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

Mads Thomassen; Inge Søkilde Pedersen; Ida Vogel; Thomas V O Hansen; Charlotte Brasch-Andersen; Claus L Brasen; Dorthe Crüger; Lone E. M. Sunde; Finn C Nielsen; Uffe Birk Jensen; Marie Luise Bisgaard; Ake Borg; Anne-Marie Gerdes; Torben A Kruse

doi:10.1007/s10549-010-1272-6

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

Mads Thomassen, Inge Søkilde Pedersen, Ida Vogel, Thomas V O Hansen, Charlotte Brasch-Andersen, Claus L Brasen, Dorthe Crüger, Lone E. M. Sunde, Finn C Nielsen, Uffe Birk Jensen, Marie Luise Bisgaard, Ake Borg, Anne-Marie Gerdes, Torben A Kruse

Department of Cellular and Molecular Medicine

4 Citations (Scopus)

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.

Original language	English
Journal	Breast Cancer Research and Treatment
Volume	128
Issue number	1
Pages (from-to)	179-85
Number of pages	7
ISSN	0167-6806
DOIs	https://doi.org/10.1007/s10549-010-1272-6
Publication status	Published - 1 Jul 2011

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Thomassen, M., Pedersen, I. S., Vogel, I., Hansen, T. V. O., Brasch-Andersen, C., Brasen, C. L., Crüger, D., Sunde, L. E. M., Nielsen, F. C., Jensen, U. B., Bisgaard, M. L., Borg, A., Gerdes, A-M., & Kruse, T. A. (2011). A BRCA2 mutation incorrectly mapped in the original BRCA2 reference sequence, is a common West Danish founder mutation disrupting mRNA splicing. Breast Cancer Research and Treatment, 128(1), 179-85. https://doi.org/10.1007/s10549-010-1272-6

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 Søkilde; Vogel, Ida et al.

In: Breast Cancer Research and Treatment, Vol. 128, No. 1, 01.07.2011, p. 179-85.

Research output: Contribution to journal › Journal article › Research › peer-review

Thomassen, M, Pedersen, IS, Vogel, I, Hansen, TVO, Brasch-Andersen, C, Brasen, CL, Crüger, D, Sunde, LEM, Nielsen, FC, Jensen, UB, Bisgaard, ML, Borg, A, Gerdes, A-M & Kruse, TA 2011, 'A BRCA2 mutation incorrectly mapped in the original BRCA2 reference sequence, is a common West Danish founder mutation disrupting mRNA splicing', Breast Cancer Research and Treatment, vol. 128, no. 1, pp. 179-85. https://doi.org/10.1007/s10549-010-1272-6

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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.",

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AU - Thomassen, Mads

AU - Pedersen, Inge Søkilde

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AU - Hansen, Thomas V O

AU - Brasch-Andersen, Charlotte

AU - Brasen, Claus L

AU - Crüger, Dorthe

AU - Sunde, Lone E. M.

AU - Nielsen, Finn C

AU - Jensen, Uffe Birk

AU - Bisgaard, Marie Luise

AU - Borg, Ake

AU - Gerdes, Anne-Marie

AU - Kruse, Torben A

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N2 - 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.

AB - 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.

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DO - 10.1007/s10549-010-1272-6

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JO - Breast Cancer Research and Treatment

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IS - 1

ER -

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

Abstract

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