Genetic analysis of eight breast-ovarian cancer families with suspected BRCA1 mutations.

Fergus J Couch, J. Garber, S. Kiousis, K. Calzone, E. R. Hauser, S. D. Merajver, T. S. Frank, M. Boehnke, J. S. Chamberlain, F. S. Collins

Research output: Contribution to journalArticle

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Abstract

BRCA1 is a breast cancer-related tumor suppressor gene located on human chromosome 17q21. Inherited mutations in BRCA1 are thought to be responsible for approximately half of all inherited breast cancer and to confer increased risk for ovarian, colon, or prostate cancer. Studies of affected families and population-based studies have provided some information on the prevalence of BRCA1 mutations in Caucasian U.S. and European populations as well as on the penetrance of these mutations. We review the available data on the epidemiology of breast cancer with specific reference to BRCA1. In addition, we describe the genetic analysis of one large family with multiple affected individuals now known to harbor a BRCA1 germline mutation but initially identified by genetic linkage analysis. This family is presented as a model of the challenges that can be encountered in genetic analysis of familial forms of cancer. To this end, we compare the outcome of analysis before and after the identification of a mutation that predisposes family members to early-onset breast and ovarian cancers. We describe seven additional families with evidence of linkage between breast cancer and genetic markers in the BRCA1 region. Each of these families generated a 2-point LOD (i.e., logarithm of the odds) score greater than 1.18 for at least one polymorphic marker flanking BRCA1. These families have formed the basis of our efforts to characterize BRCA1 mutations. First-pass mutation analysis using the single-strand conformation polymorphism approach failed to identify any mutations in the seven families. We consider the possible reasons for the apparent low mutation-detection efficiency.

Original languageEnglish (US)
Pages (from-to)9-14
Number of pages6
JournalJournal of the National Cancer Institute. Monographs
Issue number17
StatePublished - 1995
Externally publishedYes

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Ovarian Neoplasms
Breast Neoplasms
Mutation
Genetic Linkage
Penetrance
Germ-Line Mutation
Human Chromosomes
Tumor Suppressor Genes
Genetic Markers
Colonic Neoplasms
Population
Prostatic Neoplasms
Epidemiology
Neoplasms

Cite this

Couch, F. J., Garber, J., Kiousis, S., Calzone, K., Hauser, E. R., Merajver, S. D., ... Collins, F. S. (1995). Genetic analysis of eight breast-ovarian cancer families with suspected BRCA1 mutations. Journal of the National Cancer Institute. Monographs, (17), 9-14.

Genetic analysis of eight breast-ovarian cancer families with suspected BRCA1 mutations. / Couch, Fergus J; Garber, J.; Kiousis, S.; Calzone, K.; Hauser, E. R.; Merajver, S. D.; Frank, T. S.; Boehnke, M.; Chamberlain, J. S.; Collins, F. S.

In: Journal of the National Cancer Institute. Monographs, No. 17, 1995, p. 9-14.

Research output: Contribution to journalArticle

Couch, FJ, Garber, J, Kiousis, S, Calzone, K, Hauser, ER, Merajver, SD, Frank, TS, Boehnke, M, Chamberlain, JS & Collins, FS 1995, 'Genetic analysis of eight breast-ovarian cancer families with suspected BRCA1 mutations.', Journal of the National Cancer Institute. Monographs, no. 17, pp. 9-14.
Couch, Fergus J ; Garber, J. ; Kiousis, S. ; Calzone, K. ; Hauser, E. R. ; Merajver, S. D. ; Frank, T. S. ; Boehnke, M. ; Chamberlain, J. S. ; Collins, F. S. / Genetic analysis of eight breast-ovarian cancer families with suspected BRCA1 mutations. In: Journal of the National Cancer Institute. Monographs. 1995 ; No. 17. pp. 9-14.
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abstract = "BRCA1 is a breast cancer-related tumor suppressor gene located on human chromosome 17q21. Inherited mutations in BRCA1 are thought to be responsible for approximately half of all inherited breast cancer and to confer increased risk for ovarian, colon, or prostate cancer. Studies of affected families and population-based studies have provided some information on the prevalence of BRCA1 mutations in Caucasian U.S. and European populations as well as on the penetrance of these mutations. We review the available data on the epidemiology of breast cancer with specific reference to BRCA1. In addition, we describe the genetic analysis of one large family with multiple affected individuals now known to harbor a BRCA1 germline mutation but initially identified by genetic linkage analysis. This family is presented as a model of the challenges that can be encountered in genetic analysis of familial forms of cancer. To this end, we compare the outcome of analysis before and after the identification of a mutation that predisposes family members to early-onset breast and ovarian cancers. We describe seven additional families with evidence of linkage between breast cancer and genetic markers in the BRCA1 region. Each of these families generated a 2-point LOD (i.e., logarithm of the odds) score greater than 1.18 for at least one polymorphic marker flanking BRCA1. These families have formed the basis of our efforts to characterize BRCA1 mutations. First-pass mutation analysis using the single-strand conformation polymorphism approach failed to identify any mutations in the seven families. We consider the possible reasons for the apparent low mutation-detection efficiency.",
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