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. 2010 Nov;124(1):259-64. doi: 10.1007/s10549-010-0909-9. Epub 2010 May 1.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • BRCA1 Protein / genetics*
  • Base Sequence
  • Breast Neoplasms / ethnology
  • Breast Neoplasms / genetics*
  • Codon, Nonsense
  • DNA Mutational Analysis
  • Female
  • Founder Effect
  • Frameshift Mutation*
  • Genetic Predisposition to Disease
  • Genetic Testing
  • Greenland
  • Heredity
  • Humans
  • Inuit / genetics*
  • Middle Aged
  • Molecular Sequence Data
  • Ovarian Neoplasms / ethnology
  • Ovarian Neoplasms / genetics*
  • Pedigree
  • Risk Assessment
  • Risk Factors
  • Sequence Deletion*

Substances

  • BRCA1 Protein
  • BRCA1 protein, human
  • Codon, Nonsense