title: Patterns of somatically acquired amplifications and deletions in apparently normal tissues of ovarian cancer patients.
abstract: Little is understood about the occurrence of somatic genomic alterations in normal tissues and their significance in the context of disease. Here, we identified potential somatic copy number alterations (pSCNAs) in apparently normal ovarian tissue and peripheral blood of 423 ovarian cancer patients. There were, on average, two to four pSCNAs per sample detectable at a tissue-level resolution, although some individuals had orders of magnitude more. Accordingly, we estimated the lower bound of the rate of pSCNAs per cell division. Older individuals and BRCA mutation carriers had more pSCNAs than others. pSCNAs significantly overlapped with Alu and G-quadruplexes, and the affected genes were enriched for signaling and regulation. Some of the amplification/deletion hotspots in pan-cancer genomes were hot spots of pSCNAs in normal tissues as well, suggesting that those regions might be inherently unstable. Prevalence of pSCNA in peripheral blood predicted survival, implying that mutations in normal tissues might have consequences for cancer patients.
authors.affiliation: Department of Medicine, University of Colorado School of Medicine, Aurora, CO 80045, USA.
authors.forename: Leila
authors.initials: L
authors.lastname: Aghili
authors.affiliation: School of Mathematics, University of Minnesota, Minneapolis, MN 55455, USA.
authors.forename: Jasmine
authors.initials: J
authors.lastname: Foo
authors.affiliation: Department of Biochemistry and Molecular Genetics, University of Colorado School of Medicine, Aurora, CO 80045, USA; Molecular Oncology Program, University of Colorado Cancer Center, Aurora, CO 80045, USA.
authors.forename: James
authors.initials: J
authors.lastname: DeGregori
authors.affiliation: Department of Medicine, University of Colorado School of Medicine, Aurora, CO 80045, USA; Molecular Oncology Program, University of Colorado Cancer Center, Aurora, CO 80045, USA; Department of Biostatistics and Informatics, Colorado School of Public Health, Aurora, CO 80045, USA. Electronic address: subhajyoti.de@ucdenver.edu.
authors.forename: Subhajyoti
authors.initials: S
authors.lastname: De
mesh_terms: D016022:Case-Control Studies; D056915:DNA Copy Number Variations; D005260:Female; D005784:Gene Amplification; D017353:Gene Deletion; D018628:Gene Dosage; D023281:Genomics / Q000379:methods; D006801:Humans; D008175:Lung Neoplasms / Q000235:genetics; D009154:Mutation; D010051:Ovarian Neoplasms / Q000097:blood / Q000235:genetics*; D017384:Sequence Deletion