Although more than 100 different BRCA1 germ-line mutations have alread
y been identified in breast and/or ovarian cancer families, we report
for the first time a deleterious genomic rearrangement in BRCA1. A 1-k
b deletion comprising exon 17 was found in a large breast and ovarian
cancer family, leading to a frameshift in the mutant mRNA due to the a
bsence of exon 17. This deletion is probably the result of a recombina
tion between two closely related Alu sequences. It mas not detected by
conventional PCR-based methods involving the genomic screening of the
22 coding exons or reverse transcription-PCR because the transcript w
ithout exon 17 is unstable in lymphoblastoid cell lines. Therefore, re
arrangements in the BRCA1 gene should be sought in breast/ovarian canc
er families in which no mutations have been found by PCR-based methods
in the coding region or in the splice sites.