Breast Cancer Research and Treatment

, Volume 119, Issue 3, pp 547–550 | Cite as

The silent mutation nucleotide 744 G → A, Lys172Lys, in exon 6 of BRCA2 results in exon skipping

  • Thomas V. O. HansenEmail author
  • Ane Y. Steffensen
  • Lars Jønson
  • Mette K. Andersen
  • Bent Ejlertsen
  • Finn C. Nielsen
Preclinical Study


Germ-line mutations in BRCA2 predispose to breast and ovarian cancer. Mutations are widespread throughout the gene and include disease-causing mutations as frameshift, nonsense, splicing mutations and large genomic rearrangements. However a large number of mutations, including missense, silent and intron variants are of unknown significance. Here, we describe the functional characterization of a silent mutation (nucleotide 744 G → A/c.516 G → A, Lys172Lys) in exon 6 of BRCA2 in a Danish family with breast and ovarian cancer. Exon trapping analysis showed that the mutation results in skipping of exon 6 and/or both exon 5 and 6, which was verified by RT-PCR analysis on RNA isolated from whole blood of the affected patient. We therefore conclude that the BRCA2 silent mutation Lys172Lys is a disease-causing mutation.


Breast cancer BRCA2 Silent mutation Splicing Exon trapping RT-PCR 



This study was supported by the Neye Foundation and the Danish Cancer Society.


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Copyright information

© Springer Science+Business Media, LLC. 2009

Authors and Affiliations

  • Thomas V. O. Hansen
    • 1
    Email author
  • Ane Y. Steffensen
    • 1
  • Lars Jønson
    • 1
  • Mette K. Andersen
    • 2
  • Bent Ejlertsen
    • 3
  • Finn C. Nielsen
    • 1
  1. 1.Department of Clinical Biochemistry 4111RigshospitaletCopenhagenDenmark
  2. 2.Department of Clinical Genetics, The Juliane Marie CenterRigshospitaletCopenhagenDenmark
  3. 3.Department of OncologyRigshospitaletCopenhagenDenmark

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