Identification of somatic genetic alterations in ovarian clear cell carcinoma with next generation sequencing

• DOI: 10.1002/gcc.22507
• Publication Date: 2017-10-17T02:56:41Z
• Authors: Yusuke Shibuya; Hideki Tokunaga; Sakae Saito; Kazurou Shimokawa; Fumiki Katsuoka; Li Bin; Kaname Kojima; Masao Nagasaki; Masayuki Yamamoto; Nobuo Yaegashi; Jun Yasuda
• Keywords: Identification

Abstract Ovarian clear cell carcinoma (OCCC) is the most refractory subtype of ovarian cancer and more prevalent in Japanese than Caucasians (25% 5% all cancer, respectively). The aim this study to discover genomic alterations that may cause OCCC effective molecular targets for chemotherapy. Paired DNAs 48 tissues corresponding noncancerous were extracted from formalin‐fixed, paraffin embedded specimens collected between 2007 2015 at Tohoku University Hospital. All underwent exome sequencing somatic genetic identified. We divided cases into three clusters based on mutation spectra. Clinical characteristics such as age onset endometriosis are similar among but one cluster shows mutations related APOBEC activation, indicating its contribution subset cases. There hypermutated (showing 12‐fold or higher other 45 cases) they have germline mismatch repair gene alterations. frequently mutated genes ARID1A (66.7%), PIK3CA (50%), PPP2R1A (18.8%), KRAS (16.7%). Somatic important selection chemotherapeutic agents, BRAF , ERBB2 PDGFRB PGR, found 27.1% cases, clinical importance analysis OCCC. Our suggests instability caused by either defect activation play critical roles carcinogenesis.