A deletion/insertion mutation in the BRCA2 gene in a breast cancer family:A possible role of the Alu-polyA tail in the evolution of the deletion

Patients with breast and/or ovarian cancer were screened for gross rearrang ements in the BRCA2 gene by Southern hybridization, with exon 10 and a frag ment of exon 11 used as probes. One breast cancer patient with a positive f amily history had a 6.2-kb deletion including exons 12 and 13. The deletion breakpoint in intron 11 was in the 3' polyA tail of an Alu element, where a track of approximate to 60 adenine nucleotide residues was inserted. Expa nsion of the Alu-polyA tail may have resulted from polymerase slippage duri ng replication, representing a novel mechanism in which Alu elements mediat e deletion/insertion mutations. (C) 2001 Wiley-Liss, Inc.