Cancer proliferation gene discovery through functional genomics

Michael R. Schlabach, Ji Luo, Nicole L. Solimini, Guang Hu, Qikai Xu, Mamie Z. Li, Zhenming Zhao, Agata Smogorzewska, Mathew E. Sowa, Xiaolu L. Ang, Thomas F. Westbrook, Anthony C. Liang, Kenneth Chang, Jennifer A. Hackett, J. Wade Harper, Gregory J. Hannon, Stephen J. Elledge

Research output: Contribution to journalArticle

308 Scopus citations

Abstract

Retroviral short hairpin RNA (shRNA)-mediated genetic screens in mammalian cells are powerful tools for discovering loss-of-function phenotypes. We describe a highly parallel multiplex methodology for screening large pools of shRNAs using half-hairpin barcodes for microarray deconvolution. We carried out dropout screens for shRNAs that affect cell proliferation and viability in cancer cells and normal cells. We identified many shRNAs to be antiproliferative that target core cellular processes, such as the cell cycle and protein translation, in all cells examined. Moreover, we identified genes that are selectively required for proliferation and survival in different cell lines. Our platform enables rapid and cost-effective genome-wide screens to identify cancer proliferation and survival genes for target discovery. Such efforts are complementary to the Cancer Genome Atlas and provide an alternative functional view of cancer cells.

Original languageEnglish (US)
Pages (from-to)620-624
Number of pages5
JournalScience
Volume319
Issue number5863
DOIs
StatePublished - Feb 1 2008

ASJC Scopus subject areas

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    Schlabach, M. R., Luo, J., Solimini, N. L., Hu, G., Xu, Q., Li, M. Z., Zhao, Z., Smogorzewska, A., Sowa, M. E., Ang, X. L., Westbrook, T. F., Liang, A. C., Chang, K., Hackett, J. A., Harper, J. W., Hannon, G. J., & Elledge, S. J. (2008). Cancer proliferation gene discovery through functional genomics. Science, 319(5863), 620-624. https://doi.org/10.1126/science.1149200