1:Centro Nacional de Investigaciones Oncológicas

The epigenome is highly deregulated in cancer and, as it consists of reversible modifications at the cellular DNA level, it is considered an attractive therapeutic target. Childhood cancers are characterized by lower mutagenic profiles than adult cancers. Few mutations drive malignant transformation. The paediatric tumour Ewing's Sarcoma (ES) is characterized by the EWSR1/FLI1 fusion gene, as a consequence of the translocation t(11;22) (q24;q12).  Its product acts as a transcription modulator that has been shown to be a key player in the dysregulation of the epigenome of these neoplastic cells. We hypothesized that high-throughput CRISPR targeting of epigenetic regulators will enable us to define a set of genes that are essential to ES tumorogenicity. We have identified genes whose absence inhibits cell proliferation of ES-derived cell lines. This approach allows the identification of possible candidates that could be targetable to inhibit tumor progression.