1. BRCA1 genomic deletions are major founder mutations in Dutch breast cancer patients
- Author
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Hanne Meijers-Heijboer, Egbert Bakker, M.J.L. Ligtenberg, Anne Petrij-Bosch, Tamara Peelen, M. Drusedau, Cees J. Cornelisse, R. Olmer, Peter Devilee, S. Hageman, Hans F. A. Vasen, L.J. van 't Veer, Jan G. M. Klijn, G.J.B. van Ommen, Frans B. L. Hogervorst, Peer Arts, M. van Vliet, R. van Eijk, and Other departments
- Subjects
Genetic counseling ,Molecular Sequence Data ,Breast Neoplasms ,Deoxyribonuclease HindIII ,Biology ,medicine.disease_cause ,Polymerase Chain Reaction ,Exon ,Genetics ,medicine ,Humans ,De rol van chromosoomafwijkingen en (anti-)oncogenen in humane tumoren ,GeneralLiterature_REFERENCE(e.g.,dictionaries,encyclopedias,glossaries) ,Netherlands ,Repetitive Sequences, Nucleic Acid ,Sequence Deletion ,Ovarian Neoplasms ,Mutation ,Base Sequence ,BRCA1 Protein ,Point mutation ,Haplotype ,Single-strand conformation polymorphism ,Middle Aged ,Founder Effect ,Blotting, Southern ,genomic DNA ,Haplotypes ,Female ,The role of chromosomal aberrations and (anti-)oncogenes in human tumours ,Founder effect - Abstract
To date, more than 300 distinct small deletions, insertions and point mutations, mostly leading to premature termination of translation, have been reported in the breast/ovarian-cancer susceptibility gene BRCA1. The elevated frequencies of some mutations in certain ethnic subpopulations are caused by founder effects, rather than by mutation hotspots. Here we report that the currently available mutation spectrum of BRCA1 has been biased by PCR-based mutation-screening methods, such as SSCP, the protein truncation test (PTT) and direct sequencing, using genomic DNA as template. Three large genomic deletions that are not detected by these approaches comprise 36% of all BRCA1 mutations found in Dutch breast-cancer families to date. A 510-bp Alu-mediated deletion comprising exon 22 was found in 8 of 170 breast-cancer families recruited for research purposes and in 6 of 49 probands referred to the Amsterdam Family Cancer Clinic for genetic counselling. In addition, a 3,835-bp Alu-mediated deletion encompassing exon 13 was detected in 4 of 170 research families, while an deletion of approximately 14 kb was detected in a single family [corrected]. Haplotype analyses indicated that each recurrent deletion had a single common ancestor.
- Published
- 1997
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