POLE and cancer: This variant had been previously reported in three unrelated families diagnosed with melanoma at ages 22–73 and other tumors, including breast cancer, squamous cell carcinoma, and non-Hodgkin lymphoma,10,33 and in a patient with a Lynch syndrome–associated MLH1-deficient colorectal tumor (Supplementary Table S5).34 Of the 13 studied cancer-affected individuals (in this and previous reports) only 7 carried POLE c.861T>A.