Abstract IA15: Genetic and phenotypic diversity in Ewing sarcoma

摘要: Ewing sarcoma is typically a bone tumor of adolescence characterized by small round cell phenotype, CD99 membrane staining and presence gene fusion between FET family members (most frequently EWSR1, much more rarely FUS/TLS or TAF15) the ETS transcription factors (mainly FLI1 ERG, others). A first diversity relates to type fusion. Indeed, recently, other types fusions have been observed in tumors suspected be but lacking typical These collectively named Ewing-like sarcoma. They include with CIC-DUX4, EWSR1-NFATc2, BCOR-CCNB3 EWSR1-PATZ1 fusions. To precisely investigate relationships these different we screened large bank soft tissue for then profiled expression set 117 FET-ETS, 12 BCOR-CCNB3, 8 EWSR1-NFATc 5 cases. Results strongly suggest that there strong homogeneity within each categories define biological entities. In addition, when clinical characteristics are investigated some important differences observed. mostly concern age onset primary localization tumor. second concerns secondary genetic alterations. collaboration Pediatric Cancer Genome Project at St Jude studied series 112 sarcomas whole genome sequencing comparing germline DNA. Overall, had relatively few single-nucleotide variants, indels, structural copy-number Apart from chromosome arm changes, most common somatic mutations were detected STAG2 (17%), CDKN2A (12%), TP53 (7%), EZH2, BCOR, ZMYM3 (2.7% each). Strikingly, deletions mutually exclusive, as confirmed lines. an expanded cohort 299 patients data, discovered often concurrent associated poor outcome. Finally, subclonal diagnostic expansion STAG2-immunonegative cells relapsed compared matched samples. Another level cell-to-cell phenotypic heterogeneity population same background. investigations including FACS, single RNA seq functional analyses non-genetic plays crucial role variety related processes migration, resistance ability seed distant organs. Citation Format: Olivier Delattre. Genetic [abstract]. In: Proceedings AACR Special Conference on Advances Research: From Mechanisms Models Treatment Survivorship; 2015 Nov 9-12; Fort Lauderdale, FL. Philadelphia (PA): AACR; Res 2016;76(5 Suppl):Abstract nr IA15.