title: EMSY copy number variation in male breast cancers characterized for BRCA1 and BRCA2 mutations.
abstract: Male breast cancer (MBC) is a rare disease that shares some similarities with female breast cancer (FBC). Like FBC, genetic susceptibility to MBC can be referred to mutations in BRCA1 and, particularly, BRCA2 genes. However, only about 10 % of MBCs are caused by BRCA1/2 germ-line mutations, while the largest part are sporadic cancers and may derive from somatic alterations. EMSY, a BRCA2 inactivating gene, emerged as a candidate gene involved in the pathogenesis of sporadic FBC, and its amplification was suggested to be the somatic counterpart of BRCA2 mutations. Considering the relevant role of BRCA2 in MBC, we aimed at investigating the role of EMSY gene copy number variations in male breast tumors.
  
  
  
  EMSY copy number variations were analyzed by quantitative real-time PCR with TaqMan probes in a selected series of 75 MBCs, characterized for BRCA1/2 mutations.
  
  
  
  We reported EMSY amplification in 34.7 % of MBCs. A significant association emerged between EMSY amplification and BRCA1/2 mutations (p = 0.03). We identified two amplification subgroups characterized by low and high amplification levels, with BRCA2-related tumors mostly showing low EMSY amplification.
  
  
  
  Our results show a high frequency of EMSY amplification in MBC, thus pointing to a role of EMSY in the pathogenesis of this disease. EMSY amplification may be a new feature that might uncover underlying molecular pathways of MBCs and may allow for the identification of MBC subgroups with potential clinical implication for targeted therapeutic approaches.
authors.affiliation: Department of Molecular Medicine, Sapienza University of Rome, Viale Regina Elena 324, 00161, Rome, Italy.
authors.forename: Anna Sara
authors.initials: AS
authors.lastname: Navazio
authors.affiliation: Department of Molecular Medicine, Sapienza University of Rome, Viale Regina Elena 324, 00161, Rome, Italy.
authors.forename: Piera
authors.initials: P
authors.lastname: Rizzolo
authors.affiliation: Department of Molecular Medicine, Sapienza University of Rome, Viale Regina Elena 324, 00161, Rome, Italy.
authors.forename: Valentina
authors.initials: V
authors.lastname: Silvestri
authors.affiliation: Department of Molecular Medicine, Sapienza University of Rome, Viale Regina Elena 324, 00161, Rome, Italy.
authors.forename: Virginia
authors.initials: V
authors.lastname: Valentini
authors.affiliation: Department of Molecular Medicine, Sapienza University of Rome, Viale Regina Elena 324, 00161, Rome, Italy.
authors.forename: Veronica
authors.initials: V
authors.lastname: Zelli
authors.affiliation: Molecular and Nutritional Epidemiology Unit, Cancer Research and Prevention Institute (ISPO), Florence, Italy.
authors.forename: Ines
authors.initials: I
authors.lastname: Zanna
authors.affiliation: Molecular and Nutritional Epidemiology Unit, Cancer Research and Prevention Institute (ISPO), Florence, Italy.
authors.forename: Giovanna
authors.initials: G
authors.lastname: Masala
authors.affiliation: Division of Pathological Anatomy, Department of Medical and Surgical Critical Care, University of Florence, Florence, Italy.
authors.forename: Simonetta
authors.initials: S
authors.lastname: Bianchi
authors.affiliation: Molecular Genetics Laboratory, Istituto Tumori "Giovanni Paolo II", Bari, Italy.
authors.forename: Stefania
authors.initials: S
authors.lastname: Tommasi
authors.affiliation: Molecular and Nutritional Epidemiology Unit, Cancer Research and Prevention Institute (ISPO), Florence, Italy.
authors.forename: Domenico
authors.initials: D
authors.lastname: Palli
authors.affiliation: Department of Molecular Medicine, Sapienza University of Rome, Viale Regina Elena 324, 00161, Rome, Italy. laura.ottini@uniroma1.it.
authors.forename: Laura
authors.initials: L
authors.lastname: Ottini
mesh_terms: D014408:Biomarkers, Tumor; D018567:Breast Neoplasms, Male / Q000175:diagnosis / Q000235:genetics*; D056915:DNA Copy Number Variations; D005784:Gene Amplification; D019398:Genes, BRCA1; D024522:Genes, BRCA2; D020022:Genetic Predisposition to Disease; D005820:Genetic Testing / Q000379:methods; D018095:Germ-Line Mutation; D006801:Humans; D008297:Male; D009154:Mutation; D060787:Neoplasm Grading; D009363:Neoplasm Proteins / Q000235:genetics*; D009367:Neoplasm Staging; D009687:Nuclear Proteins / Q000235:genetics*; D012097:Repressor Proteins / Q000235:genetics*
chemical_list: D014408:Biomarkers, Tumor; C480344:EMSY protein, human; D009363:Neoplasm Proteins; D009687:Nuclear Proteins; D012097:Repressor Proteins
keywords: BRCA1/2 germ-line mutations; Copy number variation; EMSY; Male breast cancer