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Publication : Functional identification of tumor-suppressor genes through an in vivo RNA interference screen in a mouse lymphoma model.

First Author  Bric A Year  2009
Journal  Cancer Cell Volume  16
Issue  4 Pages  324-35
PubMed ID  19800577 Mgi Jnum  J:153707
Mgi Id  MGI:4366129 Doi  10.1016/j.ccr.2009.08.015
Citation  Bric A, et al. (2009) Functional identification of tumor-suppressor genes through an in vivo RNA interference screen in a mouse lymphoma model. Cancer Cell 16(4):324-35
abstractText  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.
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