Advanced

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

Borg, Åke LU ; Haile, Robert W; Malone, Kathleen E; Capanu, Marinela; Diep, Ahn; Törngren, Therese LU ; Teraoka, Sharon; Begg, Colin B; Thomas, Duncan C and Concannon, Patrick, et al. (2010) In Human Mutation 31. p.1200-1240
Abstract
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... (More)
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. (Less)
Please use this url to cite or link to this publication:
author
, et al. (More)
(Less)
organization
publishing date
type
Contribution to journal
publication status
published
subject
in
Human Mutation
volume
31
pages
1200 - 1240
publisher
John Wiley & Sons
external identifiers
  • wos:000279981700003
  • pmid:20104584
  • scopus:77149138300
ISSN
1059-7794
DOI
10.1002/humu.21202
project
CREATE Health
language
English
LU publication?
yes
id
89b11d81-4271-4a5d-ae53-32e1a35c2944 (old id 1540553)
alternative location
http://www.ncbi.nlm.nih.gov/pubmed/20104584?dopt=Abstract
date added to LUP
2010-02-04 20:11:18
date last changed
2018-06-24 04:47:45
@article{89b11d81-4271-4a5d-ae53-32e1a35c2944,
  abstract     = {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.},
  author       = {Borg, Åke and Haile, Robert W and Malone, Kathleen E and Capanu, Marinela and Diep, Ahn and Törngren, Therese and Teraoka, Sharon and Begg, Colin B and Thomas, Duncan C and Concannon, Patrick and Mellemkjaer, Lene and Bernstein, Leslie and Tellhed, Lina and Xue, Shanyan and Olson, Eric R and Liang, Xiaolin and Dolle, Jessica and Børresen-Dale, Anne-Lise and Bernstein, Jonine L},
  issn         = {1059-7794},
  language     = {eng},
  pages        = {1200--1240},
  publisher    = {John Wiley & Sons},
  series       = {Human Mutation},
  title        = {Characterization of BRCA1 and BRCA2 deleterious mutations and variants of unknown clinical significance in unilateral and bilateral breast cancer: the WECARE study.},
  url          = {http://dx.doi.org/10.1002/humu.21202},
  volume       = {31},
  year         = {2010},
}