A high incidence of BRCA1 mutations in 20 breast-ovarian cancer families

Olga Serova, Marco Montagna, Delphine Torchard, Steven A. Narod, Patricia Tonin, Bakary Sylla, Henry T. Lynch, Jean Feunteun, Gilbert M. Lenoir

Research output: Contribution to journalArticle

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Abstract

We have analyzed 20 breast-ovarian cancer families, the majority of which show positive evidence of linkage to chromosome 17q12, for germ-line mutations in the BRCA1 gene. BRCA1 mutations cosegregating with breast and ovarian cancer susceptibility were identified in 16 families, including 1 family with a case of male breast cancer. Nine of these mutations have not been reported previously. The majority of mutations were found to generate a premature stop codon leading to the formation of a truncated BRCA1 protein of 2%-88% of the expected normal length. Two mutations altered the RING finger domain. Sequencing of genomic DNA led to the identification of a mutation in the coding region of BRCA1 in 12 families, and cDNA analysis revealed an abnormal or missing BRCA1 transcript in 4 of the 8 remaining families. A total of eight mutations were associated with a reduced quantity of BRCA1 transcript. We were unable to detect BRCA1 mutations in 4 of the 20 families, but only 1 of these was clearly linked to BRCA1. It is expected that the majority of clear examples of the breast-ovarian cancer syndrome will be associated with germ-line mutations in the coding region of BRCA1.

Original languageEnglish
Pages (from-to)42-51
Number of pages10
JournalAmerican Journal of Human Genetics
Volume58
Issue number1
StatePublished - 1996

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Ovarian Neoplasms
Breast Neoplasms
Mutation
Incidence
Germ-Line Mutation
RING Finger Domains
BRCA1 Protein
Male Breast Neoplasms
BRCA1 Gene
Nonsense Codon
DNA Sequence Analysis
Complementary DNA
Chromosomes

All Science Journal Classification (ASJC) codes

  • Genetics

Cite this

Serova, O., Montagna, M., Torchard, D., Narod, S. A., Tonin, P., Sylla, B., ... Lenoir, G. M. (1996). A high incidence of BRCA1 mutations in 20 breast-ovarian cancer families. American Journal of Human Genetics, 58(1), 42-51.

A high incidence of BRCA1 mutations in 20 breast-ovarian cancer families. / Serova, Olga; Montagna, Marco; Torchard, Delphine; Narod, Steven A.; Tonin, Patricia; Sylla, Bakary; Lynch, Henry T.; Feunteun, Jean; Lenoir, Gilbert M.

In: American Journal of Human Genetics, Vol. 58, No. 1, 1996, p. 42-51.

Research output: Contribution to journalArticle

Serova, O, Montagna, M, Torchard, D, Narod, SA, Tonin, P, Sylla, B, Lynch, HT, Feunteun, J & Lenoir, GM 1996, 'A high incidence of BRCA1 mutations in 20 breast-ovarian cancer families', American Journal of Human Genetics, vol. 58, no. 1, pp. 42-51.
Serova O, Montagna M, Torchard D, Narod SA, Tonin P, Sylla B et al. A high incidence of BRCA1 mutations in 20 breast-ovarian cancer families. American Journal of Human Genetics. 1996;58(1):42-51.
Serova, Olga ; Montagna, Marco ; Torchard, Delphine ; Narod, Steven A. ; Tonin, Patricia ; Sylla, Bakary ; Lynch, Henry T. ; Feunteun, Jean ; Lenoir, Gilbert M. / A high incidence of BRCA1 mutations in 20 breast-ovarian cancer families. In: American Journal of Human Genetics. 1996 ; Vol. 58, No. 1. pp. 42-51.
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