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

NL Burdett; MO Willis; A Pandey; L Twomey; S Alaei; D Bowtell; G Chenevix-Trench; A Green; P Webb; A DeFazio; D Gertig; N Traficante; S Fereday; S Moore; J Hung; K Harrap; T Sadkowsky; N Pandeya; L Bowes; L Galletta; D Giles; J Hendley; K Alsop; B Alexander; P Ashover; S Brown; T Corrish; L Green; L Jackman; K Ferguson; K Martin; A Martyn; B Ranieri; M Malt; YE Chiew; A Stenlake; H Sullivan; A Mellon; R Robertson; TV Bergh; M Jones; P Mackenzie; J Maidens; K Nattress; J White; V Jayde; P Mamers; T Schmidt; H Shirley; S Viduka; H Tran; S Bilic; L Glavinas; C Ball; C Young; J Brooks; L Mileshkin; G Au-Yeung; K Phillips; D Rischin; R Delahunty; E Christie; D Garsed; S Fox; D Johnson; S Lade; M Loughrey; N O’Callaghan; W Murray; D Purdie; D Whiteman; A Proietto; S Braye; G Otton; C Camaris; R Crouch; L Edwards; N Hacker; D Marsden; G Robertson; D Bell; S Baron-Hay; A Ferrier; G Gard; D Nevell; N Pavlakis; S Valmadre; B Young; P Beale; J Beith; J Carter; C Dalrymple; R Houghton; P Russell; M Davy; MK Oehler; C Hall; T Dodd; P Blomfield

Journal article

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

NL Burdett, MO Willis, A Pandey, L Twomey, S Alaei, D Bowtell, G Chenevix-Trench, A Green, P Webb, A DeFazio, D Gertig, N Traficante, S Fereday, S Moore, J Hung, K Harrap, T Sadkowsky, N Pandeya, L Bowes, L Galletta Show all

Nature Communications | NATURE PORTFOLIO | Published : 2024

DOI: 10.1038/s41467-024-50137-y

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 r..

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University of Melbourne Researchers

Nikki Burdett Author

David Bowtell Author

Dorota Gertig Author

Nadia Traficante Author

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Grants

Awarded by Cancer Council Victoria

Funding Acknowledgements

We acknowledge the statistical input of Madawa Jayawardana with regard to complex model fitting. We thank Peter MacCallum Cancer Centre Molecular Genomics Core facility, supported by the Australian Cancer Research Foundation. The Australian Ovarian Cancer Study (AOCS) acknowledges the cooperation of the participating institutions in Australia and acknowledges the contribution of the study nurses, research assistants and all clinical and scientific collaborators to the study. The complete AOCS Study Group can be found atwww.aocstudy.org. We would like to thank all of the women who participated in these research programs. This research was financially supported by grants from Department of Health and Human Services through the National Health and Medical Research Council of Australia (NHMRC, APP1189939 to N.L.B., APP1161198 to D.D.L.B. and E.L.C.) and the Victorian Cancer Agency (VCAMCRF21004 to E.L.C.). The AOCS Group was supported by the U.S. Army Medical Research and Materiel Command under DAMD17-01-1-0729, The Cancer Council Victoria, Queensland Cancer Fund, The Cancer Council New South Wales, The Cancer Council South Australia, The Cancer Council Tasmania and The Cancer Foundation of Western Australia (Multi-State Applications 191, 211 and 182) and NHMRC (ID199600; ID400413 and ID400281). The Australian Ovarian Cancer Study gratefully acknowledges additional support from Ovarian Cancer Australia and the Peter MacCallum Cancer Foundation. Figure 1a was created with BioRender.com released under a Creative Commons Attribution-NonCommercial-NoDerivs 4.0 International license.