Functional Identification of Tumor-Suppressor Genes through an In Vivo RNA Interference Screen in a Mouse Lymphoma Model

Anka Bric, Cornelius Miething, Carl Uli Bialucha, Claudio Scuoppo, Lars Zender, Alexander Krasnitz, Zhenyu Xuan, Johannes Zuber, Michael Wigler, James Hicks, Richard W. McCombie, Michael T. Hemann, Gregory J. Hannon, Scott Powers, Scott W. Lowe

Research output: Contribution to journalArticle

132 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)324-335
Number of pages12
JournalCancer Cell
Volume16
Issue number4
DOIs
Publication statusPublished - Oct 6 2009
Externally publishedYes

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Keywords

  • CELLCYCLE

ASJC Scopus subject areas

  • Oncology
  • Cell Biology
  • Cancer Research

Cite this

Bric, A., Miething, C., Bialucha, C. U., Scuoppo, C., Zender, L., Krasnitz, A., ... Lowe, S. W. (2009). Functional Identification of Tumor-Suppressor Genes through an In Vivo RNA Interference Screen in a Mouse Lymphoma Model. Cancer Cell, 16(4), 324-335. https://doi.org/10.1016/j.ccr.2009.08.015