wrn gene promoters and 43 patients had unmethylated wrn promoters. irinotecan was more strongly beneficial for patients with hypermethylated wrn promoters (39.4 months survival) than for those with unmethylated wrn promoters (20.7 months survival). thus, a topoisomerase inhibitor appeared to be especially synthetically lethal with deficient wrn expression. further evaluations have also indicated synthetic lethality of deficient expression of wrn and topoisomerase inhibitors.