Genomic structure of chromosome 17 deletions in BRCA1-associated ovarian cancers

The aim of this study was to determine the genomic structure of the deletions on chromosome 17 in ovarian carcinomas from women with inherited BRCA1 mutations. Normal and tumor DNA from 14 ovarian tumors associated with inherited BRCA1 mutations were extracted and tested for loss of heterozygosity (LOH) at microsatellite markers along chromosome 17. Finer mapping using more microsatellite markers and single nucleotide polymorphisms helped further define the LOH margins. The genomic repeated elements within the LOH breakpoint regions were identified using the University of California Santa Cruz Genome Database, and the frequencies were compared to regions of equal GC percentages across the genome. Of the 14 ovarian tumors, 12 showed LOH of the entire chromosome 17. The other two tumors lost the distal end of the 17q arm. The breakpoints of these two tumors occurred in regions with significantly high frequencies of short interspersed nuclear elements (SINE), specifically Alu elements. Ovarian tumors of high grade and stage have large regions of LOH along chromosome 17, with most tumors showing loss of the entire chromosome. In those tumors with retention of part of chromosome 17, LOH margins suggest that a high Alu content may have a role in the deletions.