TY - JOUR T1 - Cancer-associated recurrent mutations in RNase III domains of DICER1 JF - bioRxiv DO - 10.1101/005686 SP - 005686 AU - Bülent Arman Aksoy AU - Anders Jacobsen AU - Robert J. Fieldhouse AU - William Lee AU - Emek Demir AU - Giovanni Ciriello AU - Nikolaus Schultz AU - Debora S. Marks AU - Chris Sander Y1 - 2014/01/01 UR - http://biorxiv.org/content/early/2014/09/12/005686.abstract N2 - Mutations in the RNase IIIb domain of DICER1 are known to disrupt processing of 5p-strand pre-miRNAs and these mutations have previously been associated with cancer. Using data from the Cancer Genome Atlas project, we show that these mutations are recurrent across four cancer types and that a previously uncharacterized recurrent mutation in the adjacent RNase IIIa domain also disrupts 5p-strand miRNA processing. Analysis of the downstream effects of the resulting imbalance 5p/3p shows a statistically significant effect on the expression of mRNAs targeted by major conserved miRNA families. In summary, these mutations in DICER1 lead to an imbalance in miRNA strands, which has an effect on mRNA transcript levels that appear to contribute to the oncogenesis. ER -