Genomic landscape of ovarian clear cell carcinoma via whole exome sequencing
Introduction
Ovarian cancer, the most lethal gynecologic malignancy, imposes a global burden in both developed and developing countries [1]. In Korea, the incidence of ovarian cancer has been gradually increasing and is expected to reach 2.5% (2,618) of new cancer cases and 3.8% (1,168) of all cancer deaths among women in 2017 [2], [3]. Of the histologic types, the majority (90%) of ovarian cancers are epithelial ovarian cancers (EOCs), which are further grouped into different histologic subtypes [4].
Ovarian clear cell carcinoma (OCCC), a subtype of EOC, is known to be less sensitive to chemotherapy and has a poorer prognosis than other histologic EOC subtypes, such as serous or endometrioid adenocarcinomas [5]. OCCC is associated with endometriosis (EMS), which is a common benign condition in reproductive-age women [6], [7]. Interestingly, OCCC is more common in East Asian women than in Western women: it accounts for 24% of EOCs in Japan but only a small portion of EOCs in Western countries [8]. In Korea, OCCC is the fourth most common histologic subtype, which accounts for 10.3% of EOCs, and the incidence of OCCC has increased markedly across all age groups since 1999 [9].
In accordance with the era of precision medicine, it is obvious that reliable genetic diagnosis is essential for providing individualized treatment for patients with OCCC. In OCCC, both a clinical approach, considering the presence of underlying EMS, and a genomic approach, such as those conducted by The Cancer Genome Analysis (TCGA) Group, may be necessary [10]. However, the low incidence of OCCC hinders such integrative genomic analyses. To date, only small genomic studies of OCCC have been reported from some East Asian countries; the genomic landscape of Korean OCCC has not yet been investigated.
The aim of this study was to obtain whole exome sequencing (WES) data of Korean OCCC via the next generation sequencing (NGS) technique. Genomic profiles were compared between EMS-associated OCCC (EMS-OCCC) and Non-EMS-OCCC.
Section snippets
Materials and methods
This retrospective case-control study, using genomic analyses, was conducted after obtaining approval from the Institutional Review Board of Seoul National University Hospital (IRB No. 1609-081-792).
Characteristics of 15 Korean patients with OCCC
The patients' clinicopathologic characteristics are depicted in Table 1. Their median age was 51.1 years. The numbers of patients with stage I, II, and III disease were 9, 2, and 4, respectively. All patients underwent PDS, which was followed by adjuvant chemotherapy in all except two patients. During the median observation period of 23.4 months, two patients had a recurrence and received second-line chemotherapy. Of these, one patient eventually died despite treatment at 19.0 months after
Discussion
In the present study, we successfully characterized the genomic landscape of 15 Korean patients with OCCC. This cancer featured complex genomic alterations. To our knowledge, this is the first report of an NGS WES study in Korean patients with OCCC, as well as the first attempt to compare genomic profiles of OCCC according to the presence or absence of EMS. As TCGA Research Network emphasizes, genomic analyses and identification of alterations will provide new therapeutic approaches and allow
Conflict of interest
No conflicts of interest, relevant to this manuscript, exist.
Ackwnowledgments
This work was supported by a grant from the Seoul National University Hospital Research Fund (Grant No. 04-2016-0310). The biospecimens for this study were provided by the Seoul National University Hospital Human Biobank, a member of the National Biobank of Korea, which is supported by the Ministry of Health and Welfare. All samples, derived from the National Biobank of Korea, were obtained with informed consent under institutional review board-approved protocols.
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These two authors contributed equally as first authors.