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

Bric, A., Miething, C., Bialucha, C. U., Scuoppo, C., Zender, L., Krasnitz, A., Xuan, Z., Zuber, J., Wigler, M. H., Hicks, J. B., McCombie, W. R., Hemann, M. T., Hannon, G. J., Powers, S., Lowe, S. W. (October 2009) Functional identification of tumor-suppressor genes through an in vivo RNA interference screen in a mouse lymphoma model. Cancer Cell, 16 (4). pp. 324-35. ISSN 1535-6108

URL: http://www.ncbi.nlm.nih.gov/pubmed/19800577

DOI: 10.1016/j.ccr.2009.08.015

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.

Item Type:	Paper
Uncontrolled Keywords:	Angiopoietin 2 genetics Animals Cell Cycle Proteins genetics Cell Line Tumor Cell Transformation Neoplastic genetics metabolism pathology DNA Damage Gene Expression Regulation Neoplastic Genes Tumor Suppressor Genes myc Genes p53 Genetic Screening methods Hematopoietic Stem Cell Transplantation Hematopoietic Stem Cells metabolism Humans Intercellular Signaling Peptides and Proteins genetics Lymphoma genetics metabolism pathology MAP Kinase Kinase 1 genetics Map Membrane Proteins genetics Mice Mice Inbred C57BL Nerve Tissue Proteins genetics Prognosis RNA Interference RNAi Reproducibility of Results Time Factors Transduction Genetic
Subjects:	diseases & disorders > cancer bioinformatics > genomics and proteomics > genetics & nucleic acid processing > DNA, RNA structure, function, modification > RNAi bioinformatics > genomics and proteomics > genetics & nucleic acid processing > DNA, RNA structure, function, modification > shRNA
CSHL Authors:	Bialucha, Carl Uli Bric, Anka Hannon, Gregory J. Hicks, James B. Krasnitz, Alexander Lowe, Scott W. McCombie, W. Richard Miething, Cornelius Powers, Scott Scuoppo, Claudio Wigler, Michael H. Xuan, Zhenyu Y. Zender, Lars Zuber, Johannes
Communities:	CSHL labs > Hannon lab CSHL labs > Hicks lab CSHL labs > Krasnitz lab CSHL labs > Lowe lab CSHL labs > McCombie lab CSHL labs > Powers lab CSHL labs > Wigler lab CSHL Cancer Center Shared Resources > Animal Services CSHL Cancer Center Shared Resources > Antibody and Phage Display Service CSHL Cancer Center Shared Resources > Bioinformatics Service School of Biological Sciences > Publications CSHL Cancer Center Shared Resources > DNA Sequencing Service CSHL Cancer Center Shared Resources > Flow Cytometry Service CSHL Cancer Center Shared Resources > Gene Targeting Service CSHL Cancer Center Shared Resources > Instrumentation Service CSHL Cancer Center Shared Resources > Microscopy Service
Depositing User:	Editor Margaret Fantz
Date:	6 October 2009
Date Deposited:	08 May 2012 17:46
Last Modified:	30 Dec 2014 16:04
PMCID:	PMC2829755
Related URLs:	Publisher
URI:	https://repository.cshl.edu/id/eprint/26052

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