Multi-omic analysis of homologous recombination deficient, end-stage ovarian cancer [Expression]

High grade serous ovarian cancer (HGSC) is frequently characterized by homologous recombination (HR) DNA repair deficiency, and while most such tumors are sensitive to initial treatment, acquired resistance is common. We undertook a multi-omics approach to interrogate the molecular diversity in end-stage disease, using multiple autopsy samples collected from 15 women with HR-deficient HGSC. Patients had polyclonal disease, and several resistance mechanisms were identified within most patients, including reversion mutations and HR restoration by other means. We also observed frequent whole genome duplication, and global changes in immune composition with evidence of immune escape. This analysis highlights diverse evolutionary changes within HGSC that conspire to evade therapy and ultimately overwhelm individual patients. Transcriptomic profiling was done on 45 end stage high grade serous ovarian cancer samples, 41 of which were autopsy tumors, 3 primary tumors and 1 ascites sample. 38 primary samples and 6 autopsy samples from GSE209964 were also used as part of the cohort. NOTE: the raw FASTQ files are still being uplaoded to EGA so we will update the GEO submission later once we have the study ID for the raw data