This may indicate that loss of SETD2 is a strong driver of epigenome deregulation that directs tumor cells down a distinct pathway, whereas SETD2 proficient tumor cells sustain greater variability in the epigenome due to diversity of other genetic changes that may work only partly through the epigenome (e.g., VHL [49]) and/or epigenome-independent pathways. Here, VHL is linked to neoplasm.