[Mutation by deletion-insertion in BRCA-1 gene in three unrelated French breast/ovarian cancer families: possible implication of a mobile element]

Abstract

A new type of mutation by deletion-insertion in BRCA-1 gene is found in three unrelated French breast/ovarian cancer families. Surprisingly, deletion and insertion occurred at the same nucleotide position at the end of exon 11 (3958del5ins4), thus generating a truncated protein. This original mutation consists in a deletion of 5 bp (CTCAG) and in an insertion of 4 different bp (AGGC). Here, we proposed two hypothesis to explain this phenomenom. The first hypothesis is the formation of a hairpin stem-loop structure comprising the mutational site and the sequence corresponding to the duplication insertion 2 nucleotides before the mutation. The second hypothesis, more speculative, consists in an abortive integration of a human mobile element as a human transposon (tigger 1) which involved a deletion of 5 bp during its excision and an insertion of 4 bases corresponding to the 5' extremity of the transposon.