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1: Science. 2008 Feb 1;319(5863):620-4.
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Erratum in:
  • Science.2008 Apr 18;320(5874):316.

Cancer proliferation gene discovery through functional genomics.

Schlabach MR, Luo J, Solimini NL, Hu G, Xu Q, Li MZ, Zhao Z, Smogorzewska A, Sowa ME, Ang XL, Westbrook TF, Liang AC, Chang K, Hackett JA, Harper JW, Hannon GJ, Elledge SJ.

Howard Hughes Medical Institute and Department of Genetics, Center for Genetics and Genomics, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115, USA.

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.

Publication Types:
PMID: 18239126 [PubMed - indexed for MEDLINE]