title: Low prevalence of SLX4 loss-of-function mutations in non-BRCA1/2 breast and/or ovarian cancer families.
abstract: Fanconi anemia is a genetically heterogeneous autosomal recessive disorder characterized by development abnormalities, bone marrow failure, and childhood cancers. Compelling evidence indicates a common genetic basis for FA and breast/ovarian cancer susceptibility. Recently, biallelic germ-line mutations in SLX4 have been demonstrated to cause a previously unknown FA subtype (FA-P). We address the role of SLX4/FANCP in breast/ovarian cancer susceptibility by conducting a comprehensive mutation scanning in 486 index cases from non-BRCA1/BRCA2 multiple-case breast and/or ovarian cancer families (non-BRCA1/2 families) from Spain. We detected one unequivocal loss-of-function mutation (p.Glu1517X). In addition, one missense change (p.Arg372Trp) predicted to be pathogenic by in silico analysis co-segregates with disease in one family. Overall, the study indicates that SLX4 mutation screening will have a very low impact (if any) in the genetic counseling of non-BRCA1/2 families.
authors.affiliation: Laboratorio de Oncología Molecular, Instituto de Investigación Sanitaria San Carlos, Madrid, Spain.
authors.forename: Gorka Ruiz
authors.initials: GR
authors.lastname: de Garibay
authors.forename: Avellaneda
authors.initials: A
authors.lastname: Díaz
authors.forename: Belén
authors.initials: B
authors.lastname: Gaviña
authors.forename: Atocha
authors.initials: A
authors.lastname: Romero
authors.forename: Pilar
authors.initials: P
authors.lastname: Garre
authors.forename: Ana
authors.initials: A
authors.lastname: Vega
authors.forename: Ana
authors.initials: A
authors.lastname: Blanco
authors.forename: Alicia
authors.initials: A
authors.lastname: Tosar
authors.forename: Orland
authors.initials: O
authors.lastname: Díez
authors.forename: Pedro
authors.initials: P
authors.lastname: Pérez-Segura
authors.forename: Eduardo
authors.initials: E
authors.lastname: Díaz-Rubio
authors.forename: Trinidad
authors.initials: T
authors.lastname: Caldés
authors.forename: Miguel
authors.initials: M
authors.lastname: de la Hoya
mesh_terms: D019313:BRCA1 Protein / Q000235:genetics; D024682:BRCA2 Protein / Q000235:genetics; D001943:Breast Neoplasms / Q000235:genetics*; D004252:DNA Mutational Analysis; D005192:Family Health; D005199:Fanconi Anemia / Q000235:genetics; D005260:Female; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease / Q000235:genetics; D018095:Germ-Line Mutation; D006801:Humans; D008297:Male; D010051:Ovarian Neoplasms / Q000235:genetics*; D010375:Pedigree; D045522:Recombinases / Q000235:genetics*
chemical_list: D019313:BRCA1 Protein; D024682:BRCA2 Protein; C551750:BRCA2 protein, human; D045522:Recombinases; C542319:SLX4 protein, human