Defects in some of the human genes identified here have been implicated in cancer (for example, BRCA1, BRCA2, ATM, BLM, REV3L and PBRM1), and some of the genes have been associated with the suppression of genome instability (for example, WRN, BLM, ATM, ATR, BRCA1 and BRCA2) or with pathways thought to act in the suppression of genome instability (for example, RAD17, RAD50, XRCC6 and TP53BP1)44, 45. The gene discussed is PBRM1; the disease is cancer.