title: A CRISPR/Cas9 Functional Screen Identifies Rare Tumor Suppressors.
abstract: An enormous amount of tumor sequencing data has been generated through large scale sequencing efforts. The functional consequences of the majority of mutations identified by such projects remain an open, unexplored question. This problem is particularly complicated in the case of rare mutations where frequency of occurrence alone or prediction of functional consequences are insufficient to distinguish driver from passenger or bystander mutations. We combine genome editing technology with a powerful mouse cancer model to uncover previously unsuspected rare oncogenic mutations in Burkitt's lymphoma. We identify two candidate tumor suppressors whose loss cooperate with MYC over-expression to accelerate lymphomagenesis. Our results highlight the utility of in vivo CRISPR/Cas9 screens combined with powerful mouse models to identify and validate rare oncogenic modifier events from tumor mutational data.
authors.affiliation: Department of Biochemistry, McIntyre Medical Sciences Building, McGill University, Montreal, Québec, H3G 1Y6, Canada.
authors.forename: Alexandra
authors.initials: A
authors.lastname: Katigbak
authors.affiliation: Department of Biochemistry, McIntyre Medical Sciences Building, McGill University, Montreal, Québec, H3G 1Y6, Canada.
authors.forename: Regina
authors.initials: R
authors.lastname: Cencic
authors.affiliation: Department of Biochemistry, McIntyre Medical Sciences Building, McGill University, Montreal, Québec, H3G 1Y6, Canada.
authors.forename: Francis
authors.initials: F
authors.lastname: Robert
authors.affiliation: Department of Biochemistry, McIntyre Medical Sciences Building, McGill University, Montreal, Québec, H3G 1Y6, Canada.
authors.forename: Patrick
authors.initials: P
authors.lastname: Sénécha
authors.affiliation: Institute for Cancer Genetics, Columbia University Medical Center, 1130 St Nicholas Ave, New York, NY 10032, USA.
authors.forename: Claudio
authors.initials: C
authors.lastname: Scuoppo
authors.affiliation: Department of Biochemistry, McIntyre Medical Sciences Building, McGill University, Montreal, Québec, H3G 1Y6, Canada.|The Rosalind and Morris Goodman Cancer Research Center, 1160 Avenue des Pins, Montreal, Québec, H3A 1A3, Canada.|Dept of Oncology, 546 Pine Ave. West, Montreal, Québec, H2W 1S6, Canada.
authors.forename: Jerry
authors.initials: J
authors.lastname: Pelletier
mesh_terms: D000818:Animals; D002051:Burkitt Lymphoma / Q000235:genetics*; D064113:CRISPR-Cas Systems; D002471:Cell Transformation, Neoplastic / Q000235:genetics*; D005260:Female; D016147:Genes, Tumor Suppressor; D051379:Mice