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Molecular stratification of endometrioid ovarian carcinoma predicts clinical outcome

Author

Listed:
  • Robert L. Hollis

    (University of Edinburgh)

  • John P. Thomson

    (University of Edinburgh)

  • Barbara Stanley

    (University of Edinburgh)

  • Michael Churchman

    (University of Edinburgh)

  • Alison M. Meynert

    (University of Edinburgh)

  • Tzyvia Rye

    (University of Edinburgh)

  • Clare Bartos

    (University of Edinburgh)

  • Yasushi Iida

    (University of Edinburgh
    The Jikei University School of Medicine)

  • Ian Croy

    (University of Edinburgh)

  • Melanie Mackean

    (Western General Hospital)

  • Fiona Nussey

    (Western General Hospital)

  • Aikou Okamoto

    (The Jikei University School of Medicine)

  • Colin A. Semple

    (University of Edinburgh)

  • Charlie Gourley

    (University of Edinburgh)

  • C. Simon Herrington

    (University of Edinburgh)

Abstract

Endometrioid ovarian carcinoma (EnOC) demonstrates substantial clinical and molecular heterogeneity. Here, we report whole exome sequencing of 112 EnOC cases following rigorous pathological assessment. We detect a high frequency of mutation in CTNNB1 (43%), PIK3CA (43%), ARID1A (36%), PTEN (29%), KRAS (26%), TP53 (26%) and SOX8 (19%), a recurrently-mutated gene previously unreported in EnOC. POLE and mismatch repair protein-encoding genes were mutated at lower frequency (6%, 18%) with significant co-occurrence. A molecular taxonomy is constructed, identifying clinically distinct EnOC subtypes: cases with TP53 mutation demonstrate greater genomic complexity, are commonly FIGO stage III/IV at diagnosis (48%), are frequently incompletely debulked (44%) and demonstrate inferior survival; conversely, cases with CTNNB1 mutation, which is mutually exclusive with TP53 mutation, demonstrate low genomic complexity and excellent clinical outcome, and are predominantly stage I/II at diagnosis (89%) and completely resected (87%). Moreover, we identify the WNT, MAPK/RAS and PI3K pathways as good candidate targets for molecular therapeutics in EnOC.

Suggested Citation

  • Robert L. Hollis & John P. Thomson & Barbara Stanley & Michael Churchman & Alison M. Meynert & Tzyvia Rye & Clare Bartos & Yasushi Iida & Ian Croy & Melanie Mackean & Fiona Nussey & Aikou Okamoto & Co, 2020. "Molecular stratification of endometrioid ovarian carcinoma predicts clinical outcome," Nature Communications, Nature, vol. 11(1), pages 1-10, December.
    • Handle: RePEc:nat:natcom:v:11:y:2020:i:1:d:10.1038_s41467-020-18819-5
    DOI: 10.1038/s41467-020-18819-5
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