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A BRCA2 mutation incorrectly mapped in the original BRCA2 reference sequence, is a common West Danish founder mutation disrupting mRNA splicing

Thomassen, Mads; Pedersen, Inge Sokilde; Vogel, Ida; Hansen, Thomas v. O.; Brasch-Andersen, Charlotte; Brasen, Claus L.; Cruger, Dorthe; Sunde, Lone; Nielsen, Finn C. and Jensen, Uffe B., et al. (2011) In Breast Cancer Research and Treatment 128(1). p.179-185
Abstract
Inherited mutations in the tumor suppressor genes BRCA1 and BRCA2 predispose carriers to breast and ovarian cancer. The authors have identified a mutation in BRCA2, 7845+1G > A (c.7617+1G > A), not previously regarded as deleterious because of incorrect mapping of the splice junction in the originally published genomic reference sequence. This reference sequence is generally used in many laboratories and it maps the mutation 16 base pairs inside intron 15. However, according to the recent reference sequences the mutation is located in the consensus donor splice sequence. By reverse transcriptase analysis, loss of exon 15 in the final transcript interrupting the open reading frame was demonstrated. Furthermore, the mutation segregates... (More)
Inherited mutations in the tumor suppressor genes BRCA1 and BRCA2 predispose carriers to breast and ovarian cancer. The authors have identified a mutation in BRCA2, 7845+1G > A (c.7617+1G > A), not previously regarded as deleterious because of incorrect mapping of the splice junction in the originally published genomic reference sequence. This reference sequence is generally used in many laboratories and it maps the mutation 16 base pairs inside intron 15. However, according to the recent reference sequences the mutation is located in the consensus donor splice sequence. By reverse transcriptase analysis, loss of exon 15 in the final transcript interrupting the open reading frame was demonstrated. Furthermore, the mutation segregates with a cancer phenotype in 18 Danish families. By genetic analysis of more than 3,500 Danish breast/ovarian cancer risk families, the mutation was identified as the most common BRCA2 mutation in West Denmark, while it is rare in Central and East Denmark and not identified in South Sweden. Haplotype analysis using dense SNP arrays indicated a common founder of the mutation approximately 1,500 years ago. (Less)
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keywords
Hereditary breast cancer, BRCA2, 7845+1G > A, Founder mutation, Mutation age, SNP array, RT-PCR
in
Breast Cancer Research and Treatment
volume
128
issue
1
pages
179 - 185
publisher
Springer
external identifiers
  • wos:000291656200020
  • scopus:79959275758
ISSN
1573-7217
DOI
10.1007/s10549-010-1272-6
project
CREATE Health
language
English
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yes
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81b520fa-fde6-40e1-9977-b09909f3e717 (old id 2056790)
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2011-08-02 09:00:30
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2017-01-01 06:22:32
@article{81b520fa-fde6-40e1-9977-b09909f3e717,
  abstract     = {Inherited mutations in the tumor suppressor genes BRCA1 and BRCA2 predispose carriers to breast and ovarian cancer. The authors have identified a mutation in BRCA2, 7845+1G > A (c.7617+1G > A), not previously regarded as deleterious because of incorrect mapping of the splice junction in the originally published genomic reference sequence. This reference sequence is generally used in many laboratories and it maps the mutation 16 base pairs inside intron 15. However, according to the recent reference sequences the mutation is located in the consensus donor splice sequence. By reverse transcriptase analysis, loss of exon 15 in the final transcript interrupting the open reading frame was demonstrated. Furthermore, the mutation segregates with a cancer phenotype in 18 Danish families. By genetic analysis of more than 3,500 Danish breast/ovarian cancer risk families, the mutation was identified as the most common BRCA2 mutation in West Denmark, while it is rare in Central and East Denmark and not identified in South Sweden. Haplotype analysis using dense SNP arrays indicated a common founder of the mutation approximately 1,500 years ago.},
  author       = {Thomassen, Mads and Pedersen, Inge Sokilde and Vogel, Ida and Hansen, Thomas v. O. and Brasch-Andersen, Charlotte and Brasen, Claus L. and Cruger, Dorthe and Sunde, Lone and Nielsen, Finn C. and Jensen, Uffe B. and Bisgaard, Marie Luise and Borg, Åke and Gerdes, Anne-Marie and Kruse, Torben A.},
  issn         = {1573-7217},
  keyword      = {Hereditary breast cancer,BRCA2,7845+1G > A,Founder mutation,Mutation age,SNP array,RT-PCR},
  language     = {eng},
  number       = {1},
  pages        = {179--185},
  publisher    = {Springer},
  series       = {Breast Cancer Research and Treatment},
  title        = {A BRCA2 mutation incorrectly mapped in the original BRCA2 reference sequence, is a common West Danish founder mutation disrupting mRNA splicing},
  url          = {http://dx.doi.org/10.1007/s10549-010-1272-6},
  volume       = {128},
  year         = {2011},
}