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• W1992290890 abstract "Over 90% of Ewing sarcoma/primitive neuroectodermal tumors (PNETs) feature an 11;22 translocation leading to an EWSR1–FLI1 fusion. Less commonly, a member of the ETS-transcription factor family other than FLI1 is fused with EWSR1. In this study, cytogenetic analysis of an extraskeletal Ewing sarcoma/PNET revealed a novel chromosomal translocation t(4;22)(q31;q12) as the sole anomaly. Following confirmation of an EWSR1 rearrangement by the use of EWSR1 breakpoint flanking probes, a fluorescence in situ hybridization positional cloning strategy was used to further narrow the 4q31 breakpoint. These analyses identified the breakpoint within RP11-481K16, a bacterial artificial chromosome (BAC) clone containing two gene candidates FREM and SMARCA5. Subsequent RACE, RT–PCR, and sequencing studies were conducted to further characterize the fusion transcript. An in-frame fusion of the first 7 exons of EWSR1 to the last 19 exons of SMARCA5 was identified. SMARCA5 encodes for hSNF2H, a chromatin-remodeling protein. Analogous to EWSR1–ETS-expressing NIH3T3 cells, NIH3T3 cells expressing EWSR1–hSNF2H exhibited anchorage-independent growth and formed colonies in soft agar, indicating chimeric protein tumorigenic potential. Conversely, expression of EWSR1–hSNF2H in NIH3T3 cells, unlike EWSR1–ETS fusions, did not induce EAT-2 expression. Mapping analysis demonstrated that deletion of the C-terminus (SLIDE or SANT motives) of hSNF2H impaired, and deletion of the SNF2_N domain fully abrogated NIH3T3 cell transformation by EWSR1–SMARCA5. It is proposed that EWSR1–hSNF2H may act as an oncogenic chromatin-remodeling factor and that its expression contributes to Ewing sarcoma/primitive neuroectodermal tumorigenesis. To the best of our knowledge, this is the first description of a fusion between EWSR1 and a chromatin-reorganizing gene in Ewing sarcoma/PNET and thus expands the EWSR1 functional partnership beyond transcription factor and zinc-finger gene families." @default.
• W1992290890 created "2016-06-24" @default.
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• W1992290890 date "2011-03-01" @default.
• W1992290890 modified "2023-10-12" @default.
• W1992290890 title "A novel t(4;22)(q31;q12) produces an EWSR1–SMARCA5 fusion in extraskeletal Ewing sarcoma/primitive neuroectodermal tumor" @default.
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• W1992290890 doi "https://doi.org/10.1038/modpathol.2010.201" @default.
• W1992290890 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/21113140" @default.
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