Identifying Novel Targetable Chromosomal Alterations in Ovarian Cancer: Using Germline Copy Number Variation Association Analysis

Abstract

The heterogeneity of ovarian cancer (Ov Ca) is attributed to multiple genetic and epigenetic changes, rendering it difficult to detect the most relevant molecular alterations. Identifying copy number variations (CNVs) will be helpful in screening patients with a familial history and will ultimately facilitate early diagnosis. This work aims to determine germline CNVs that may be associated with risks for different subtypes of ovarian cancer. Using Affymetrix genome-wide human SNP 6.0 arrays, 138 germline DNA samples of non-familial ovarian cancer were analysed using Golden Helix (SVS7) software. CNVs overlapping the EYA2 (20q13.12) and WNK1 (12p13.33) genes are the top hits with a significant p-value (<0.05). Deletion is more frequent in normal and low-grade carcinomas. Commonly, ovarian cancer is copy neutral (CN2) or has copy number gains (CN3). Amplification at these locations is associated with high-grade cases, which have worse overall survival rates. A CN3 in the WNK1 gene is associated with a higher expression of mRNA. It could be concluded that ovarian cancer is associated with CN3s where the segments of DNA overlap WNK1 and EYA2. The oncogenic effect of WNK1 and EYA2 on ovaries may serve as prognostic markers for ovarian cancer.