Recurrent somatic DICER1 mutations in nonepithelial ovarian cancers.
Abstract | BACKGROUND: METHODS: We sequenced the whole transcriptomes or exomes of 14 nonepithelial ovarian tumors and noted closely clustered mutations in the region of DICER1 encoding the RNase IIIb domain of DICER1 in four samples. We then sequenced this region of DICER1 in additional ovarian tumors and in certain other tumors and queried the effect of the mutations on the enzymatic activity of DICER1 using in vitro RNA cleavage assays. RESULTS: CONCLUSIONS: Somatic missense mutations affecting the RNase IIIb domain of DICER1 are common in nonepithelial ovarian tumors. These mutations do not obliterate DICER1 function but alter it in specific cell types, a novel mechanism through which perturbation of microRNA processing may be oncogenic. (Funded by the Terry Fox Research Institute and others.).
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Authors | Alireza Heravi-Moussavi, Michael S Anglesio, S-W Grace Cheng, Janine Senz, Winnie Yang, Leah Prentice, Anthony P Fejes, Christine Chow, Alicia Tone, Steve E Kalloger, Nancy Hamel, Andrew Roth, Gavin Ha, Adrian N C Wan, Sarah Maines-Bandiera, Clara Salamanca, Barbara Pasini, Blaise A Clarke, Anna F Lee, Cheng-Han Lee, Chengquan Zhao, Robert H Young, Samuel A Aparicio, Poul H B Sorensen, Michelle M M Woo, Niki Boyd, Steven J M Jones, Martin Hirst, Marco A Marra, Blake Gilks, Sohrab P Shah, William D Foulkes, Gregg B Morin, David G Huntsman |
Journal | The New England journal of medicine
(N Engl J Med)
Vol. 366
Issue 3
Pg. 234-42
(Jan 19 2012)
ISSN: 1533-4406 [Electronic] United States |
PMID | 22187960
(Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)
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Chemical References |
- MicroRNAs
- DICER1 protein, human
- Ribonuclease III
- DEAD-box RNA Helicases
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Topics |
- Carcinosarcoma
(genetics)
- DEAD-box RNA Helicases
(genetics)
- Female
- Gene Expression
- Gene Expression Profiling
- Germ-Line Mutation
- Humans
- MicroRNAs
(metabolism)
- Mutation, Missense
- Neoplasms, Germ Cell and Embryonal
(genetics)
- Ovarian Neoplasms
(genetics)
- Rhabdomyosarcoma
(genetics)
- Ribonuclease III
(genetics)
- Sequence Analysis, DNA
- Sertoli-Leydig Cell Tumor
(genetics)
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