More recently, analysis of cancers associated with DICER1 syndrome as well as other early childhood cancers (e.g., Wilms tumor) led to the identification of a peculiar pattern of somatic second-hit mutations in DICER1 and DROSHA. These mostly missense mutations are not randomly distributed over the genes but form clear hotspots, mostly affecting few amino acid residues located in or adjacent to metal-ion-binding residues in the RNaseIIIb domain of either DICER1 (D1709, E1813) or DROSHA (E1147, D1151) [63–68]. Here, DICER1 is linked to DICER1-related tumor predisposition.