A collaborative survey of 80 mutations in the BRCA1 breast and ovarian cancer susceptibility gene: Implications for presymptomatic testing and screening

D. Shattuck-Eidens, M. McClure, J. Simard, F. Labrie, S. Narod, Fergus J Couch, K. Hoskins, B. Weber, L. Castilla, M. Erdos, L. Brody, L. Friedman, E. Ostermeyer, C. Szabo, M. C. King, S. Jhanwar, K. Offit, L. Norton, D. E. Goldgar

Research output: Contribution to journalArticle

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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 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.

Original languageEnglish (US)
Pages (from-to)535-541
Number of pages7
JournalJournal of the American Medical Association
Volume273
Issue number7
StatePublished - 1995
Externally publishedYes

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Neoplasm Genes
Ovarian Neoplasms
Breast Neoplasms
Mutation
Surveys and Questionnaires
BRCA1 Gene
DNA
Mutation Rate
North America
Routine Diagnostic Tests

ASJC Scopus subject areas

  • Medicine(all)

Cite this

A collaborative survey of 80 mutations in the BRCA1 breast and ovarian cancer susceptibility gene : Implications for presymptomatic testing and screening. / Shattuck-Eidens, D.; McClure, M.; Simard, J.; Labrie, F.; Narod, S.; Couch, Fergus J; Hoskins, K.; Weber, B.; Castilla, L.; Erdos, M.; Brody, L.; Friedman, L.; Ostermeyer, E.; Szabo, C.; King, M. C.; Jhanwar, S.; Offit, K.; Norton, L.; Goldgar, D. E.

In: Journal of the American Medical Association, Vol. 273, No. 7, 1995, p. 535-541.

Research output: Contribution to journalArticle

Shattuck-Eidens, D, McClure, M, Simard, J, Labrie, F, Narod, S, Couch, FJ, Hoskins, K, Weber, B, Castilla, L, Erdos, M, Brody, L, Friedman, L, Ostermeyer, E, Szabo, C, King, MC, Jhanwar, S, Offit, K, Norton, L & Goldgar, DE 1995, 'A collaborative survey of 80 mutations in the BRCA1 breast and ovarian cancer susceptibility gene: Implications for presymptomatic testing and screening', Journal of the American Medical Association, vol. 273, no. 7, pp. 535-541.
Shattuck-Eidens, D. ; McClure, M. ; Simard, J. ; Labrie, F. ; Narod, S. ; Couch, Fergus J ; Hoskins, K. ; Weber, B. ; Castilla, L. ; Erdos, M. ; Brody, L. ; Friedman, L. ; Ostermeyer, E. ; Szabo, C. ; King, M. C. ; Jhanwar, S. ; Offit, K. ; Norton, L. ; Goldgar, D. E. / A collaborative survey of 80 mutations in the BRCA1 breast and ovarian cancer susceptibility gene : Implications for presymptomatic testing and screening. In: Journal of the American Medical Association. 1995 ; Vol. 273, No. 7. pp. 535-541.
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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 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.",
author = "D. Shattuck-Eidens and M. McClure and J. Simard and F. Labrie and S. Narod and Couch, {Fergus J} and K. Hoskins and B. Weber and L. Castilla and M. Erdos and L. Brody and L. Friedman and E. Ostermeyer and C. Szabo and King, {M. C.} and S. Jhanwar and K. Offit and L. Norton and Goldgar, {D. E.}",
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T1 - A collaborative survey of 80 mutations in the BRCA1 breast and ovarian cancer susceptibility gene

T2 - Implications for presymptomatic testing and screening

AU - Shattuck-Eidens, D.

AU - McClure, M.

AU - Simard, J.

AU - Labrie, F.

AU - Narod, S.

AU - Couch, Fergus J

AU - Hoskins, K.

AU - Weber, B.

AU - Castilla, L.

AU - Erdos, M.

AU - Brody, L.

AU - Friedman, L.

AU - Ostermeyer, E.

AU - Szabo, C.

AU - King, M. C.

AU - Jhanwar, S.

AU - Offit, K.

AU - Norton, L.

AU - Goldgar, D. E.

PY - 1995

Y1 - 1995

N2 - 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.

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