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Cancer-associated recurrent mutations in RNase III domains of DICER1

Bülent Arman Aksoy, Anders Jacobsen, Robert J. Fieldhouse, William Lee, Emek Demir, Giovanni Ciriello, Nikolaus Schultz, Debora S. Marks, Chris Sander
doi: https://doi.org/10.1101/005686
Bülent Arman Aksoy
1Computational Biology Center, Memorial Sloan-Kettering Cancer Center, NY, NY, 10065
2Institutional Training Program in Computational Biology & Medicine, NY, NY, 10065
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Anders Jacobsen
1Computational Biology Center, Memorial Sloan-Kettering Cancer Center, NY, NY, 10065
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Robert J. Fieldhouse
1Computational Biology Center, Memorial Sloan-Kettering Cancer Center, NY, NY, 10065
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William Lee
1Computational Biology Center, Memorial Sloan-Kettering Cancer Center, NY, NY, 10065
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Emek Demir
1Computational Biology Center, Memorial Sloan-Kettering Cancer Center, NY, NY, 10065
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Giovanni Ciriello
1Computational Biology Center, Memorial Sloan-Kettering Cancer Center, NY, NY, 10065
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Nikolaus Schultz
1Computational Biology Center, Memorial Sloan-Kettering Cancer Center, NY, NY, 10065
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Debora S. Marks
3Department of Systems Biology, Harvard Medical School, Boston, MA, 02115
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Chris Sander
1Computational Biology Center, Memorial Sloan-Kettering Cancer Center, NY, NY, 10065
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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.

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Posted May 29, 2014.
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Cancer-associated recurrent mutations in RNase III domains of DICER1
Bülent Arman Aksoy, Anders Jacobsen, Robert J. Fieldhouse, William Lee, Emek Demir, Giovanni Ciriello, Nikolaus Schultz, Debora S. Marks, Chris Sander
bioRxiv 005686; doi: https://doi.org/10.1101/005686
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Cancer-associated recurrent mutations in RNase III domains of DICER1
Bülent Arman Aksoy, Anders Jacobsen, Robert J. Fieldhouse, William Lee, Emek Demir, Giovanni Ciriello, Nikolaus Schultz, Debora S. Marks, Chris Sander
bioRxiv 005686; doi: https://doi.org/10.1101/005686

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