title: New mechanism of BRCA-1 mutation by deletion/insertion at the same nucleotide position in three unrelated French breast/ovarian cancer families.
abstract: A novel complex mutation consisting of a small deletion/insertion (3958del5ins4) was found in the breast cancer-1 gene (BRCA-1) in three unrelated French breast and/or ovarian cancer families. These mutations occurred at the same nucleotide position of the 3' end of exon 11. The wild-type sequence, CTCAG, was deleted and replaced by AGGC in the three families. The consequence is the generation of a stop codon, TAG, resulting in a truncated protein. We propose two different mechanisms to explain the generation of this complex mutation: (i) the simultaneous occurrence of a deletion and an insertion in a stem-loop structure and (ii) the abortive integration of a human transposable element (Tigger 1) that deleted 5 nucleotides and inserted a 4-nucleotide "scar", corresponding to the 5' extremity of the transposon.
authors.affiliation: Laboratory of Molecular Oncology, INSERM CRI 9502 and EA 2145, Centre Jean Perrin, BP 392, Clermont-Ferrand, France.
authors.forename: N
authors.initials: N
authors.lastname: Presneau
authors.forename: V
authors.initials: V
authors.lastname: Laplace-Marieze
authors.forename: V
authors.initials: V
authors.lastname: Sylvain
authors.forename: A
authors.initials: A
authors.lastname: Lortholary
authors.forename: A
authors.initials: A
authors.lastname: Hardouin
authors.forename: D
authors.initials: D
authors.lastname: Bernard-Gallon
authors.forename: Y J
authors.initials: YJ
authors.lastname: Bignon
mesh_terms: D019313:BRCA1 Protein / Q000235:genetics; D001943:Breast Neoplasms / Q000235:genetics*; D018388:Codon, Terminator / Q000235:genetics; D005260:Female; D005602:France; D019398:Genes, BRCA1 / Q000235:genetics*; D005819:Genetic Markers; D006239:Haplotypes; D006801:Humans; D008875:Middle Aged; D009154:Mutation / Q000235:genetics; D010051:Ovarian Neoplasms / Q000235:genetics*; D016133:Polymerase Chain Reaction; D017384:Sequence Deletion / Q000235:genetics
chemical_list: D019313:BRCA1 Protein; D018388:Codon, Terminator; D005819:Genetic Markers