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Timing of whole genome duplication is associated with tumor-specific MHC-II depletion in serous ovarian cancer

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  • Nikki L. Burdett

    (Peter MacCallum Cancer Centre
    The University of Melbourne
    Eastern Health)

  • Madelynne O. Willis

    (Peter MacCallum Cancer Centre)

  • Ahwan Pandey

    (Peter MacCallum Cancer Centre)

  • Laura Twomey

    (Peter MacCallum Cancer Centre)

  • Sara Alaei

    (Peter MacCallum Cancer Centre
    Monash University)

  • David D. L. Bowtell

    (Peter MacCallum Cancer Centre
    The University of Melbourne)

  • Elizabeth L. Christie

    (Peter MacCallum Cancer Centre
    The University of Melbourne)

Abstract

Whole genome duplication is frequently observed in cancer, and its prevalence in our prior analysis of end-stage, homologous recombination deficient high grade serous ovarian cancer (almost 80% of samples) supports the notion that whole genome duplication provides a fitness advantage under the selection pressure of therapy. Here, we therefore aim to identify potential therapeutic vulnerabilities in primary high grade serous ovarian cancer with whole genome duplication by assessing differentially expressed genes and pathways in 79 samples. We observe that MHC-II expression is lowest in tumors which have acquired whole genome duplication early in tumor evolution, and further demonstrate that reduced MHC-II expression occurs in subsets of tumor cells rather than in canonical antigen-presenting cells. Early whole genome duplication is also associated with worse patient survival outcomes. Our results suggest an association between the timing of whole genome duplication, MHC-II expression and clinical outcome in high grade serous ovarian cancer that warrants further investigation for therapeutic targeting.

Suggested Citation

  • Nikki L. Burdett & Madelynne O. Willis & Ahwan Pandey & Laura Twomey & Sara Alaei & David D. L. Bowtell & Elizabeth L. Christie, 2024. "Timing of whole genome duplication is associated with tumor-specific MHC-II depletion in serous ovarian cancer," Nature Communications, Nature, vol. 15(1), pages 1-13, December.
    • Handle: RePEc:nat:natcom:v:15:y:2024:i:1:d:10.1038_s41467-024-50137-y
    DOI: 10.1038/s41467-024-50137-y
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    3. Moritz Gerstung & Clemency Jolly & Ignaty Leshchiner & Stefan C. Dentro & Santiago Gonzalez & Daniel Rosebrock & Thomas J. Mitchell & Yulia Rubanova & Pavana Anur & Kaixian Yu & Maxime Tarabichi & Ami, 2020. "The evolutionary history of 2,658 cancers," Nature, Nature, vol. 578(7793), pages 122-128, February.
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