The 9p21.3 locus encompasses multiple key tumor-suppressor genes (TSGs): the cell cycle inhibitors CDKN2A (encoding p16INK4a and p14ARF) and CDKN2B (encoding p15INK4b), which collectively activate the major tumor-suppressive pathways p53 and RB17–19. The gene discussed is CDKN2A; the disease is neoplasm.