Characterization of Mutational Status, Spheroid Formation, and Drug Response of a New Genomically-Stable Human Ovarian Clear Cell Carcinoma Cell Line, 105C

Abstract

Ovarian clear cell carcinoma (OCCC) is a rare subtype of gynecological cancer for which well-characterized and authenticated model systems are scarce. We provide an extensive characterization of ‘105C’, a cell line generated from an adenocarcinoma of the clear cell histotype using targeted next-generation sequencing, cytogenetic microarrays, along with analyses of AKT/mTOR signaling. We report that that the 105C cell line is a bona fide OCCC cell line, carrying PIK3CA, PTEN, and ARID1A gene mutations, consistent with OCCC, yet maintain a stable genome as reflected by low copy number variation. Unlike KOC-7c, TOV-21G, and RMG-V OCCC lines also mutated for the above genes, the 105C cells do not carry mutations in mismatch repair genes. Importantly, we show that 105C cells exhibit greater resistance to mTOR inhibition and carboplatin treatment compared to 9 other OCCC cell lines in 3D spheroid cultures. This resistance may be attributed to 105C cells remaining dormant in suspension culture which surprisingly, contrasts with several other OCCC lines which continue to proliferate in long-term suspension culture. 105C cells survive xenotransplantation but do not proliferate and metastasize. Collectively, we show that the 105C OCCC cell line exhibits unique properties useful for the pre-clinical investigation of OCCC pathobiology.