Affiliations: Center for Medical Genetics and Molecular Medicine,
Haukeland University Hospital, N-5021 Bergen, Norway | Present address: Section of Genetic Counseling,
Department of Cancer Genetics, The Norwegian Radium Hospital, N-0310, Oslo,
Norway | Present address: Institute of Marine Research, P.O.
Box. 1870 Nordnes, N-5817 Bergen, 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.
Keywords: familial cancer, breast cancer only, BRCA1, 5'UTR, genetic screening, haplotypes
