Characterization of BRCA1 and BRCA2 deleterious mutations and variants of unknown clinical significance in unilateral and bilateral breast cancer: the WECARE study.
(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)
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- organization
- publishing date
- 2010
- type
- Contribution to journal
- publication status
- published
- subject
- in
- Human Mutation
- volume
- 31
- pages
- 1200 - 1240
- publisher
- John Wiley & Sons Inc.
- external identifiers
-
- wos:000279981700003
- pmid:20104584
- scopus:77149138300
- ISSN
- 1059-7794
- DOI
- 10.1002/humu.21202
- language
- English
- LU publication?
- yes
- id
- 89b11d81-4271-4a5d-ae53-32e1a35c2944 (old id 1540553)
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- http://www.ncbi.nlm.nih.gov/pubmed/20104584?dopt=Abstract
- date added to LUP
- 2016-04-04 08:22:07
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@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 Inc.}},
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}},
doi = {{10.1002/humu.21202}},
volume = {{31}},
year = {{2010}},
}