Whole-genome sequencing revealed novel prognostic biomarkers and promising targets for therapy of ovarian clear cell carcinoma

Hiroaki Itamochi, Tetsuro Oishi, Nao Oumi, Satoshi Takeuchi, Kosuke Yoshihara, Mikio Mikami, Nobuo Yaegashi, Yasuhisa Terao, Kazuhiro Takehara, Kimio Ushijima, Hidemichi Watari, Daisuke Aoki, Tadashi Kimura, Toshiaki Nakamura, Yoshihito Yokoyama, Junzo Kigawa, Toru Sugiyama

Research output: Contribution to journalArticle

15 Citations (Scopus)

Abstract

Background:Ovarian clear cell carcinoma (OCCC) is mostly resistant to standard chemotherapy that results in poor patient survival. To understand the genetic background of these tumours, we performed whole-genome sequencing of OCCC tumours.Methods:Tumour tissue samples and matched blood samples were obtained from 55 Japanese women diagnosed with OCCC. Whole-genome sequencing was performed using the Illumina HiSeq platform according to standard protocols.Results:Alterations to the switch/sucrose non-fermentable (SWI/SNF) subunit, the phosphatidylinositol-3-kinase (PI3K)/Akt signalling pathway, and the receptor tyrosine kinase (RTK)/Ras signalling pathway were found in 51%, 42%, and 29% of OCCC tumours, respectively. The 3-year overall survival (OS) rate for patients with an activated PI3K/Akt signalling pathway was significantly higher than that for those with inactive pathway (91 vs 40%, hazard ratio 0.24 (95% confidence interval (CI) 0.10-0.56), P=0.0010). Similarly, the OS was significantly higher in patients with the activated RTK/Ras signalling pathway than in those with the inactive pathway (91 vs 53%, hazard ratio 0.35 (95% CI 0.13-0.94), P=0.0373). Multivariable analysis revealed that activation of the PI3K/Akt and RTK/Ras signalling pathways was an independent prognostic factor for patients with OCCC.Conclusions:The PI3K/Akt and RTK/Ras signalling pathways may be potential prognostic biomarkers for OCCC patients. Furthermore, our whole-genome sequencing data highlight important pathways for molecular and biological characterisations and potential therapeutic targeting in OCCC.

Original languageEnglish
Pages (from-to)717-724
Number of pages8
JournalBritish Journal of Cancer
Volume117
Issue number5
DOIs
Publication statusPublished - 2017 Aug 22

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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    Itamochi, H., Oishi, T., Oumi, N., Takeuchi, S., Yoshihara, K., Mikami, M., Yaegashi, N., Terao, Y., Takehara, K., Ushijima, K., Watari, H., Aoki, D., Kimura, T., Nakamura, T., Yokoyama, Y., Kigawa, J., & Sugiyama, T. (2017). Whole-genome sequencing revealed novel prognostic biomarkers and promising targets for therapy of ovarian clear cell carcinoma. British Journal of Cancer, 117(5), 717-724. https://doi.org/10.1038/bjc.2017.228