title: A genetic network that suppresses genome rearrangements in Saccharomyces cerevisiae and contains defects in cancers.
abstract: Gross chromosomal rearrangements (GCRs) play an important role in human diseases, including cancer. The identity of all Genome Instability Suppressing (GIS) genes is not currently known. Here multiple Saccharomyces cerevisiae GCR assays and query mutations were crossed into arrays of mutants to identify progeny with increased GCR rates. One hundred eighty two GIS genes were identified that suppressed GCR formation. Another 438 cooperatively acting GIS genes were identified that were not GIS genes, but suppressed the increased genome instability caused by individual query mutations. Analysis of TCGA data using the human genes predicted to act in GIS pathways revealed that a minimum of 93% of ovarian and 66% of colorectal cancer cases had defects affecting one or more predicted GIS gene. These defects included loss-of-function mutations, copy-number changes associated with reduced expression, and silencing. In contrast, acute myeloid leukaemia cases did not appear to have defects affecting the predicted GIS genes.
authors.affiliation: Ludwig Institute for Cancer Res., University of California School of Medicine, San Diego, 9500 Gilman Drive, La Jolla, California 92093-0669, USA.|Department of Medicine, University of California School of Medicine, San Diego, 9500 Gilman Drive, La Jolla, California 92093-0669, USA.
authors.forename: Christopher D
authors.initials: CD
authors.lastname: Putnam
authors.affiliation: Ludwig Institute for Cancer Res., University of California School of Medicine, San Diego, 9500 Gilman Drive, La Jolla, California 92093-0669, USA.
authors.forename: Anjana
authors.initials: A
authors.lastname: Srivatsan
authors.affiliation: Ludwig Institute for Cancer Res., University of California School of Medicine, San Diego, 9500 Gilman Drive, La Jolla, California 92093-0669, USA.
authors.forename: Rahul V
authors.initials: RV
authors.lastname: Nene
authors.affiliation: Ludwig Institute for Cancer Res., University of California School of Medicine, San Diego, 9500 Gilman Drive, La Jolla, California 92093-0669, USA.
authors.forename: Sandra L
authors.initials: SL
authors.lastname: Martinez
authors.affiliation: Ludwig Institute for Cancer Res., University of California School of Medicine, San Diego, 9500 Gilman Drive, La Jolla, California 92093-0669, USA.
authors.forename: Sarah P
authors.initials: SP
authors.lastname: Clotfelter
authors.affiliation: Ludwig Institute for Cancer Res., University of California School of Medicine, San Diego, 9500 Gilman Drive, La Jolla, California 92093-0669, USA.
authors.forename: Sara N
authors.initials: SN
authors.lastname: Bell
authors.affiliation: Ludwig Institute for Cancer Res., University of California School of Medicine, San Diego, 9500 Gilman Drive, La Jolla, California 92093-0669, USA.
authors.forename: Steven B
authors.initials: SB
authors.lastname: Somach
authors.affiliation: Instituto de Bioinformática e Biotecnologia, Natal 59082-180, Brazil.|Instituto Metrópole Digital, UFRN, Natal 59082-180, Brazil.
authors.forename: Jorge E S
authors.initials: JE
authors.lastname: de Souza
authors.affiliation: Instituto do Cérebro, UFRN, Natal 59082-180, Brazil.
authors.forename: André F
authors.initials: AF
authors.lastname: Fonseca
authors.affiliation: Instituto do Cérebro, UFRN, Natal 59082-180, Brazil.
authors.forename: Sandro J
authors.initials: SJ
authors.lastname: de Souza
authors.affiliation: Ludwig Institute for Cancer Res., University of California School of Medicine, San Diego, 9500 Gilman Drive, La Jolla, California 92093-0669, USA.|Department of Cellular and Molecular Medicine, University of California School of Medicine, San Diego, 9500 Gilman Drive, La Jolla, California 92093-0669, USA.|Moores-UCSD Cancer Center, University of California School of Medicine, San Diego, 9500 Gilman Drive, La Jolla, California 92093-0669, USA.|Institute of Genomic Medicine, University of California School of Medicine, San Diego, 9500 Gilman Drive, La Jolla, California 92093-0669, USA.
authors.forename: Richard D
authors.initials: RD
authors.lastname: Kolodner
mesh_terms: D015825:Chromosomes, Fungal / Q000235:genetics; D004742:Enhancer Elements, Genetic / Q000235:genetics; D004843:Epistasis, Genetic; D015321:Gene Rearrangement / Q000235:genetics*; D053263:Gene Regulatory Networks; D005800:Genes, Fungal; D016681:Genome, Fungal; D042822:Genomic Instability; D006801:Humans; D009154:Mutation / Q000235:genetics; D009369:Neoplasms / Q000235:genetics*; D012441:Saccharomyces cerevisiae / Q000235:genetics*