Cancer Proliferation Gene Discovery Through Functional Genomics

• Published in: Science (American Association for the Advancement of Science) Vol. 319; no. 5863; pp. 620 - 624
• Main Authors: Schlabach, Michael R, Luo, Ji, Solimini, Nicole L, Hu, Guang, Xu, Qikai, Li, Mamie Z, Zhao, Zhenming, Smogorzewska, Agata, Sowa, Mathew E, Ang, Xiaolu L, Westbrook, Thomas F, Liang, Anthony C, Chang, Kenneth, Hackett, Jennifer A, Harper, J. Wade, Hannon, Gregory J, Elledge, Stephen J
• Format: Journal Article
• Language: English
• Published: Washington, DC American Association for the Advancement of Science 01.02.2008; The American Association for the Advancement of Science
• Subjects: Bar codes; Biological and medical sciences; Breast Neoplasms - genetics; Breast Neoplasms - pathology; Cancer; Cell cycle; Cell growth; Cell Line; Cell Line, Tumor; Cell lines; Cell Proliferation; Cell Survival - genetics; Cellular biology; Colonic Neoplasms - genetics; Colonic Neoplasms - pathology; Gene Library; Genes, Neoplasm; Genetic screening; Genetic Vectors; Genome, Human; Genomics; Genomics - methods; Genotype & phenotype; HCT116 cells; Humans; Medical sciences; MicroRNAs; Multiple tumors. Solid tumors. Tumors in childhood (general aspects); Oligonucleotide Array Sequence Analysis; Retroviridae - genetics; Ribonucleic acid; RNA; RNA, Small Interfering; School dropouts; Small interfering RNA; Stem cells; Tumors; Viability; Human; Multiplexing; Cell proliferation; Phenotype; Cancerology; Gene; Investigation method; Genomics; Genetics; Malignant tumor; Short hairpin RNA; Cancer
• ISSN: 0036-8075; 1095-9203
• DOI: 10.1126/science.1149200

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.