H2BC21 and cancer: Hotspots exhibited known cancer type specificity such as H3 K27M (DMG), H3 G34R/V (pHGG), H3 K36M (HNSC, bone and cartilage tumors), and associations including H2B E76 (breast cancer, bladder cancer), H2B E35 (non-small cell lung cancer), and H3 E97 (bladder cancer) (Fig. 6d).