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

Less than half of all patients with advanced-stage high-grade serous ovarian cancers (HGSC) survive more than five years post-diagnosis but those who have an exceptionally long survival could provide new 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. Transcriptomic profiling was done on 56 high grade serous ovarian cancer samples, 53 of which were primary tumors and 3 were relapse tumors. 75 samples from GSE209964 were also used as part of the cohort. **Raw data uploaded to European Genome-phenome Archive (EGA) repository under the accession codes EGAD00001000877 and EGAD00001008537**