title: De novo Alu element insertions targeted to a sequence common to the BRCA1 and BRCA2 genes.
abstract: Linkage analysis suggests that mutations in the BRCA1 and BRCA2 genes are responsible for cancer predisposition in more than 80% of the families with high incidence of breast/ovarian cancer. However, pathogenic mutations in the BRCA1/2 genes are generally identified in much less than half of the families investigated in a diagnostic setting with the currently used PCR-based screening protocols. Here we report the identification of two different de novo Alu element insertions within the BRCA1/2 coding sequences in three out of the 50 families in which we found a cancer predisposing mutation, suggesting that this type of mutation is much more common than suggested by their occurrence in mutation databases. The Alu insertion in the BRCA2 gene resulted in the removal of the targeted exon from the corresponding mRNA molecule. Unexpectedly the Target Site Duplications generated by both Alu element insertions contained a specific 9 bp long segment, which might eventually serve as a recognition site for the transposition machinery. Finally, in contrast to the disease causing Alu insertions reported to date, the transposon identified in the BRCA1 gene does not belong to a "young" AluY but to an AluS subfamily, indicating that some of these "old" Alu elements, which are supposed to be non-functional fossil relics, are still able to retrotranspose in vivo.
authors.affiliation: Laboratory of Molecular and Medical Oncology, AZ-VUB, Vrije Universiteit Brussel, Laarbeeklaan 101, B1090 Brussels, Belgium. eteugels@az.vub.ac.be
authors.forename: Erik
authors.initials: E
authors.lastname: Teugels
authors.forename: Sylvia
authors.initials: S
authors.lastname: De Brakeleer
authors.forename: Guido
authors.initials: G
authors.lastname: Goelen
authors.forename: Willy
authors.initials: W
authors.lastname: Lissens
authors.forename: Erica
authors.initials: E
authors.lastname: Sermijn
authors.forename: Jacques
authors.initials: J
authors.lastname: De Grève
mesh_terms: D020087:Alu Elements; D001483:Base Sequence; D001943:Breast Neoplasms / Q000235:genetics; D018450:Disease Progression; D005260:Female; D019398:Genes, BRCA1; D024522:Genes, BRCA2; D008040:Genetic Linkage; D006801:Humans; D008297:Male; D008969:Molecular Sequence Data; D010051:Ovarian Neoplasms / Q000235:genetics; D018626:Retroelements / Q000235:genetics; D012689:Sequence Homology, Nucleic Acid; D012737:Sex Factors
chemical_list: D018626:Retroelements