Identification of a novel 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

Thomas V. O. Hansen (1) , Lars Jønson (1) , Anders Albrechtsen (2) , Ane Y. Steffensen (1) , Eva Bergsten (3) , Torben Myrhøj (4) , Bent Ejlertsen (3) , Finn C. Nielsen (1)

1 Department of Clinical Biochemistry [Rigshospitalet]
2 Section of Biostatistics [Copenhagen]
3 Department of Oncology
4 Department of Surgery

Germ-line mutations in the tumour suppressor proteins and predispose to breast and ovarian cancer. We have recently identified a Greenlandic Inuit nucleotide 234T>G/c.115T>G (p.Cys39Gly) founder mutation, which at that time was the only disease-causing mutation identified in this population. Here, we describe the identification of a novel disease-causing 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 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 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 gene.

Mots clés: Greenland; Inuit; Novel mutation

Thomas V. O. Hansen, Lars Jønson, Anders Albrechtsen, Ane Y. Steffensen, Eva Bergsten, et al.. Identification of a novel 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 Research and Treatment, 2010, 124 (1), pp.259-264. ⟨10.1007/s10549-010-0909-9⟩. ⟨hal-00531008⟩