of relying on EWSR1 FISH assay alone for diagnosis of ES. In cases with classic morphology and/or strong CD99 and ERG immunoreactivity, additional molecular testing should be applied, such as ERG FISH or RT-PCR/next generation sequencing, for a more definitive diagnosis. Although our study group is small, there were no differences noted between the clinical, morphologic features and immunoprofile of the different subsets of ERG-rearranged SBRCTs. © 2015 Wiley Periodicals, Inc. |
| Journal Title: | Genes Chromosomes and Cancer |
| Volume: | 55 |
| Issue: | 4 |
| ISSN: | 1045-2257 |
| Publisher: | Wiley Periodicals, Inc |
| Date Published: | 2016-04-01 |
| Start Page: | 340 |
| End Page: | 349 |
| Language: | English |
| DOI: | 10.1002/gcc.22336 |
| PROVIDER: | scopus |
| PUBMED: | 26690869 |
| PMCID: | PMC5006947 |
| DOI/URL: | |
| Notes: | Article -- Export Date: 3 March 2016 -- Source: Scopus |
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