title: Complete mutation screening and haplotype characterization of the BRCA1 gene in 61 familial breast cancer patients from Norway.
abstract: Mutations in the Breast-Cancer-1 (BRCA1) gene are the major cause of familial breast/ovarian cancer. Among familial breast cancer only, 15-20% have been suggested to have a deleterious mutation in BRCA1. A highly sensitive method (REF-SSCP) was applied to screen the open reading frame and the 5'UTRs of BRCA1 for mutations. The patient cohort comprised 61 unrelated moderate to high risk breast cancer patients from Western-Norway. Only one known deleterious BRCA1 mutation (c.816-817delGT) was found in two of the 61 patients (3.3%). Four haplotypes were established based on nine known single nucleotide polymorphisms. Two patients had a novel deletion (c.-33_-29delAAAAA) in the 5'UTR, and a novel amino acid substitution (L523W) was found in one patient. Size variations analysis in the 5'UTR was repeated in a cohort of 159 unrelated familial breast/ovarian cancer patients and 94 healthy blood donors. Two patients were identified with 5'UTR (c.-30 to -60) variations (CAAAA)5 and (CAAAA)7, instead of the (CAAAA)6-repeat. All of the identified 5'UTR size variations were localized between the start codon and the most stable secondary structures previously proposed for the exon 1b transcript. No such alterations were found among the healthy blood donors but association studies of the 5'UTR variations within the respective families were not conclusive.
authors.affiliation: Center for Medical Genetics and Molecular Medicine, Haukeland University Hospital, N-5021 Bergen, Norway. petter.frost@imr.no
authors.forename: Petter
authors.initials: P
authors.lastname: Frost
authors.forename: Astanand
authors.initials: A
authors.lastname: Jugessur
authors.forename: Jaran
authors.initials: J
authors.lastname: Apold
authors.forename: Ketil
authors.initials: K
authors.lastname: Heimdal
authors.forename: Thomas
authors.initials: T
authors.lastname: Aloysius
authors.forename: Aud K
authors.initials: AK
authors.lastname: Eliassen
authors.forename: Lars
authors.initials: L
authors.lastname: Fauske
authors.forename: Guri
authors.initials: G
authors.lastname: Matre
authors.forename: Hans Geir
authors.initials: HG
authors.lastname: Eiken
mesh_terms: D020121:5' Untranslated Regions / Q000235:genetics; D000328:Adult; D019313:BRCA1 Protein / Q000235:genetics*; D001943:Breast Neoplasms / Q000235:genetics*; D005260:Female; D018703:Founder Effect; D019398:Genes, BRCA1; D005820:Genetic Testing; D006239:Haplotypes; D006801:Humans; D008875:Middle Aged; D009154:Mutation; D009664:Norway; D012150:Polymorphism, Restriction Fragment Length; D018807:Polymorphism, Single-Stranded Conformational
chemical_list: D020121:5' Untranslated Regions; D019313:BRCA1 Protein