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Genomic and transcriptomic analysis of high-grade serous ovarian carcinoma
( Se Ik Kim ) , ( Aeran Seol ) , ( Maria Lee ) , ( Hee Seung Kim ) , ( Hyun Hoon Chung ) , ( Jae-weon Kim ) , ( Noh Hyun Park ) , ( Yong-sang Song )
UCI I410-ECN-0102-2019-500-001581424
This article is 4 pages or less.

Objective: High-grade serous ovarian carcinoma (HGSOC) is one of the deadliest female malignancies with worse survival outcome. We aimed to broaden genomic understanding of HGOC, and to aid the development of targeted therapies and prognostic markers for HGOC via next generation sequencing technology. Methods: We used serum samples and cancer tissues, stored at the Seoul National University Hospital Human Biobank, that were collected from women diagnosed with HGSOC between 2013 and 2016. In total, 20 patients were enrolled. To enable comprehensive profiling, we performed whole exome sequencing and whole transcriptome sequencing on fresh frozen cancers via the technique of next generation sequencing. Results: We discovered that HGOC is characterized by MUC4 mutations (85%) and TP53 mutations (50%) in almost all tumors. Despite their low prevalence, repeatedly altered genes observed in HGSOC were ERG, ATR, NOTCH4, CSMD3 and KEAP1. We also identified somatic copy number gain on the region of BCL6, PIK3CA, TP63, SOX2 and MYC, and somatic copy number loss on the region of APC, CHEK1 and ATM. To discover candidates for prognostic biomarkers, we conducted differential gene expression analyses. In the poorer survival group, we found increased expression of HOXA9 and HOXA10, the members of homeobox (HOX) gene family, and increased expression of FGFBP1, PDGFRB, F3, BCL2L1 and MAP2K5, which were known to be associated with cell proliferation and survival pathway. In addition, through the analyses of differential splicing, alternative splicing of EME1 was identified as a poor prognostic marker for HGSOC. Conclusion: We successfully obtained genomic and transcriptomic landscape of 20 patients with HGSOC, and discovered therapeutic target genes, as well as prognostic biomarkers.

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