The genomic and immune landscape of long-term survivors of high-grade serous ovarian cancer

Dale W. Garsed*, Ahwan Pandey, Sian Fereday, Catherine J. Kennedy, Kazuaki Takahashi, Kathryn Alsop, Phineas T. Hamilton, Joy Hendley, Yoke Eng Chiew, Nadia Traficante, Pamela Provan, Dinuka Ariyaratne, George Au-Yeung, Nicholas W. Bateman, Leanne Bowes, Alison Brand, Elizabeth L. Christie, Julie M. Cunningham, Michael Friedlander, Bronwyn GroutPaul Harnett, Jillian Hung, Bryan McCauley, Orla McNally, Anna M. Piskorz, Flurina A.M. Saner, Robert A. Vierkant, Chen Wang, Stacey J. Winham, Paul D.P. Pharoah, James D. Brenton, Thomas P. Conrads, George L. Maxwell, Susan J. Ramus, Celeste Leigh Pearce, Malcolm C. Pike, Brad H. Nelson, Ellen L. Goode, Anna DeFazio, David D.L. Bowtell*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

25 Scopus citations

Abstract

Fewer than half of all patients with advanced-stage high-grade serous ovarian cancers (HGSCs) survive more than five years after diagnosis, but those who have an exceptionally long survival could provide insights into tumor biology and therapeutic approaches. We analyzed 60 patients with advanced-stage HGSC who survived more than 10 years after diagnosis using whole-genome sequencing, transcriptome and methylome profiling of their primary tumor samples, comparing this data to 66 short- or moderate-term survivors. Tumors of long-term survivors were more likely to have multiple alterations in genes associated with DNA repair and more frequent somatic variants resulting in an increased predicted neoantigen load. Patients clustered into survival groups based on genomic and immune cell signatures, including three subsets of patients with BRCA1 alterations with distinctly different outcomes. Specific combinations of germline and somatic gene alterations, tumor cell phenotypes and differential immune responses appear to contribute to long-term survival in HGSC.

Original languageEnglish
Pages (from-to)1853-1864
Number of pages12
JournalNature Genetics
Volume54
Issue number12
DOIs
StatePublished - Dec 2022
Externally publishedYes

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