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Åke Borg

Åke Borg

Principal investigator

Åke Borg

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

Author

  • Mads Thomassen
  • Inge Sokilde Pedersen
  • Ida Vogel
  • Thomas v. O. Hansen
  • Charlotte Brasch-Andersen
  • Claus L. Brasen
  • Dorthe Cruger
  • Lone Sunde
  • Finn C. Nielsen
  • Uffe B. Jensen
  • Marie Luise Bisgaard
  • Åke Borg
  • Anne-Marie Gerdes
  • Torben A. Kruse
Show all

Summary, in English

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.

Department/s

  • Breastcancer-genetics
  • BioCARE: Biomarkers in Cancer Medicine improving Health Care, Education and Innovation

Publishing year

2011

Language

English

Pages

179-185

Publication/Series

Breast Cancer Research and Treatment

Volume

128

Issue

1

Document type

Journal article

Publisher

Springer

Topic

  • Cancer and Oncology

Keywords

  • Hereditary breast cancer
  • BRCA2
  • 7845+1G > A
  • Founder mutation
  • Mutation age
  • SNP array
  • RT-PCR

Status

Published

ISBN/ISSN/Other

  • ISSN: 1573-7217