DICER1-associated tumors typically harbor a germline loss-of-function (LOF) variant (nonsense, frame-shift, rarely missense; copy number changes are rarely observed) and a tumor-specific missense mutation in the DICER1 RNase IIIb domain affecting one of the five hotspot codons that encode key amino acids in the metal biding catalytic cleft of the nuclease domain: E1705, D1709, G1809, D1810, and E1813 (8–11). The gene discussed is DICER1; the disease is neoplasm.