title: Role of rare germline copy number variation in melanoma-prone patients.
abstract: OBJECTIVE
  This work evaluates a possible causative role for germline copy number variants (CNVs) in melanoma predisposition.
  
  
  METHODS
  A total of 41 melanoma-prone Brazilian patients were investigated for CNVs using 850K single nucleotide polymorphism arrays.
  
  
  RESULTS
  Ten rare CNVs were identified in nine patients, comprising 54 known genes, mostly related to cancer. In silico analyses revealed gene enrichment for cellular development and growth, and proliferation, highlighting five genes directly associated with the melanoma phenotype (ANGPT1, IDH1, PDE5A, HIST1H1B and GCNT2).
  
  
  CONCLUSIONS
  Patients harboring rare CNVs exhibited a decreased age of disease onset, in addition to an overall higher skin cancer predisposition. Our findings suggest that rare CNVs contribute to melanoma susceptibility, and should be taken into account when investigating cancer risk factors.
authors.affiliation: International Research Center, AC Camargo Cancer Center, São Paulo, Brazil.
authors.forename: Felipe
authors.initials: F
authors.lastname: Fidalgo
authors.affiliation: Department of Genetics & Evolutionary Biology, Institute of Biosciences, University of São Paulo, Brazil.
authors.forename: Tatiane Cristina
authors.initials: TC
authors.lastname: Rodrigues
authors.affiliation: Department of Genetics & Evolutionary Biology, Institute of Biosciences, University of São Paulo, Brazil.
authors.forename: Amanda Gonçalves
authors.initials: AG
authors.lastname: Silva
authors.affiliation: Department of Skin Cancer, AC Camargo Cancer Center, São Paulo, Brazil.
authors.forename: Luciana
authors.initials: L
authors.lastname: Facure
authors.affiliation: Department of Skin Cancer, AC Camargo Cancer Center, São Paulo, Brazil.
authors.forename: Bianca Costa Soares
authors.initials: BC
authors.lastname: de Sá
authors.affiliation: Department of Skin Cancer, AC Camargo Cancer Center, São Paulo, Brazil.
authors.forename: João Pedreira
authors.initials: JP
authors.lastname: Duprat
authors.affiliation: Department of Oncogenetics, AC Camargo Cancer Center, São Paulo, Brazil.
authors.forename: Maria Isabel
authors.initials: MI
authors.lastname: Achatz
authors.affiliation: Department of Genetics & Evolutionary Biology, Institute of Biosciences, University of São Paulo, Brazil.
authors.forename: Carla
authors.initials: C
authors.lastname: Rosenberg
authors.affiliation: International Research Center, AC Camargo Cancer Center, São Paulo, Brazil.
authors.forename: Dirce Maria
authors.initials: DM
authors.lastname: Carraro
authors.affiliation: Department of Genetics & Evolutionary Biology, Institute of Biosciences, University of São Paulo, Brazil.
authors.forename: Ana Cristina Victorino
authors.initials: AC
authors.lastname: Krepischi
mesh_terms: D000328:Adult; D056915:DNA Copy Number Variations / Q000235:genetics*; D005260:Female; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D018095:Germ-Line Mutation; D006801:Humans; D008297:Male; D008545:Melanoma / Q000235:genetics*; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D060888:Real-Time Polymerase Chain Reaction; D012189:Retrospective Studies; D012878:Skin Neoplasms / Q000235:genetics*
keywords: ANGPT1; CNV; GCNT2; HIST1H1B; IDH1; PDE5A; cancer predisposition; copy number variation; familial melanoma; germline; histone cluster; melanoma-prone; sporadic multiple primary melanomas