New mechanism of BRCA-1 mutation by deletion/insertion at the same nucleotide position in three unrelated French breast/ovarian cancer families

Hum Genet. 1998 Sep;103(3):334-9. doi: 10.1007/s004390050826.

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.

MeSH terms

  • BRCA1 Protein / genetics
  • Breast Neoplasms / genetics*
  • Codon, Terminator / genetics
  • Female
  • France
  • Genes, BRCA1 / genetics*
  • Genetic Markers
  • Haplotypes
  • Humans
  • Middle Aged
  • Mutation / genetics
  • Ovarian Neoplasms / genetics*
  • Polymerase Chain Reaction
  • Sequence Deletion / genetics

Substances

  • BRCA1 Protein
  • Codon, Terminator
  • Genetic Markers