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Cancer predisposing BARD1 mutations in breast-ovarian cancer families

Ratajska, Magdalena; Antoszewska, Ewelina; Piskorz, Anna; Brozek, Izabela; Borg, Åke LU ; Kusmierek, Hanna; Biernat, Wojciech and Limon, Janusz (2012) In Breast Cancer Research and Treatment 131(1). p.89-97
Abstract
The breast cancer susceptibility gene BARD1 (BRCA1-associated RING domain protein, MIM# 601593) acts with BRCA1 in DNA double-strand break (DSB) repair and also in apoptosis initiation. We screened 109 BRCA1/2 negative high-risk breast and/or ovarian cancer patients from North-Eastern Poland for BARD1 germline mutations using a combination of denaturing high-performance liquid chromatography and direct sequencing. We identified 16 different BARD1 sequence variants, five of which are novel. Three of them were suspected to be pathogenic, including a protein truncating nonsense mutation (c.1690C > T, p.Gln564X), a splice mutation (c.1315-2A > G) resulting in exon 5 skipping, and a silent change (c.1977A > G) which alters several... (More)
The breast cancer susceptibility gene BARD1 (BRCA1-associated RING domain protein, MIM# 601593) acts with BRCA1 in DNA double-strand break (DSB) repair and also in apoptosis initiation. We screened 109 BRCA1/2 negative high-risk breast and/or ovarian cancer patients from North-Eastern Poland for BARD1 germline mutations using a combination of denaturing high-performance liquid chromatography and direct sequencing. We identified 16 different BARD1 sequence variants, five of which are novel. Three of them were suspected to be pathogenic, including a protein truncating nonsense mutation (c.1690C > T, p.Gln564X), a splice mutation (c.1315-2A > G) resulting in exon 5 skipping, and a silent change (c.1977A > G) which alters several exonic splicing enhancer motifs in exon 10 and results in a transcript lacking exons 2-9. Our findings suggest that BARD1 mutations may be regarded as cancer risk alleles and warrant further investigation to determine their actual contribution to non-BRCA1/2 breast and ovarian cancer families. (Less)
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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
Breast cancer, Ovarian cancer, Hereditary, BARD1 mutation
in
Breast Cancer Research and Treatment
volume
131
issue
1
pages
89 - 97
publisher
Springer
external identifiers
  • wos:000298006300009
  • scopus:84856210264
ISSN
1573-7217
DOI
10.1007/s10549-011-1403-8
language
English
LU publication?
yes
id
cb0fed17-4dc4-46fd-b61a-5eee85ee81f0 (old id 2362693)
date added to LUP
2012-03-01 12:19:02
date last changed
2017-10-01 04:18:19
@article{cb0fed17-4dc4-46fd-b61a-5eee85ee81f0,
  abstract     = {The breast cancer susceptibility gene BARD1 (BRCA1-associated RING domain protein, MIM# 601593) acts with BRCA1 in DNA double-strand break (DSB) repair and also in apoptosis initiation. We screened 109 BRCA1/2 negative high-risk breast and/or ovarian cancer patients from North-Eastern Poland for BARD1 germline mutations using a combination of denaturing high-performance liquid chromatography and direct sequencing. We identified 16 different BARD1 sequence variants, five of which are novel. Three of them were suspected to be pathogenic, including a protein truncating nonsense mutation (c.1690C > T, p.Gln564X), a splice mutation (c.1315-2A > G) resulting in exon 5 skipping, and a silent change (c.1977A > G) which alters several exonic splicing enhancer motifs in exon 10 and results in a transcript lacking exons 2-9. Our findings suggest that BARD1 mutations may be regarded as cancer risk alleles and warrant further investigation to determine their actual contribution to non-BRCA1/2 breast and ovarian cancer families.},
  author       = {Ratajska, Magdalena and Antoszewska, Ewelina and Piskorz, Anna and Brozek, Izabela and Borg, Åke and Kusmierek, Hanna and Biernat, Wojciech and Limon, Janusz},
  issn         = {1573-7217},
  keyword      = {Breast cancer,Ovarian cancer,Hereditary,BARD1 mutation},
  language     = {eng},
  number       = {1},
  pages        = {89--97},
  publisher    = {Springer},
  series       = {Breast Cancer Research and Treatment},
  title        = {Cancer predisposing BARD1 mutations in breast-ovarian cancer families},
  url          = {http://dx.doi.org/10.1007/s10549-011-1403-8},
  volume       = {131},
  year         = {2012},
}