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 Cambronne, 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

299 Citations (Scopus)

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
Externally publishedYes

Fingerprint

Neoplasm Genes
Genetic Association Studies
Genomics
Neoplasms
Genome
Cell Cycle Proteins
Atlases
Protein Biosynthesis
Small Interfering RNA
Cell Survival
Cell Proliferation
Phenotype
Costs and Cost Analysis
Cell Line
Genes

ASJC Scopus subject areas

  • Medicine(all)
  • General

Cite this

Schlabach, M. R., Luo, J., Solimini, N. L., Hu, G., Xu, Q., Li, M. Z., ... Elledge, S. J. (2008). Cancer proliferation gene discovery through functional genomics. Science, 319(5863), 620-624. https://doi.org/10.1126/science.1149200

Cancer proliferation gene discovery through functional genomics. / Schlabach, Michael R.; Luo, Ji; Solimini, Nicole L.; Hu, Guang; Xu, Qikai; Li, Mamie Z.; Zhao, Zhenming; Smogorzewska, Agata; Sowa, Mathew E.; Cambronne, Xiaolu; Westbrook, Thomas F.; Liang, Anthony C.; Chang, Kenneth; Hackett, Jennifer A.; Harper, J. Wade; Hannon, Gregory J.; Elledge, Stephen J.

In: Science, Vol. 319, No. 5863, 01.02.2008, p. 620-624.

Research output: Contribution to journalArticle

Schlabach, MR, Luo, J, Solimini, NL, Hu, G, Xu, Q, Li, MZ, Zhao, Z, Smogorzewska, A, Sowa, ME, Cambronne, X, Westbrook, TF, Liang, AC, Chang, K, Hackett, JA, Harper, JW, Hannon, GJ & Elledge, SJ 2008, 'Cancer proliferation gene discovery through functional genomics', Science, vol. 319, no. 5863, pp. 620-624. https://doi.org/10.1126/science.1149200
Schlabach MR, Luo J, Solimini NL, Hu G, Xu Q, Li MZ et al. Cancer proliferation gene discovery through functional genomics. Science. 2008 Feb 1;319(5863):620-624. https://doi.org/10.1126/science.1149200
Schlabach, Michael R. ; Luo, Ji ; Solimini, Nicole L. ; Hu, Guang ; Xu, Qikai ; Li, Mamie Z. ; Zhao, Zhenming ; Smogorzewska, Agata ; Sowa, Mathew E. ; Cambronne, Xiaolu ; Westbrook, Thomas F. ; Liang, Anthony C. ; Chang, Kenneth ; Hackett, Jennifer A. ; Harper, J. Wade ; Hannon, Gregory J. ; Elledge, Stephen J. / Cancer proliferation gene discovery through functional genomics. In: Science. 2008 ; Vol. 319, No. 5863. pp. 620-624.
@article{c0f76a9a5f1e4bc2b65f905099b3751e,
title = "Cancer proliferation gene discovery through functional genomics",
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.",
author = "Schlabach, {Michael R.} and Ji Luo and Solimini, {Nicole L.} and Guang Hu and Qikai Xu and Li, {Mamie Z.} and Zhenming Zhao and Agata Smogorzewska and Sowa, {Mathew E.} and Xiaolu Cambronne and Westbrook, {Thomas F.} and Liang, {Anthony C.} and Kenneth Chang and Hackett, {Jennifer A.} and Harper, {J. Wade} and Hannon, {Gregory J.} and Elledge, {Stephen J.}",
year = "2008",
month = "2",
day = "1",
doi = "10.1126/science.1149200",
language = "English (US)",
volume = "319",
pages = "620--624",
journal = "Science",
issn = "0036-8075",
publisher = "American Association for the Advancement of Science",
number = "5863",

}

TY - JOUR

T1 - Cancer proliferation gene discovery through functional genomics

AU - Schlabach, Michael R.

AU - Luo, Ji

AU - Solimini, Nicole L.

AU - Hu, Guang

AU - Xu, Qikai

AU - Li, Mamie Z.

AU - Zhao, Zhenming

AU - Smogorzewska, Agata

AU - Sowa, Mathew E.

AU - Cambronne, Xiaolu

AU - Westbrook, Thomas F.

AU - Liang, Anthony C.

AU - Chang, Kenneth

AU - Hackett, Jennifer A.

AU - Harper, J. Wade

AU - Hannon, Gregory J.

AU - Elledge, Stephen J.

PY - 2008/2/1

Y1 - 2008/2/1

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=38849098442&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=38849098442&partnerID=8YFLogxK

U2 - 10.1126/science.1149200

DO - 10.1126/science.1149200

M3 - Article

VL - 319

SP - 620

EP - 624

JO - Science

JF - Science

SN - 0036-8075

IS - 5863

ER -