Characterization of RNF144B and PPP2R2A identified by a novel approach using TCGA data in ovarian cancer.

Abstract

TCGA has identified predominant somatic copy number alterations (SCNA) affecting numerous genes in HGSOC. To identify cancer-driver genes from the regions of SCNA, we have devised a scoring system that integrates information from different genetic alterations. Applying this scoring system to the TCGA-HGSOC dataset (n = 316) we have identified several well-known and novel putative cancer genes in HGSOC. We functionally validated the roles of two previously unknown genes, RNF144B and PPP2R2A. RNF144B, an E3 ubiquitin-ligase is amplified and overexpressed in 16% of HGSOC (TCGA). Overexpression of RNF144B in ovarian cancer cells increased cell proliferation, colony formation, and migration. RNF144B was significantly overexpressed in 50% of primary tumors from patients with HGSOC compared to the ovary. Further, it had significantly reduced expression in tumors after chemotherapy. PPP2R2A, the regulatory subunit of PP2A is deleted and downregulated in 38% of HGSOCs (TCGA). Overexpression of PPP2R2A inhibited cell proliferation, colony-formation, migration, and invasion in ovarian cancer cells. In OVCAR-5, which expresses low levels of PPP2R2A, Niraparib inhibited cell proliferation. PPP2R2A was not expressed in 72% of HGSOCs. This report demonstrates this approach to identifying genes from the TCGA data. Further experiments are required to conclusively prove the role of these genes in the pathogenesis of ovarian cancer.