title: Analysis of SLX4/FANCP in non-BRCA1/2-mutated breast cancer families.
abstract: BACKGROUND
  Genes that, when mutated, cause Fanconi anemia or greatly increase breast cancer risk encode for proteins that converge on a homology-directed DNA damage repair process. Mutations in the SLX4 gene, which encodes for a scaffold protein involved in the repair of interstrand cross-links, have recently been identified in unclassified Fanconi anemia patients. A mutation analysis of SLX4 in German or Byelorussian familial cases of breast cancer without detected mutations in BRCA1 or BRCA2 has been completed, with globally negative results.
  
  
  METHODS
  The genomic region of SLX4, comprising all exons and exon-intron boundaries, was sequenced in 94 Spanish familial breast cancer cases that match a criterion indicating the potential presence of a highly-penetrant germline mutation, following exclusion of BRCA1 or BRCA2 mutations.
  
  
  RESULTS
  This mutational analysis revealed extensive genetic variation of SLX4, with 21 novel single nucleotide variants; however, none could be linked to a clear alteration of the protein function. Nonetheless, genotyping 10 variants (nine novel, all missense amino acid changes) in a set of controls (138 women and 146 men) did not detect seven of them.
  
  
  CONCLUSIONS
  Overall, while the results of this study do not identify clearly pathogenic mutations of SLX4 contributing to breast cancer risk, further genetic analysis, combined with functional assays of the identified rare variants, may be warranted to conclusively assess the potential link with the disease.
authors.affiliation: Hereditary Cancer Program, Catalan Institute of Oncology (ICO), Hospital Duran i Reynals, Bellvitge Institute for Biomedical Research (IDIBELL), L'Hospitalet, Barcelona, Catalonia, Spain.
authors.forename: Juana
authors.initials: J
authors.lastname: Fernández-Rodríguez
authors.forename: Francisco
authors.initials: F
authors.lastname: Quiles
authors.forename: Ignacio
authors.initials: I
authors.lastname: Blanco
authors.forename: Alex
authors.initials: A
authors.lastname: Teulé
authors.forename: Lídia
authors.initials: L
authors.lastname: Feliubadaló
authors.forename: Jesús Del
authors.initials: JD
authors.lastname: Valle
authors.forename: Mónica
authors.initials: M
authors.lastname: Salinas
authors.forename: Angel
authors.initials: A
authors.lastname: Izquierdo
authors.forename: Esther
authors.initials: E
authors.lastname: Darder
authors.forename: Detlev
authors.initials: D
authors.lastname: Schindler
authors.forename: Gabriel
authors.initials: G
authors.lastname: Capellá
authors.forename: Joan
authors.initials: J
authors.lastname: Brunet
authors.forename: Conxi
authors.initials: C
authors.lastname: Lázaro
authors.forename: Miguel Angel
authors.initials: MA
authors.lastname: Pujana
mesh_terms: D001943:Breast Neoplasms / Q000235:genetics*; D004252:DNA Mutational Analysis; D005091:Exons / Q000235:genetics; D005190:Family; D005260:Female; D019398:Genes, BRCA1; D024522:Genes, BRCA2; D020022:Genetic Predisposition to Disease; D018095:Germ-Line Mutation / Q000235:genetics; D006801:Humans; D007438:Introns / Q000235:genetics; D008297:Male; D020125:Mutation, Missense / Q000235:genetics*; D045522:Recombinases / Q000235:genetics*
chemical_list: D045522:Recombinases; C542319:SLX4 protein, human