“MPNST Epigenetics”—Response

Abstract

We thank the authors for their letter (1) and for making these points about our July 2019 Molecular Cancer Research review article (2). We acknowledge that they have provided important novel insights, with their new article (3), into a topic discussed in our review regarding potential noncanonical activities of EZH2 in malignant peripheral nerve sheath tumors (MPNST). Wassef and colleagues present compelling data revealing a marked reduction of EZH2 protein interactions occurring in the absence of SUZ12 in MPNST cells (3). Moreover, gene expression changes occurring in EZH1/2 double-knockout cells closely resemble those in SUZ12-deficient cells. Together, these data support the authors' hypothesis that EZH2 is not mutated in MPNST due to functional redundancy between EZH1 and EZH2, which would necessitate the unlikely deletion of both genes in an MPNST cell to recapit-ulate the selective advantage of SUZ12 loss. We thank the authors for pointing out their study, which was published concurrently with our review.