H2BC21 and neoplasm: Liu et al. (2007) reported that H2AFX may serve as a tumor suppressor protein, and its upregulation sensitizes the gastrointestinal stromal tumor cells to imatinib chemotherapeutic drug treatment. Nevertheless, downregulation of H2AFX may also indicate genomic instability in cells exposed to external stimuli. Supportively, Braunstein et al. (2016) revealed that breast cancer cells with downregulated H2A and H2B were more sensitive toward anthracycline-induced apoptosis.