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

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. Methylation profiling was done on 29 end stage high grade serous ovarian cancer samples. 38 primary tumours, 6 autopsy tumours and 7 fallopian tube normals from GSE65820 were also used as part of the cohort. Genome wide DNA methylation profiling of 29 tumours of end stage high grade serous ovarian cancer. The Illumina Infinium MethylationEPIC BeadChip was used to obtain DNA methylation profiles across approximately 850,000 CpGs. 38 primary tumours, 6 autopsy tumours and 7 fallopian tube normals from GSE65820 were also used as part of the cohort.