DICER1 and DICER1-related tumor predisposition: Somatic hotspot mutations affecting the RNase IIIb domain of DICER1 impair processing of 5p miRNAs (those derived from the 5′-arm of the pre-miRNA hairpin) (129) and are often found as “second hit” mutations that act in tandem with DICER1 germline mutations to induce Wilms tumorigenesis in DICER1 syndrome (a disorder that increases susceptibility to a variety of tumors) (130–132).