Large BRCA1 and BRCA2 genomic rearrangements in Danish high risk breast-ovarian cancer families

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Abstract

BRCA1 and BRCA2 germ-line mutations predispose to breast and ovarian cancer. Large genomic rearrangements of BRCA1 account for 0-36% of all disease causing mutations in various populations, while large genomic rearrangements in BRCA2 are more rare. We examined 642 East Danish breast and/or ovarian cancer patients in whom a deleterious mutation in BRCA1 and BRCA2 was not detected by sequencing using the multiplex ligation-dependent probe amplification (MLPA) assay. We identified 15 patients with 7 different genomic rearrangements, including a BRCA1 exon 5-7 deletion with a novel breakpoint, a BRCA1 exon 13 duplication, a BRCA1 exon 17-19 deletion, a BRCA1 exon 3-16 deletion, and a BRCA2 exon 20 deletion with a novel breakpoint as well as two novel BRCA1 exon 17-18 and BRCA1 exon 19 deletions. The large rearrangements in BRCA1 and BRCA2 accounted for 9.2% (15/163) of all BRCA1 and BRCA2 mutations in East Denmark. Nine patients had the exon 3-16 deletion in BRCA1. By SNP analysis we find that the patients share a 5 Mb fragment of chromosome 17, including BRCA1, indicating that the exon 3-16 deletion represents a Danish founder mutation.
Original languageEnglish
JournalBreast Cancer Research and Treatment
Volume115
Issue number2
Pages (from-to)315-323
Number of pages9
ISSN0167-6806
DOIs
Publication statusPublished - May 2009

Keywords

  • Base Sequence
  • Breast Neoplasms
  • Denmark
  • Female
  • Founder Effect
  • Gene Rearrangement
  • Genes, BRCA1
  • Genes, BRCA2
  • Genetic Predisposition to Disease
  • Humans
  • Male
  • Molecular Sequence Data
  • Mutation
  • Oligonucleotide Array Sequence Analysis
  • Ovarian Neoplasms
  • Pedigree
  • Polymerase Chain Reaction
  • Polymorphism, Single Nucleotide
  • Risk Factors

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