Abstract
Germ-line mutations in the tumour suppressor proteins BRCA1 and BRCA2 predispose to breast and ovarian cancer. We have recently identified a Greenlandic Inuit BRCA1 nucleotide 234T>G/c.115T>G (p.Cys39Gly) founder mutation, which at that time was the only disease-causing BRCA1/BRCA2 mutation identified in this population. Here, we describe the identification of a novel disease-causing BRCA1 nucleotide 4803delCC/c.4684delCC mutation in a Greenlandic Inuit with ovarian cancer. The mutation introduces a frameshift and a premature stop at codon 1572. We have also identified a BRCA1 nucleotide 249T>A/c.130T>A (p.Cys44Ser) mutation in another Greenlandic individual with ovarian cancer. This patient share a 1–2 Mb genomic fragment, containing the BRCA1 gene, with four Danish families harbouring the same mutation, suggesting that the 249T>A/c.130T>A (p.Cys44Ser) mutation originates from a Danish ancestor. We conclude that screening of Greenlandic Inuits with high risk of breast or ovarian cancer should include sequencing of the entire BRCA1 gene.
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Acknowledgements
Berit Bak Jensen, Christina Berantzino, Jesper Andreasen, Jesper Johansson, Karina Nørgaard, Lis Krüger and Nina Ilsøe are thanked for BRCA1/BRCA2 screening of breast and/or ovarian cancer patients. The study was supported by the Neye Foundation.
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Hansen, T.v.O., Jønson, L., Albrechtsen, A. et al. Identification of a novel BRCA1 nucleotide 4803delCC/c.4684delCC mutation and a nucleotide 249T>A/c.130T>A (p.Cys44Ser) mutation in two Greenlandic Inuit families: implications for genetic screening of Greenlandic Inuit families with high risk for breast and/or ovarian cancer. Breast Cancer Res Treat 124, 259–264 (2010). https://doi.org/10.1007/s10549-010-0909-9
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DOI: https://doi.org/10.1007/s10549-010-0909-9