title: DNA copy number profiling reveals extensive genomic loss in hereditary BRCA1 and BRCA2 ovarian carcinomas.
abstract: BACKGROUND
  Few studies have attempted to characterise genomic changes occurring in hereditary epithelial ovarian carcinomas (EOCs) and inconsistent results have been obtained. Given the relevance of DNA copy number alterations in ovarian oncogenesis and growing clinical implications of the BRCA-gene status, we aimed to characterise the genomic profiles of hereditary and sporadic ovarian tumours.
  
  
  METHODS
  High-resolution array Comparative Genomic Hybridisation profiling of 53 familial (21 BRCA1, 6 BRCA2 and 26 non-BRCA1/2) and 15 sporadic tumours in combination with supervised and unsupervised analysis was used to define common and/or specific copy number features.
  
  
  RESULTS
  Unsupervised hierarchical clustering did not stratify tumours according to their familial or sporadic condition or to their BRCA1/2 mutation status. Common recurrent changes, spanning genes potentially fundamental for ovarian carcinogenesis, regardless of BRCA mutations, and several candidate subtype-specific events were defined. Despite similarities, greater contribution of losses was revealed to be a hallmark of BRCA1 and BRCA2 tumours.
  
  
  CONCLUSIONS
  Somatic alterations occurring in the development of familial EOCs do not differ substantially from the ones occurring in sporadic carcinomas. However, some specific features like extensive genomic loss observed in BRCA1/2 tumours may be of clinical relevance helping to identify BRCA-related patients likely to respond to PARP inhibitors.
authors.affiliation: Human Cancer Genetics, Spanish National Cancer Research Center (CNIO), C/Melchor Fernández Almagro 3, 28029 Madrid, Spain.
authors.forename: M M
authors.initials: MM
authors.lastname: Kamieniak
authors.forename: I
authors.initials: I
authors.lastname: Muñoz-Repeto
authors.forename: D
authors.initials: D
authors.lastname: Rico
authors.forename: A
authors.initials: A
authors.lastname: Osorio
authors.forename: M
authors.initials: M
authors.lastname: Urioste
authors.forename: J
authors.initials: J
authors.lastname: García-Donas
authors.forename: S
authors.initials: S
authors.lastname: Hernando
authors.forename: L
authors.initials: L
authors.lastname: Robles-Díaz
authors.forename: T
authors.initials: T
authors.lastname: Ramón Y Cajal
authors.forename: A
authors.initials: A
authors.lastname: Cazorla
authors.forename: R
authors.initials: R
authors.lastname: Sáez
authors.forename: J M
authors.initials: JM
authors.lastname: García-Bueno
authors.forename: S
authors.initials: S
authors.lastname: Domingo
authors.forename: S
authors.initials: S
authors.lastname: Borrego
authors.forename: J
authors.initials: J
authors.lastname: Palacios
authors.forename: M A
authors.initials: MA
authors.lastname: van de Wiel
authors.forename: B
authors.initials: B
authors.lastname: Ylstra
authors.forename: J
authors.initials: J
authors.lastname: Benítez
authors.forename: M J
authors.initials: MJ
authors.lastname: García
mesh_terms: D000077216:Carcinoma, Ovarian Epithelial; D055028:Comparative Genomic Hybridization; D056915:DNA Copy Number Variations; D004273:DNA, Neoplasm / Q000235:genetics / Q000302:isolation & purification; D005260:Female; D005557:Formaldehyde; D019398:Genes, BRCA1; D024522:Genes, BRCA2; D042822:Genomic Instability; D018095:Germ-Line Mutation; D006801:Humans; D007150:Immunohistochemistry; D009375:Neoplasms, Glandular and Epithelial / Q000235:genetics*; D010051:Ovarian Neoplasms / Q000235:genetics*; D016612:Paraffin Embedding; D016707:Tissue Fixation
chemical_list: D004273:DNA, Neoplasm; D005557:Formaldehyde
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