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Breast Cancer Research and Treatment

, Volume 115, Issue 1, pp 69–76 | Cite as

A common Greenlandic Inuit BRCA1 RING domain founder mutation

  • Thomas v. O. HansenEmail author
  • Bent Ejlertsen
  • Anders Albrechtsen
  • Eva Bergsten
  • Peter Bjerregaard
  • Torben Hansen
  • Torben Myrhøj
  • Peter B. Nielsen
  • Vera Timmermans-Wielenga
  • Mette K. Andersen
  • Lars Jønson
  • Finn C. Nielsen
Preclinical Study

Abstract

Germ-line mutations in the tumour suppressor proteins BRCA1 and BRCA2 predispose to breast and ovarian cancer. We examined 32 breast and/or ovarian cancer patients from Greenland for mutations in BRCA1 and BRCA2. Whereas no mutations were identified in 19 families, 13 families exhibited a BRCA1 exon 3 nucleotide 234 T > G mutation, which has not previously been reported in the breast cancer information core (BIC) database. The mutation changes a conserved cysteine 39 to a glycine in the Zn2+ site II of the RING domain, which is essential for BRCA1 ubiquitin ligase activity. Eight of the families had members with ovarian cancer, suggesting that the RING domain may be an ovarian cancer hotspot. By SNP array analysis, we find that all 13 families share a 4.5 Mb genomic fragment containing the BRCA1 gene, showing that the mutation originates from a founder. Finally, analysis of 1152 Inuit, representing almost ~2% of the total Greenlandic Inuit population, showed that the frequency of the mutation was 1.0%. We conclude that the BRCA1 nucleotide 234 T > G is a common Greenlandic Inuit founder mutation. The relative high frequency in the general population, together with the ease of screening and possibility to reduce mortality in gene carriers, may warrant screening of the Greenlandic Inuit population. Provided screening is efficient, about 5% of breast- and 13% of ovarian cancers, respectively, may be prevented.

Keywords

BRCA1 RING domain Cys39Gly SNP array Greenland Inuit Founder mutation 

Notes

Acknowledgements

Nina Ilsøe, Bettina M. Andersen, Karina Nørgaard and Lis Krüger are acknowledged for excellent technical assistance. This study was supported by the Neye Foundation.

Supplementary material

10549_2008_60_MOESM1_ESM.pdf (752 kb)
(PDF 751 kb)

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Copyright information

© Springer Science+Business Media, LLC. 2008

Authors and Affiliations

  • Thomas v. O. Hansen
    • 1
    Email author
  • Bent Ejlertsen
    • 2
  • Anders Albrechtsen
    • 3
  • Eva Bergsten
    • 2
  • Peter Bjerregaard
    • 4
  • Torben Hansen
    • 5
  • Torben Myrhøj
    • 6
  • Peter B. Nielsen
    • 1
  • Vera Timmermans-Wielenga
    • 7
  • Mette K. Andersen
    • 8
  • Lars Jønson
    • 1
  • Finn C. Nielsen
    • 1
  1. 1.Department of Clinical Biochemistry 4111RigshospitaletCopenhagenDenmark
  2. 2.Department of OncologyRigshospitaletCopenhagenDenmark
  3. 3.Department of BiostatisticsUniversity of CopenhagenCopenhagenDenmark
  4. 4.National Institute of Public HealthCopenhagenDenmark
  5. 5.Steno Diabetes CenterGentofteDenmark
  6. 6.Department of SurgeryDronning Ingrids HospitalNuukGreenland
  7. 7.Department of PathologyRigshospitaletCopenhagenDenmark
  8. 8.Department of Clinical GeneticsJuliane Marie Center, RigshospitaletCopenhagenDenmark

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