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

Thomas v O Hansen; Lars Jønson; Anders Albrechtsen; Mette K Andersen; Bent Ejlertsen; Finn C Nielsen

doi:10.1007/s10549-008-0088-0

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

Thomas v O Hansen, Lars Jønson, Anders Albrechtsen, Mette K Andersen, Bent Ejlertsen, Finn C Nielsen

Computational and RNA Biology

46 Citations (Scopus)

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 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	https://doi.org/10.1007/s10549-008-0088-0
Publication status	Published - 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

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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title = "Large BRCA1 and BRCA2 genomic rearrangements in Danish high risk breast-ovarian cancer families",

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.",

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",

author = "Hansen, {Thomas v O} and Lars J{\o}nson and Anders Albrechtsen and Andersen, {Mette K} and Bent Ejlertsen and Nielsen, {Finn C}",

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doi = "10.1007/s10549-008-0088-0",

language = "English",

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pages = "315--323",

journal = "Breast Cancer Research and Treatment",

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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 -

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

Abstract

Keywords

UN SDGs

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