Timing of whole genome duplication is associated with tumor-specific MHC-II depletion in serous ovarian cancer
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期刊论文
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出版模式：
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发表日期：
2024年7月18日
- Nikki L. Burdett,
- Madelynne O. Willis,
- Ahwan Pandey,
- Laura Twomey,
- Sara 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,
- Y. E. Chiew,
- A. Stenlake,
- H. Sullivan,
- A. Mellon,
- R. Robertson,
- T. Vanden 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,
- N. Burdett,
- 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,
- M. K. Oehler,
- C. Hall,
- T. Dodd,
- P. Blomfield,
- D. Challis,
- R. McIntosh,
- A. Parker,
- D. Healy,
- T. Jobling,
- T. Manolitsas,
- J. McNealage,
- P. Rogers,
- B. Susil,
- E. Sumithran,
- I. Simpson,
- N. Zeps,
- I. Hammond,
- Y. Leung,
- A. McCartney,
- R. Stuart-Harris,
- F. Kirsten,
- J. Rutovitz,
- P. Clingan,
- J. Shannon,
- T. Bonaventura,
- J. Stewart,
- S. Begbie,
- A. Glasgow,
- M. Friedlander,
- M. Links,
- J. Grygiel,
- J. Hill,
- A. Brand,
- K. Byth,
- P. Harnett,
- G. Wain,
- R. Jaworski,
- R. Sharma,
- B. Ward,
- D. Papadimos,
- A. Crandon,
- M. Cummings,
- K. Horwood,
- A. Obermair,
- L. Perrin,
- D. Wyld,
- J. Nicklin,
- T. Healy,
- K. Pittman,
- D. Henderson,
- J. Miller,
- J. Pierdes,
- B. Brown,
- R. Rome,
- D. Allen,
- P. Grant,
- S. Hyde,
- R. Laurie,
- M. Robbie,
- P. Waring,
- V. Billson,
- J. Pyman,
- D. Neesham,
- M. Quinn,
- C. Underhill,
- R. Bell,
- L. F. Ng,
- R. Blum,
- V. Ganju,
- M. Buck,
- I. Haviv,
- David D. L. Bowtell,
- Elizabeth L. Christie
摘要
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.