Germline copy number variations in BRCA1-associated ovarian cancer patients

We investigated characteristics of germline copy number variations (CNV) in BRCA1‐associated ovarian cancer patients by comparing them to CNVs present in sporadic ovarian cancer patients. Germline CNVs in 51 BRCA1‐associated, 33 sporadic ovarian cancer patients, and 47 healthy women were analyzed by both signal intensity and genotyping data using the Affymetrix Genome‐Wide Human SNP Array 6.0. The total number of CNVs per genome was greater in the sporadic group (median 26, range 12–34) than in the BRCA1 group (median 21, range 11–35; post hoc P < 0.05) or normal group (median 20, range 7–32; post hoc P < 0.05). While the number of amplifications per genome was higher in the sporadic group (median 13, range 7–26) than in the BRCA1 group (median 8, range 3–23; post hoc P < 0.001), the number of deletions per genome was higher in the BRCA1 group (median 12, range 6–24) than in the sporadic group (median 9, range 3–17; post hoc P < 0.01). In addition, 31 previously unknown CNV regions were present specifically in the BRCA1 group. When we performed pathway analysis on the 241 overlapping genes mapped to these novel CNV regions, the ‘purine metabolism’ and ‘14‐3‐3‐mediated signaling’ pathways were over‐represented (Fisher's exact test, P < 0.01). Our study shows that there are qualitative differences in genomic CNV profiles between BRCA1‐associated and sporadic ovarian cancer patients. Further studies are necessary to clarify the significance of the genomic CNV profile unique to BRCA1‐associated ovarian cancer patients. © 2010 Wiley‐Liss, Inc.