PRC2-Inactivating Mutations in Cancer Enhance Cytotoxic Response to DNMT1-Targeted Therapy via Enhanced Viral Mimicry

PRC2 inactivation in malignant peripheral nerve sheath tumors and melanoma potentiates DNMT1 inhibitor–mediated derepression of retrotransposons, which leads to increased immune pathway signaling and cell death through the double-stranded RNA sensor PKR.