Germline copy number variations in BRCA1‐associated ovarian cancer patients

Abstract

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.

Classification of cancers based on copy number variation landscapes

“…Its amplifications of CNVs have been reported in many cancer patients, such as BRCA and OV [27]. Research has found that this gene is activated in various tumors, such as colon cancers [28] and esophageal cancers.…”

Germline DNA copy number variations as potential prognostic markers for non-muscle invasive bladder cancer progression

“…Previous reports demonstrated the association between CNVs and the risk of several human malignancies (11)(12)(13)(14)(15)(16). PCSK6 is a member of the protease family of proprotein convertases, which activate precursor proteins by cleaving at the specific recognition sequence RXK/RR (20).…”

“…Recent studies have described germline CNVs as potential susceptibility loci for a range of diseases, including infectious, autoimmune and neuropsychiatric diseases (7)(8)(9)(10). Concerning malignancies, CNVs have recently been reported as markers predisposing individuals to neuroblastoma, prostate cancer, pancreatic cancer, colorectal cancer, ovarian cancer and breast cancer risk (11)(12)(13)(14)(15)(16). However, the significance of CNVs in NMIBC remains unclear.…”

Germline DNA Variations in Breast Cancer Predisposition and Prognosis: A Systematic Review of the Literature

“…Even though the study reported lack of associations of common CNVs with complex diseases, perhaps due to a limited number of common CNVs considered in the analysis, the study certainly opened possibilities for a more systematic and comprehensive analysis (larger coverage) of germline CNVs as predisposition factors for complex diseases. Another study that evaluated germline CNV profiles between BRCA1 -associated and sporadic ovarian cancer patients reported substantial differences in copy number gains and losses between these 2 groups of cancer patients [Yoshihara et al, 2011]. Germline CNVs were also reported to be associated with susceptibility to familial pancreatic and breast cancers [Al-Sukhni et al, 2012].…”