Targeted sequencing of a specific gene panel detects a high frequency of ARID1A and PIK3CA mutations in ovarian clear cell carcinoma

Abstract

Background: The objective of this study was to assess the mutational profile in epithelial ovarian cancer using formalin-fixed, paraffin-embedded (FFPE) tumor specimens from a Taiwanese population by performing targeted sequencing of 9 cancer-associated genes. Methods: Targeted sequencing was performed on 32 formalin-fixed, paraffin embedded (FFPE) tumor specimens, consisting of matched samples from 16 epithelial ovarian cancer patients. Genetic alterations in the 9 cancer-associated genes were detected using a deep sequencing (>1000×) approach. Results: ARID1A and PIK3CA were the most frequently mutated genes. Specifically, ARID1A mutations and PIK3CA mutations were detected in 77.8% and 66.7% of ovarian clear cell carcinoma patients, respectively. Mutations in other genes, including MLH1 (6.3%) and CREBBP (6.3%), were detected in the Taiwanese population. We also identified coexisting ARID1A-PIK3CA mutations (43.8%) and ARID1A-KRAS mutations (12.5%) in tumors. It should also be noted that we identified the presence of three coexisting mutations, the ARID1A-KRAS-PIK3CA mutations and the ARID1A-CREBBP-PIK3CA mutations. Conclusions: In summary, we identified novel genetic alterations in patients with epithelial ovarian carcinoma (EOC) in a Taiwanese populations. Further studies are needed to elucidate the mechanism of chromatin remodeling to examine the role of the PI3K/AKT pathway, to determine the critical roles of these mechanisms in tumor development and the progression of ovarian malignancy and to investigate new targeted therapies. Overall, our findings were reliable and are worthy of further study.