Abstract IA02: Identity shifts in pediatric cancers

摘要: In contrast to adult cancers, most pediatric malignancies display limited genetic heterogeneity. Ewing sarcoma, the major driver of tumor development is expression chimeric EWSR1-FLI1 transcription factor, which results from a chromosome translocation. Additional recurrent alterations include CDKN2A, STAG2, and TP53 genes. Through its binding specific elements including GGAA microsatellite sequences, has impact on epigenetic landscape cancer cells consequently, obscures makeup cell-of-origin. The cell somehow “neomorphic” cell, biologic properties are tightly dependent upon level EWSR1-FLI1. When harbors low EWSR1-FLI1, it loses this neomorphic identity retrieve cell-of-origin, mesenchymal phenotype. This leads us propose new model phenotypic plasticity whereby dynamic fluctuation dominant oncogene an intrinsic characteristic oncogenic potential. causes fluctuations presently unknown. They may be partly stochastic as they observed in lines vitro but also signals surrounding microenvironment. situation very different neuroblastoma where blueprint frequently noradrenergic progenitor, can clearly detected whatever abnormalities cells. Our recent data nevertheless suggest that exhibit some transition between states witness identities. conclusion, cancers constitute simplified systems investigate relative interdependent contributions nongenetic factors document shifts. Citation Format: Olivier Delattre, G.A. Franzetti, K. Laud-Duval, A. Brisac, Valentina Boeva, Caroline Louis-Brennetot, Agathe Peltier, Simon Durand, Cecile Pierre-Eugene, Didier Surdez, Eve Lapouble, Gaelle Pierron, Sandrine Grossetete-Lalami, Isabelle Janoueix-Lerosey. Identity shifts [abstract]. In: Proceedings AACR Special Conference: Pediatric Cancer Research: From Basic Science Clinic; 2017 Dec 3-6; Atlanta, Georgia. Philadelphia (PA): AACR; Res 2018;78(19 Suppl):Abstract nr IA02.