Cancer-associated recurrent mutations in RNase III domains of DICER1

Abstract

Biallelic somatic mutations in the RNase IIIb domain of DICER1 are recurrent in different cancer types, disrupting the processing of the 5p, but not 3p, strand of the pre-miRNAs. Using data from the Cancer Genome Atlas project, we showed these mutations cause 5p-strand miRNA depletion, which in turn causes up-regulation of targets of particular miRNA families in human tumors. Furthermore, we identified a previously unknown re-current mutation in the RNase IIIa domain that also disrupts 5p-strand processing.