SETD2 and chondrosarcoma: Another mutation affecting a modification hotspot of histone H3 is the H3K36M mutation in chondrosarcoma which impairs K36 modifications by inhibition of the H3 lysine 36-specific histone methyltransferases Nuclear Receptor Binding SET Domain Protein 2 (NSD2) and SET domain containing 2 (SETD2) (Fig. 3) [61, 62].