Large BRCA1 and BRCA2 genomic rearrangements in Danish high risk breast-ovarian cancer families
Research output: Contribution to journal › Journal article › Research › peer-review
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 language | English |
---|---|
Journal | Breast Cancer Research and Treatment |
Volume | 115 |
Issue number | 2 |
Pages (from-to) | 315-323 |
Number of pages | 9 |
ISSN | 0167-6806 |
DOIs | |
Publication status | Published - May 2009 |
- 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
Research areas
ID: 19796978