Transient loss of Polycomb components induces an epigenetic cancer fate

Abstract Although cancer initiation and progression are generally associated with the accumulation of somatic mutations 1,2 , substantial epigenomic alterations underlie many aspects of tumorigenesis and cancer susceptibility 3–6 , suggesting that genetic mechanisms might not be the only drivers of malignant transformation 7 . However, whether purely non-genetic mechanisms are sufficient to initiate tumorigenesis irrespective of mutations has been unknown. Here, we show that a transient perturbation of transcriptional silencing mediated by Polycomb group proteins is sufficient to induce an irreversible switch to a cancer cell fate in Drosophila . This is linked to the irreversible derepression of genes that…