title: A systematic comparison of copy number alterations in four types of female cancer.
abstract: Detection and localization of genomic alterations and breakpoints are crucial in cancer research. The purpose of this study was to investigate, in a methodological and biological perspective, different female, hormone-dependent cancers to identify common and diverse DNA aberrations, genes, and pathways.
  
  
  
  In this work, we analyzed tissue samples from patients with breast (n = 112), ovarian (n = 74), endometrial (n = 84), or cervical (n = 76) cancer. To identify genomic aberrations, the Circular Binary Segmentation (CBS) and Piecewise Constant Fitting (PCF) algorithms were used and segmentation thresholds optimized. The Genomic Identification of Significant Targets in Cancer (GISTIC) algorithm was applied to the segmented data to identify significantly altered regions and the associated genes were analyzed by Ingenuity Pathway Analysis (IPA) to detect over-represented pathways and functions within the identified gene sets.
  
  
  
  Analyses of high-resolution copy number alterations in four different female cancer types are presented. For appropriately adjusted segmentation parameters the two segmentation algorithms CBS and PCF performed similarly. We identified one region at 8q24.3 with focal aberrations that was altered at significant frequency across all four cancer types. Considering both, broad regions and focal peaks, three additional regions with gains at significant frequency were revealed at 1p21.1, 8p22, and 13q21.33, respectively. Several of these events involve known cancer-related genes, like PPP2R2A, PSCA, PTP4A3, and PTK2. In the female reproductive system (ovarian, endometrial, and cervix [OEC]), we discovered three common events: copy number gains at 5p15.33 and 15q11.2, further a copy number loss at 8p21.2. Interestingly, as many as 75% of the aberrations (75% amplifications and 86% deletions) identified by GISTIC were specific for just one cancer type and represented distinct molecular pathways.
  
  
  
  Our results disclose that some prominent copy number changes are shared in the four examined female, hormone-dependent cancer whereas others are definitive to specific cancer types.
authors.affiliation: Department of Genetics, Institute for Cancer Research, Oslo University Hospital Radiumhospitalet, Oslo, Norway.|Medical Genetics Department, Oslo University Hospital Ullevål, Oslo, Norway.|Department of Pediatric Research, Division of Pediatric and Adolescent Medicine, Oslo University Hospital Rikshospitalet, Oslo, Norway.
authors.forename: Fatemeh
authors.initials: F
authors.lastname: Kaveh
authors.affiliation: Department of Genetics, Institute for Cancer Research, Oslo University Hospital Radiumhospitalet, Oslo, Norway.|Department of Pediatric Research, Division of Pediatric and Adolescent Medicine, Oslo University Hospital Rikshospitalet, Oslo, Norway.
authors.forename: Lars O
authors.initials: LO
authors.lastname: Baumbusch
authors.affiliation: Department of Genetics, Institute for Cancer Research, Oslo University Hospital Radiumhospitalet, Oslo, Norway.
authors.forename: Daniel
authors.initials: D
authors.lastname: Nebdal
authors.affiliation: Department of Genetics, Institute for Cancer Research, Oslo University Hospital Radiumhospitalet, Oslo, Norway.
authors.forename: Anne-Lise
authors.initials: AL
authors.lastname: Børresen-Dale
authors.affiliation: Department of Genetics, Institute for Cancer Research, Oslo University Hospital Radiumhospitalet, Oslo, Norway.|Department of Computer Science, University of Oslo, Oslo, Norway.
authors.forename: Ole Christian
authors.initials: OC
authors.lastname: Lingjærde
authors.affiliation: Department of Genetics, Institute for Cancer Research, Oslo University Hospital Radiumhospitalet, Oslo, Norway.
authors.forename: Hege
authors.initials: H
authors.lastname: Edvardsen
authors.affiliation: Department of Genetics, Institute for Cancer Research, Oslo University Hospital Radiumhospitalet, Oslo, Norway. v.n.kristensen@medisin.uio.no.|Department of Clinical Molecular Biology (EpiGen), Medical Division, Akershus University Hospital, Lørenskog, Norway. v.n.kristensen@medisin.uio.no.
authors.forename: Vessela N
authors.initials: VN
authors.lastname: Kristensen
authors.affiliation: Marine Mammals Research Group, Institute of Marine Research, Bergen, Norway.
authors.forename: Hiroko K
authors.initials: HK
authors.lastname: Solvang
mesh_terms: D001943:Breast Neoplasms / Q000235:genetics; D016000:Cluster Analysis; D056915:DNA Copy Number Variations; D030541:Databases, Genetic; D016889:Endometrial Neoplasms / Q000235:genetics; D005260:Female; D005784:Gene Amplification; D017353:Gene Deletion; D020869:Gene Expression Profiling; D056726:Genetic Association Studies; D020022:Genetic Predisposition to Disease; D023281:Genomics / Q000379:methods; D006801:Humans; D009369:Neoplasms / Q000175:diagnosis* / Q000235:genetics*; D010051:Ovarian Neoplasms / Q000235:genetics; D012737:Sex Factors; D002583:Uterine Cervical Neoplasms / Q000235:genetics
keywords: Breast cancer; Cervical cancer; Copy number alteration; Endometrial cancer; Female cancers; Genomic Identification of Significant Targets in Cancer; Ovarian cancer