Large BRCA1 and BRCA2 genomic rearrangements in Danish high risk breast-ovarian cancer families
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Large BRCA1 and BRCA2 genomic rearrangements in Danish high risk breast-ovarian cancer families. / Hansen, Thomas v O; Jønson, Lars; Albrechtsen, Anders; Andersen, Mette K; Ejlertsen, Bent; Nielsen, Finn C.
In: Breast Cancer Research and Treatment, Vol. 115, No. 2, 05.2009, p. 315-323.Research output: Contribution to journal › Journal article › Research › peer-review
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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
VL - 115
SP - 315
EP - 323
JO - Breast Cancer Research and Treatment
JF - Breast Cancer Research and Treatment
SN - 0167-6806
IS - 2
ER -
ID: 19796978