Screening for germ-line rearrangements and regulatory mutations in BRCA1 led to the identification of four new deletions

Nadine Puget, Dominique Stoppa-Lyonnet, Olga M. Sinilnikova, Sabine Pages̀, Henry T. Lynch, Gilbert M. Lenoir, Sylvie Mazoyer

Research output: Contribution to journalArticle

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Abstract

Most previous BRCA1 mutation screening studies conducted on breast cancer families were aimed at identifying mutations in the coding sequence and splice sites. Mutations in the promoter and untranslated regions, and large rearrangements are missed by standard mutation detection strategies. To look specifically for such germ-line mutations in the BRCA1 gene, we have analyzed a series of 27 American and 51 French breast cancer families in which no BRCA1 mutation was identified by classical techniques. No mutations were detected in either the promoter or untranslated regions, and we did not find any deletion of the whole gene. Four families were found to carry distinct deletions. Two of them, probably generated by Alu-mediated homologous recombination, were internal deletions of 3 and 23.8 kb, encompassing exon 15 and exons 8-13, respectively. These alterations both lead to a frameshift in the mutant mRNA and to premature stop codon-mediated mRNA decay. The other two deletions encompass exons 1 and 2. On the basis of previous and present analyses, rearrangements represent 8% (3/37) of all mutations in our set of BRCA1 American families. Consequently, the search for rearrangements appears mandatory in BRCA1 mutation screening studies.

Original languageEnglish
Pages (from-to)455-461
Number of pages7
JournalCancer Research
Volume59
Issue number2
StatePublished - Jan 16 1999

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Germ Cells
Mutation
Untranslated Regions
Exons
Genetic Promoter Regions
Breast Neoplasms
BRCA1 Gene
Germ-Line Mutation
Nonsense Codon
Homologous Recombination
RNA Stability
Gene Deletion
Messenger RNA

All Science Journal Classification (ASJC) codes

  • Cancer Research
  • Oncology

Cite this

Puget, N., Stoppa-Lyonnet, D., Sinilnikova, O. M., Pages̀, S., Lynch, H. T., Lenoir, G. M., & Mazoyer, S. (1999). Screening for germ-line rearrangements and regulatory mutations in BRCA1 led to the identification of four new deletions. Cancer Research, 59(2), 455-461.

Screening for germ-line rearrangements and regulatory mutations in BRCA1 led to the identification of four new deletions. / Puget, Nadine; Stoppa-Lyonnet, Dominique; Sinilnikova, Olga M.; Pages̀, Sabine; Lynch, Henry T.; Lenoir, Gilbert M.; Mazoyer, Sylvie.

In: Cancer Research, Vol. 59, No. 2, 16.01.1999, p. 455-461.

Research output: Contribution to journalArticle

Puget, N, Stoppa-Lyonnet, D, Sinilnikova, OM, Pages̀, S, Lynch, HT, Lenoir, GM & Mazoyer, S 1999, 'Screening for germ-line rearrangements and regulatory mutations in BRCA1 led to the identification of four new deletions', Cancer Research, vol. 59, no. 2, pp. 455-461.
Puget N, Stoppa-Lyonnet D, Sinilnikova OM, Pages̀ S, Lynch HT, Lenoir GM et al. Screening for germ-line rearrangements and regulatory mutations in BRCA1 led to the identification of four new deletions. Cancer Research. 1999 Jan 16;59(2):455-461.
Puget, Nadine ; Stoppa-Lyonnet, Dominique ; Sinilnikova, Olga M. ; Pages̀, Sabine ; Lynch, Henry T. ; Lenoir, Gilbert M. ; Mazoyer, Sylvie. / Screening for germ-line rearrangements and regulatory mutations in BRCA1 led to the identification of four new deletions. In: Cancer Research. 1999 ; Vol. 59, No. 2. pp. 455-461.
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