Quantitative and qualitative regulation of gene expression by FET oncogenic fusions

Gene fusions involving FET (FUS, EWSR1 and TAF15) genes encode for potent oncoproteins that act as driver transcription factors in multiple sarcomas and leukemias. While these fusions have mostly been studied in the context of transcriptional regulation, evidence suggest they could carry post-transcriptional functions. In this project, we highlighted that FET fusions remodel the transcriptional landscape of the cells both quantitatively and qualitatively by altering alternative splicing patterns. We have further shown that this role is independent of their upstream transcriptional activities, thus suggesting that this novel oncogenic function may be direct and lead to promising therapeutic opportunities.