title: Essential gene profiles in breast, pancreatic, and ovarian cancer cells.
abstract: Genomic analyses are yielding a host of new information on the multiple genetic abnormalities associated with specific types of cancer. A comprehensive description of cancer-associated genetic abnormalities can improve our ability to classify tumors into clinically relevant subgroups and, on occasion, identify mutant genes that drive the cancer phenotype ("drivers"). More often, though, the functional significance of cancer-associated mutations is difficult to discern. Genome-wide pooled short hairpin RNA (shRNA) screens enable global identification of the genes essential for cancer cell survival and proliferation, providing a "functional genomic" map of human cancer to complement genomic studies. Using a lentiviral shRNA library targeting ~16,000 genes and a newly developed, dynamic scoring approach, we identified essential gene profiles in 72 breast, pancreatic, and ovarian cancer cell lines. Integrating our results with current and future genomic data should facilitate the systematic identification of drivers, unanticipated synthetic lethal relationships, and functional vulnerabilities of these tumor types.
  
  
  CONCLUSIONS
  This study presents a resource of genome-scale, pooled shRNA screens for 72 breast, pancreatic, and ovarian cancer cell lines that will serve as a functional complement to genomics data, facilitate construction of essential gene profiles, help uncover synthetic lethal relationships, and identify uncharacterized genetic vulnerabilities in these tumor types.
  
  
  CONCLUSIONS
  This study presents a resource of genome-scale, pooled shRNA screens for 72 breast, pancreatic, and ovarian cancer cell lines that will serve as a functional complement to genomics data, facilitate construction of essential gene profiles, help uncover synthetic lethal relationships, and identify uncharacterized genetic vulnerabilities in these tumor types.
authors.affiliation: Campbell Family Cancer Research Institute, Ontario Cancer Institute, Princess Margaret Hospital University Health Network, Toronto, Canada.
authors.forename: Richard
authors.initials: R
authors.lastname: Marcotte
authors.affiliation: Donnelly Centre and Banting & Best Department of Medical Research, University of Toronto, Toronto, Canada.|Ontario Institute for Cancer Research, Toronto, Canada.
authors.forename: Kevin R
authors.initials: KR
authors.lastname: Brown
authors.affiliation: Campbell Family Cancer Research Institute, Ontario Cancer Institute, Princess Margaret Hospital University Health Network, Toronto, Canada.
authors.forename: Fernando
authors.initials: F
authors.lastname: Suarez
authors.affiliation: Donnelly Centre and Banting & Best Department of Medical Research, University of Toronto, Toronto, Canada.
authors.forename: Azin
authors.initials: A
authors.lastname: Sayad
authors.affiliation: Donnelly Centre and Banting & Best Department of Medical Research, University of Toronto, Toronto, Canada.
authors.forename: Konstantina
authors.initials: K
authors.lastname: Karamboulas
authors.affiliation: Campbell Family Cancer Research Institute, Ontario Cancer Institute, Princess Margaret Hospital University Health Network, Toronto, Canada.
authors.forename: Paul M
authors.initials: PM
authors.lastname: Krzyzanowski
authors.affiliation: Campbell Family Cancer Research Institute, Ontario Cancer Institute, Princess Margaret Hospital University Health Network, Toronto, Canada.
authors.forename: Fabrice
authors.initials: F
authors.lastname: Sircoulomb
authors.affiliation: Department of Medical Biophysics, University of Toronto, Toronto, Canada.|Campbell Family Cancer Research Institute, Ontario Cancer Institute, Princess Margaret Hospital University Health Network, Toronto, Canada.
authors.forename: Mauricio
authors.initials: M
authors.lastname: Medrano
authors.affiliation: Donnelly Centre and Banting & Best Department of Medical Research, University of Toronto, Toronto, Canada.
authors.forename: Yaroslav
authors.initials: Y
authors.lastname: Fedyshyn
authors.affiliation: Donnelly Centre and Banting & Best Department of Medical Research, University of Toronto, Toronto, Canada.|Ontario Institute for Cancer Research, Toronto, Canada.
authors.forename: Judice L Y
authors.initials: JLY
authors.lastname: Koh
authors.affiliation: Donnelly Centre and Banting & Best Department of Medical Research, University of Toronto, Toronto, Canada.
authors.forename: Dewald
authors.initials: D
authors.lastname: van Dyk
authors.affiliation: Donnelly Centre and Banting & Best Department of Medical Research, University of Toronto, Toronto, Canada.
