Journal
NATURE GENETICS
Volume 54, Issue 12, Pages -Publisher
NATURE PORTFOLIO
DOI: 10.1038/s41588-022-01230-9
Keywords
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Categories
Funding
- U.S. Army Medical Research and Materiel Command Ovarian Cancer Research Program [W81XWH-16-2-0010, W81XWH-21-1-0401]
- National Health and Medical Research Council of Australia [1092856, 1117044, 2008781, 1186505]
- U.S. National Cancer Institute [P30CA046592, P30CA008748]
- Border Ovarian Cancer Awareness Group
- Garvan Research Foundation
- Graf Family Foundation
- Mrs Margaret Rose AM, Arthur Coombs and family
- Piers K Fowler Fund
- U.S. Army Medical Research and Materiel Command [DAMD17-01-1-0729]
- Cancer Council Victoria
- Cancer Council New South Wales
- Cancer Council South Australia
- Cancer Council Tasmania
- Cancer Foundation of Western Australia
- Ovarian Cancer Australia
- Peter MacCallum Cancer Foundation
- Cancer Institute NSW [12/RIG/117, 15/RIG/1-16]
- Department of Gynaecological Oncology, Westmead Hospital
- Sydney West Translational Cancer Research Centre - Cancer Institute NSW [15/TRC/1-01]
- Swiss National Foundation [P2BEP3-172246]
- Swiss Cancer Research Foundation [BIL KFS-3942-08-2016]
- Uniscientia Foundation
- Cancer Research UK [A22905]
- BC Cancer Foundation
- Canada's Networks of Centres of Excellence (BioCanRx)
- Genome BC
- Canada Foundation for Innovation
- U.S. National Cancer Institute U54 program [U54CA209978]
- Queensland Cancer Fund
- National Health and Medical Research Council of Australia (NHMRC) [ID199600, ID400413, ID400281]
- NHMRC [ID310670, ID628903, APP1161198]
- Swiss National Science Foundation (SNF) [P2BEP3_172246] Funding Source: Swiss National Science Foundation (SNF)
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This study analyzed the genomic, transcriptomic, and methylomic profiles of patients with advanced-stage HGSC who survived more than 10 years after diagnosis. Long-term survivors had more alterations in DNA repair genes and higher neoantigen load. Patients were clustered into survival groups based on genomic and immune cell signatures, including different subsets of patients with BRCA1 alterations. Specific combinations of genetic and immune factors contribute to long-term survival in HGSC.
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.
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