A novel retinoblastoma therapy from genomic and epigenetic analyses

摘要: Retinoblastoma is an aggressive childhood cancer of the developing retina that initiated by biallelic loss RB1. Tumours progress very quickly following RB1 inactivation but underlying mechanism not known. Here we show retinoblastoma genome stable, multiple pathways can be epigenetically deregulated. To identify mutations cooperate with loss, performed whole-genome sequencing retinoblastomas. The overall mutational rate was low; only known gene mutated. We then evaluated role in stability and considered non-genetic mechanisms pathway deregulation. For example, proto-oncogene SYK upregulated required for tumour cell survival. Targeting a small-molecule inhibitor induced death vitro vivo. Thus, retinoblastomas may develop as result epigenetic deregulation key direct or indirect loss.