authors.forename: Bodhana
authors.initials: B
authors.lastname: Fedyshyn
authors.affiliation: Donnelly Centre and Banting & Best Department of Medical Research, University of Toronto, Toronto, Canada.
authors.forename: Marianna
authors.initials: M
authors.lastname: Luhova
authors.affiliation: Ontario Institute for Cancer Research, Toronto, Canada.
authors.forename: Glauber C
authors.initials: GC
authors.lastname: Brito
authors.affiliation: Donnelly Centre and Banting & Best Department of Medical Research, University of Toronto, Toronto, Canada.
authors.forename: Franco J
authors.initials: FJ
authors.lastname: Vizeacoumar
authors.affiliation: Samuel Lunenfeld Research Institute, Toronto, Canada.
authors.forename: Frederick S
authors.initials: FS
authors.lastname: Vizeacoumar
authors.affiliation: Samuel Lunenfeld Research Institute, Toronto, Canada.|Department of Experimental Medicine and Biochemical Sciences, University of Perugia, Perugia, Italy.
authors.forename: Alessandro
authors.initials: A
authors.lastname: Datti
authors.affiliation: Donnelly Centre and Banting & Best Department of Medical Research, University of Toronto, Toronto, Canada.
authors.forename: Dahlia
authors.initials: D
authors.lastname: Kasimer
authors.affiliation: Donnelly Centre and Banting & Best Department of Medical Research, University of Toronto, Toronto, Canada.
authors.forename: Alla
authors.initials: A
authors.lastname: Buzina
authors.affiliation: Donnelly Centre and Banting & Best Department of Medical Research, University of Toronto, Toronto, Canada.
authors.forename: Patricia
authors.initials: P
authors.lastname: Mero
authors.affiliation: Donnelly Centre and Banting & Best Department of Medical Research, University of Toronto, Toronto, Canada.
authors.forename: Christine
authors.initials: C
authors.lastname: Misquitta
authors.affiliation: Campbell Family Cancer Research Institute, Ontario Cancer Institute, Princess Margaret Hospital University Health Network, Toronto, Canada.
authors.forename: Josee
authors.initials: J
authors.lastname: Normand
authors.affiliation: Campbell Family Cancer Research Institute, Ontario Cancer Institute, Princess Margaret Hospital University Health Network, Toronto, Canada.
authors.forename: Maliha
authors.initials: M
authors.lastname: Haider
authors.affiliation: Donnelly Centre and Banting & Best Department of Medical Research, University of Toronto, Toronto, Canada.|Ontario Institute for Cancer Research, Toronto, Canada.
authors.forename: Troy
authors.initials: T
authors.lastname: Ketela
authors.affiliation: Department of Molecular Genetics, University of Toronto, Toronto, Canada.|Samuel Lunenfeld Research Institute, Toronto, Canada.
authors.forename: Jeffrey L
authors.initials: JL
authors.lastname: Wrana
authors.affiliation: Department of Medical Biophysics, University of Toronto, Toronto, Canada.|Campbell Family Cancer Research Institute, Ontario Cancer Institute, Princess Margaret Hospital University Health Network, Toronto, Canada.|Ontario Institute for Cancer Research, Toronto, Canada.
authors.forename: Robert
authors.initials: R
authors.lastname: Rottapel
authors.affiliation: Department of Medical Biophysics, University of Toronto, Toronto, Canada.|Campbell Family Cancer Research Institute, Ontario Cancer Institute, Princess Margaret Hospital University Health Network, Toronto, Canada.
authors.forename: Benjamin G
authors.initials: BG
authors.lastname: Neel
authors.affiliation: Donnelly Centre and Banting & Best Department of Medical Research, University of Toronto, Toronto, Canada.|Department of Molecular Genetics, University of Toronto, Toronto, Canada.
authors.forename: Jason
authors.initials: J
authors.lastname: Moffat
mesh_terms: D001943:Breast Neoplasms / Q000235:genetics* / Q000378:metabolism; D045744:Cell Line, Tumor; D005260:Female; D015723:Gene Library; D006801:Humans; D008297:Male; D010051:Ovarian Neoplasms / Q000235:genetics* / Q000378:metabolism; D010190:Pancreatic Neoplasms / Q000235:genetics* / Q000378:metabolism; D034741:RNA, Small Interfering / Q000235:genetics / Q000378:metabolism; D059467:Transcriptome
chemical_list: D034741:RNA, Small Interfering