RT Journal Article
SR Electronic
T1 Cancer-associated recurrent mutations in RNase III domains of DICER1
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 005686
DO 10.1101/005686
A1 Bülent Arman Aksoy
A1 Anders Jacobsen
A1 Robert J. Fieldhouse
A1 William Lee
A1 Emek Demir
A1 Giovanni Ciriello
A1 Nikolaus Schultz
A1 Debora S. Marks
A1 Chris Sander
YR 2014
UL http://biorxiv.org/content/early/2014/09/12/005686.abstract
AB 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.