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

• Published in: Breast Cancer Research and Treatment
• Language: English
• Published: Springer US 2010
• Subjects: BRCA1; Greenland; Inuit; Novel mutation; Nuuk; Finn; greenlandic; inuit; inuits
• Online Access: http://hdl.handle.net/2262/42410; https://doi.org/10.1007/s10549-010-0909-9

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. [e-mail] (Hansen, Thomas v. O.) Department of Clinical Biochemistry, Rigshospitalet - 4111, Blegdamsvej 9 - 2100 - Copenhagen - DENMARK (Hansen, Thomas v. O.) Department of Clinical Biochemistry, Rigshospitalet - 4111, Blegdamsvej 9 - 2100 - Copenhagen - DENMARK (J?nson, Lars) Department of Biostatistics, University of Copenhagen - ?ster Farimagsgade 5 - 1014 - Copenhagen - DENMARK (Albrechtsen, Anders) Department of Clinical Biochemistry, Rigshospitalet - 4111, Blegdamsvej 9 - 2100 - Copenhagen - DENMARK (Steffensen, Ane Y.) Department of Oncology, Rigshospitalet - Blegdamsvej 9 - 2100 - Copenhagen - DENMARK (Bergsten, Eva) Department of Surgery, Dronning Ingrids Hospital - Postbox 3333 - 3900 - Nuuk - GREENLAND (Myrh?j, Torben) Department of Oncology, Rigshospitalet - Blegdamsvej 9 - 2100 - Copenhagen - DENMARK (Ejlertsen, Bent) Department of Clinical Biochemistry, Rigshospitalet - 4111, Blegdamsvej 9 - 2100 - Copenhagen - DENMARK (Nielsen, Finn C.) DENMARK GREENLAND Registration: 2010-04-19 Received: 2010-03-29 Accepted: 2010-04-19 ePublished: 2010-05-01