title: Mutation analysis of the BCCIP gene for breast cancer susceptibility in breast/ovarian cancer families.
abstract: OBJECTIVE
  About 5%-10% of breast cancer is due to inherited disease predisposition. Currently, mutations in the BRCA1 and BRCA2 genes explain less than 25% of the familial clustering of breast cancer, and additional susceptibility genes are suspected. The BCCIP gene plays an important role in the regulation of gene transcription and cell proliferation and could be involved in the maintenance of genomic integrity. The BCCIP protein binds in mammalian cells to the longest conserved region of the BRCA2 protein and is required for BRCA2 stability and function, making a critical contribution to the function of BRCA2 in mediating homologous recombination. Variants in the BCCIP gene could affect the BRCA2 functionality and be associated to the familial breast/ovarian carcinogenesis. Therefore, BCCIP gene is a potential candidate for being involved in heritable cancer susceptibility.
  
  
  METHODS
  We have screened the entire coding region and splice junctions of BCCIP in affected index cases from 215 Spanish breast/ovarian cancer families for germ line defects, using direct sequencing.
  
  
  RESULTS
  Mutation analysis revealed 3 different intronic sequence changes.
  
  
  CONCLUSIONS
  Based on the in silico and in vitro RNA analyses of these sequence alterations, none of them were predicted to be pathogenic or associated with cancer susceptibility. Our results indicate that BCCIP germ line mutations are unlikely to be a major contributor to familial breast/ovarian cancer risk in our population.
authors.affiliation: Oncogenetics Laboratory, Vall d'Hebron Institute of Oncology (VHIO), Universitat Autonoma de Barcelona, Barcelona, Spain; Oncogenetics Laboratory, Vall d'Hebron Research Institute (VHIR), Universitat Autonoma de Barcelona, Barcelona, Spain. Electronic address: sbonache@vhebron.net.
authors.forename: Sandra
authors.initials: S
authors.lastname: Bonache
authors.forename: Sara
authors.initials: S
authors.lastname: Gutierrez-Enriquez
authors.forename: Anna
authors.initials: A
authors.lastname: Tenés
authors.forename: Miriam
authors.initials: M
authors.lastname: Masas
authors.forename: Judith
authors.initials: J
authors.lastname: Balmaña
authors.forename: Orland
authors.initials: O
authors.lastname: Diez
mesh_terms: D019313:BRCA1 Protein / Q000172:deficiency; D024682:BRCA2 Protein / Q000172:deficiency; D001943:Breast Neoplasms / Q000235:genetics*; D018567:Breast Neoplasms, Male / Q000235:genetics; D002135:Calcium-Binding Proteins / Q000235:genetics*; D018797:Cell Cycle Proteins / Q000235:genetics*; D004252:DNA Mutational Analysis; D005091:Exons; D005192:Family Health; D005260:Female; D020022:Genetic Predisposition to Disease; D018095:Germ-Line Mutation; D006801:Humans; D007438:Introns; D008297:Male; D009687:Nuclear Proteins / Q000235:genetics*; D010051:Ovarian Neoplasms / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide
chemical_list: C415366:BCCIP protein, human; D019313:BRCA1 Protein; C492913:BRCA1 protein, human; D024682:BRCA2 Protein; C551750:BRCA2 protein, human; D002135:Calcium-Binding Proteins; D018797:Cell Cycle Proteins; D009687:Nuclear Proteins
keywords: BCCIP; Familial breast/ovarian cancer; Mutational analysis