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

TY - JOUR

T1 - Large BRCA1 and BRCA2 genomic rearrangements in Danish high risk breast-ovarian cancer families

AU - Hansen, Thomas v O

AU - Jønson, Lars

AU - Albrechtsen, Anders

AU - Andersen, Mette K

AU - Ejlertsen, Bent

AU - Nielsen, Finn C

PY - 2009/5

Y1 - 2009/5

N2 - 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.

AB - 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.

KW - Base Sequence

KW - Breast Neoplasms

KW - Denmark

KW - Female

KW - Founder Effect

KW - Gene Rearrangement

KW - Genes, BRCA1

KW - Genes, BRCA2

KW - Genetic Predisposition to Disease

KW - Humans

KW - Male

KW - Molecular Sequence Data

KW - Mutation

KW - Oligonucleotide Array Sequence Analysis

KW - Ovarian Neoplasms

KW - Pedigree

KW - Polymerase Chain Reaction

KW - Polymorphism, Single Nucleotide

KW - Risk Factors

U2 - 10.1007/s10549-008-0088-0

DO - 10.1007/s10549-008-0088-0

M3 - Journal article

C2 - 18546071

SN - 0167-6806

VL - 115

SP - 315

EP - 323

JO - Breast Cancer Research and Treatment

JF - Breast Cancer Research and Treatment

IS - 2

ER -