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Characterization of BRCA1 and BRCA2 deleterious mutations and variants of unknown clinical significance in unilateral and bilateral breast cancer: the WECARE study.

  • Åke Borg
  • Robert W Haile
  • Kathleen E Malone
  • Marinela Capanu
  • Ahn Diep
  • Therese Törngren
  • Sharon Teraoka
  • Colin B Begg
  • Duncan C Thomas
  • Patrick Concannon
  • Lene Mellemkjaer
  • Leslie Bernstein
  • Lina Tellhed
  • Shanyan Xue
  • Eric R Olson
  • Xiaolin Liang
  • Jessica Dolle
  • Anne-Lise Børresen-Dale
  • Jonine L Bernstein
Publishing year: 2010
Language: English
Pages: 1200-1240
Publication/Series: Human Mutation
Volume: 31
Document type: Journal article
Publisher: John Wiley & Sons

Abstract english

BRCA1 and BRCA2 screening in women at high-risk of breast cancer results in the identification of both unambiguously defined deleterious mutations and sequence variants of unknown clinical significance (VUS). We examined a population-based sample of young women with contralateral breast cancer (CBC, n=705) or unilateral breast cancer (UBC, n=1398). We identified 470 unique sequence variants, of which 113 were deleterious mutations. The remaining 357 VUS comprised 185 unique missense changes, 60% were observed only once, while 3% occurred with a frequency of >10%. Deleterious mutations occurred three times more often in women with CBC (15.3%) than in women with UBC (5.2%), whereas combined, VUS were observed in similar frequencies in women with CBC and UBC. A protein alignment algorithm defined 16 rare VUS, occurring at highly conserved residues and/or conferring a considerable biochemical difference, the majority located in the BRCA2 DNA-binding domain. We confirm a multiplicity of BRCA1 and BRCA2 VUS that occur at a wide range of allele frequencies. Although some VUS inflict chemical differences at conserved residues, suggesting a deleterious effect, the majority are not associated with an increased risk of CBC. (c) 2010 Wiley-Liss, Inc.


  • Medical Genetics


  • CREATE Health
  • Familial Breast Cancer
  • ISSN: 1059-7794
Åke Borg
Åke Borg
E-mail: ake [dot] borg [at] med [dot] lu [dot] se

Principal investigator

Oncology and Pathology, MV

+46 46 275 25 52

MV 404 C21B2


Project manager

Familial Breast Cancer



Oncology and Pathology, MV

MV 404 C21C2