Undifferentiated small round cell sarcomas with rare EWS gene fusions: Identification of a novel EWS-SP3 fusion and of additional cases with the EWS-ETV1 and EWS-FEV fusions Journal Article
| Authors: | Wang, L.; Bhargava, R.; Zheng, T.; Wexler, L.; Collins, M. H.; Roulston, D.; Ladanyi, M. |
| Article Title: | Undifferentiated small round cell sarcomas with rare EWS gene fusions: Identification of a novel EWS-SP3 fusion and of additional cases with the EWS-ETV1 and EWS-FEV fusions |
| Abstract: | Ewing family tumors (EFTs) are prototypical primitive small round blue cell sarcomas arising in bone or extraskeletal soft tissues in children or adolescents. EFTs show fusions of EWS with a gene of the ETS family of transcription factors, either EWS-FLI1 (90 to 95%) or EWS-ERG (5 to 10%). Rare cases with fusions of EWS to other ETS family genes, such as ETVI, E1AF, and FEV, have been identified, but their clinicopathological similarity to classic EFTs remains unclear. We report four new cases of EFT-like tumors with rare EWS fusions, including two with EWS-ETV1, one with EWS-FEV, and a fourth case in which we cloned a novel EWS-SP3 fusion, the first known cancer gene fusion involving a gene of the Sp zinc finger family. Analysis of these three new cases along with data on nine previously reported cases with fusions of EWS to ETV1, E1AF, or FEV suggest a strong predilection for extraskeletal primary sites. EFT-like cases with fusions of EWS to non-ETS translocation partners are also uncommon but involve the same aminoterminal portion of EWS, which in our novel EWS-SP3 fusion is joined to the SP3 zinc-finger DNA-binding domain. As these data further support, these types of EWS fusions are associated with primitive extraskeletal small round cell sarcomas of uncertain lineage arising mainly in the pediatric population. Copyright © American Society for Investigative Pathology and the Association for Molecular Pathology. |
| Keywords: | adolescent; adult; cancer chemotherapy; child; human tissue; preschool child; child, preschool; cancer surgery; unclassified drug; oncoprotein; gene sequence; gene translocation; exon; genetics; case report; cisplatin; doxorubicin; cancer radiotherapy; drug megadose; molecular genetics; carboplatin; reverse transcription polymerase chain reaction; gene amplification; etoposide; transcription factor; cyclophosphamide; vincristine; pathology; ifosfamide; transcription factors; irinotecan; rna; molecular cloning; chemistry; molecular sequence data; amino terminal sequence; reverse transcriptase polymerase chain reaction; nucleotide sequence; gene fusion; oncogene proteins, fusion; base sequence; dna mutational analysis; protein family; dna binding; rna binding protein ews; zinc finger protein; karyotyping; rna extraction; small cell sarcoma; pirarubicin; razoxane; sarcoma, small cell; e1a protein; ews etv1 fusion protein, human; ews fev fusion protein, human; ews sp3 fusion protein, human; ews-etv1 fusion protein, human; ews-fev fusion protein, human; ews-sp3 fusion protein, human |
| Journal Title: | Journal of Molecular Diagnostics |
| Volume: | 9 |
| Issue: | 4 |
| ISSN: | 1525-1578 |
| Publisher: | Elsevier Science, Inc. |
| Date Published: | 2007-09-01 |
| Start Page: | 498 |
| End Page: | 509 |
| Language: | English |
| DOI: | 10.2353/jmoldx.2007.070053 |
| PUBMED: | 17690209 |
| PROVIDER: | scopus |
| PMCID: | PMC1975108 |
| DOI/URL: | |
| Notes: | --- - "Cited By (since 1996): 29" - "Export Date: 17 November 2011" - "CODEN: JMDIF" - "Source: Scopus" |
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