A 1-KB ALU-MEDIATED GERM-LINE DELETION REMOVING BRCA1 EXON-17

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.