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
• Main Authors: Hansen, Thomas van Overeem, Jønson, Lars, Albrechtsen, Anders, Steffensen, Ane Yde, Bergsten, Eva Boje, Myrhøj, Torben, Ejlertsen, Bent Laursen, Nielsen, Finn Cilius
• Format: Article in Journal/Newspaper
• Language: English
• Published: 2010
• Subjects: Adult; BRCA1 Protein; Base Sequence; Breast Neoplasms; Codon; Nonsense; DNA Mutational Analysis; Female; Founder Effect; Frameshift Mutation; Genetic Predisposition to Disease; Genetic Testing; Greenland; Heredity; Humans; Inuits; Middle Aged; Molecular Sequence Data; Ovarian Neoplasms; Pedigree; Risk Assessment; Risk Factors; Sequence Deletion; greenlandic; inuit; inuits
• Online Access: https://curis.ku.dk/portal/da/publications/identification-of-a-novel-brca1-nucleotide-4803delccc4684delcc-mutation-and-a-nucleotide-249tac130ta-pcys44ser-mutation-in-two-greenlandic-inuit-families(997f5ff0-41ed-4700-88f0-4c98a35c3f14).html; https://doi.org/10.1007/s10549-010-0909-9

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.