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A Collaborative Survey of 80 Mutations in the BRCA1 Breast and Ovarian Cancer Susceptibility Gene : Implications for Presymptomatic Testing and Screening

Shattuck Eidens, Donna ; Mcclure, Melody ; Simard, Jacques ; Labrie, Fernand ; Narod, Steve ; Couch, Fergus ; Hoskins, Kent ; Weber, Barbara ; Castilla, Lucio and Erdos, Mike , et al. (1995) In JAMA: The Journal of the American Medical Association 273(7). p.535-541
Abstract
OBJECTIVES:
To report the initial experience of an international group of investigators in identifying mutations in the BRCA1 breast and ovarian cancer susceptibility gene, to assess the spectrum of such mutations in samples from patients with different family histories of cancer, and to determine the frequency of recurrent mutations.
DESIGN:
Nine laboratories in North America and the United Kingdom tested for BRCA1 mutations in DNA samples obtained from a total of 372 unrelated patients with breast or ovarian cancer largely chosen from high-risk families. Three of these laboratories also analyzed a total of 714 additional samples from breast or ovarian cancer cases, including 557 unselected for family history, for two specific... (More)
OBJECTIVES:
To report the initial experience of an international group of investigators in identifying mutations in the BRCA1 breast and ovarian cancer susceptibility gene, to assess the spectrum of such mutations in samples from patients with different family histories of cancer, and to determine the frequency of recurrent mutations.
DESIGN:
Nine laboratories in North America and the United Kingdom tested for BRCA1 mutations in DNA samples obtained from a total of 372 unrelated patients with breast or ovarian cancer largely chosen from high-risk families. Three of these laboratories also analyzed a total of 714 additional samples from breast or ovarian cancer cases, including 557 unselected for family history, for two specific mutations that had been found to recur in familial samples.
PARTICIPANTS:
A total of 1086 women with either breast or ovarian cancer.
MAIN OUTCOME MEASURE:
The detection of sequence variation in patients' DNA samples that is not found in sets of control samples.
RESULTS:
BRCA1 mutations have now been identified in a total of 80 patient samples. Thirty-eight distinct mutations were found among 63 mutations identified through a complete screen of the BRCA1 gene. Three specific mutations appeared relatively common, occurring eight, seven, and five times, respectively. When specific tests for the two most common mutations were performed in larger sets of samples, they were found in 17 additional patients. Mutations predicted to result in a truncated protein accounted for 86% of the mutations detected by complete screening.
CONCLUSIONS:
The high frequency of protein-terminating mutations and the observation of many recurrent mutations found in a diverse set of samples could lead to a relatively simple diagnostic test for BRCA1 mutations. More data must be accumulated to address specifically the sensitivity and specificity of such a diagnostic testing procedure and to better estimate the age-specific risk for breast and ovarian cancer associated with such mutations. (Less)
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organization
publishing date
type
Contribution to journal
publication status
published
subject
in
JAMA: The Journal of the American Medical Association
volume
273
issue
7
pages
535 - 541
publisher
American Medical Association
external identifiers
  • scopus:0028834145
  • pmid:7837387
ISSN
0098-7484
DOI
10.1001/jama.1995.03520310033026
language
English
LU publication?
yes
id
241a0117-9f79-4ef1-9452-644540fd6ff4
date added to LUP
2019-10-25 13:39:55
date last changed
2024-01-01 22:51:34
@article{241a0117-9f79-4ef1-9452-644540fd6ff4,
  abstract     = {{OBJECTIVES:<br/>To report the initial experience of an international group of investigators in identifying mutations in the BRCA1 breast and ovarian cancer susceptibility gene, to assess the spectrum of such mutations in samples from patients with different family histories of cancer, and to determine the frequency of recurrent mutations.<br/>DESIGN:<br/>Nine laboratories in North America and the United Kingdom tested for BRCA1 mutations in DNA samples obtained from a total of 372 unrelated patients with breast or ovarian cancer largely chosen from high-risk families. Three of these laboratories also analyzed a total of 714 additional samples from breast or ovarian cancer cases, including 557 unselected for family history, for two specific mutations that had been found to recur in familial samples.<br/>PARTICIPANTS:<br/>A total of 1086 women with either breast or ovarian cancer.<br/>MAIN OUTCOME MEASURE:<br/>The detection of sequence variation in patients' DNA samples that is not found in sets of control samples.<br/>RESULTS:<br/>BRCA1 mutations have now been identified in a total of 80 patient samples. Thirty-eight distinct mutations were found among 63 mutations identified through a complete screen of the BRCA1 gene. Three specific mutations appeared relatively common, occurring eight, seven, and five times, respectively. When specific tests for the two most common mutations were performed in larger sets of samples, they were found in 17 additional patients. Mutations predicted to result in a truncated protein accounted for 86% of the mutations detected by complete screening.<br/>CONCLUSIONS:<br/>The high frequency of protein-terminating mutations and the observation of many recurrent mutations found in a diverse set of samples could lead to a relatively simple diagnostic test for BRCA1 mutations. More data must be accumulated to address specifically the sensitivity and specificity of such a diagnostic testing procedure and to better estimate the age-specific risk for breast and ovarian cancer associated with such mutations.}},
  author       = {{Shattuck Eidens, Donna and Mcclure, Melody and Simard, Jacques and Labrie, Fernand and Narod, Steve and Couch, Fergus and Hoskins, Kent and Weber, Barbara and Castilla, Lucio and Erdos, Mike and Brody, Lawrence and Friedman, Lori and Ostermeyer, Elizabeth and Szabo, Csilla and King, Mary Claire and Jhanwar, Suresh and Offit, Kenneth and Norton, Larry and Gilewski, Teresa and Lubin, Mathew and Osborne, Michael and Black, Donald and Boyd, Marie and Steel, Michael and Ingles, Sue and Haile, Robert and Lindblom, Annika and Olsson, Hakan and Borg, Ake and Bishop, D. Timothy and Solomon, Ellen and Radice, Paolo and Spatti, Giovanbattista and Gayther, Simon and Ponder, Bruce and Warren, William and Stratton, Mike and Liu, Qingyun and Fujimura, Frank and Lewis, Cathryn and Skolnick, Mark H. and Goldgar, David E.}},
  issn         = {{0098-7484}},
  language     = {{eng}},
  month        = {{01}},
  number       = {{7}},
  pages        = {{535--541}},
  publisher    = {{American Medical Association}},
  series       = {{JAMA: The Journal of the American Medical Association}},
  title        = {{A Collaborative Survey of 80 Mutations in the BRCA1 Breast and Ovarian Cancer Susceptibility Gene : Implications for Presymptomatic Testing and Screening}},
  url          = {{http://dx.doi.org/10.1001/jama.1995.03520310033026}},
  doi          = {{10.1001/jama.1995.03520310033026}},
  volume       = {{273}},
  year         = {{1995}},
}