Functional Identification of Tumor Suppressor Genes Through an in vivo RNA Interference Screen in a Mouse Lymphoma Model
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Hemann_Functional identification.pdf
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Author(s) • • • • • • • • •
Bric, Anka
Miething, Cornelius
Bialucha, Carl Uli
Scuoppo, Claudio
Zender, Lars
Krasnitz, Alexander
Xuan, Zhenyu
Zuber, Johannes
Wigler, Michael
Hicks, James
Date Issued
October 2009
Journal
Cancer Cell
Publisher
Elsevier
Citation
Bric, Anka et al. “Functional Identification of Tumor-Suppressor Genes Through an In Vivo RNA Interference Screen in a Mouse Lymphoma Model.” Cancer Cell 16.4 (2009): 324–335.
Version
Author's final manuscript
Abstract
Short hairpin RNAs (shRNAs) capable of stably suppressing gene function by RNA interference (RNAi) can mimic tumor-suppressor-gene loss in mice. By selecting for shRNAs capable of accelerating lymphomagenesis in a well-characterized mouse lymphoma model, we identified over ten candidate tumor suppressors, including Sfrp1, Numb, Mek1, and Angiopoietin 2. Several components of the DNA damage response machinery were also identified, including Rad17, which acts as a haploinsufficient tumor suppressor that responds to oncogenic stress and whose loss is associated with poor prognosis in human patients. Our results emphasize the utility of in vivo RNAi screens, identify and validate a diverse set of tumor suppressors, and have therapeutic implications.
Description
2010 April 6
MIT Department
Massachusetts Institute of Technology. Department of Biology
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Creative Commons Attribution-Noncommercial-Share Alike 3.0
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DOI of Published Version
https://doi.org/10.1016/j.ccr.2009.08.015