The Cancer Genome Atlas (TCGA) project has conducted comprehensive genomic and epigenomic analyses of 489 high-grade serous ovarian adenocarcinomas (HGS-OvCa) to identify molecular abnormalities that influence pathophysiology and affect patient outcomes. Key findings include: 1. **Molecular Aberrations**: High-grade serous ovarian cancer is characterized by *TP53* mutations in almost all tumors (96%), recurrent somatic mutations in nine other genes including *NF1*, *BRCA1*, *BRCA2*, *RBI*, and *CDK12*, 113 significant focal DNA copy number aberrations, and promoter methylation events involving 168 genes. 2. **Transcriptional and MicroRNA Subtypes**: Four transcriptional subtypes, three microRNA subtypes, and four promoter methylation subtypes were identified, providing new insights into the molecular heterogeneity of HGS-OvCa. 3. **Survival and Pathways**: A 193-gene transcriptional signature was identified that predicts overall survival. Pathway analyses suggested that homologous recombination is defective in about half of the tumors analyzed, and that NOTCH and FOXM1 signaling are involved in serous ovarian cancer pathophysiology. 4. **Therapeutic Implications**: The study identified potential therapeutic targets, including PARP inhibitors for tumors with homologous recombination defects, and inhibitors for genes in regions of recurrent amplification. 5. **Clinical Impact**: The findings provide a comprehensive view of the molecular landscape of HGS-OvCa, which can inform the development of more effective treatments and improve patient outcomes. This integrated genomic analysis of HGS-OvCa offers a critical resource for advancing the understanding and treatment of this deadly disease.The Cancer Genome Atlas (TCGA) project has conducted comprehensive genomic and epigenomic analyses of 489 high-grade serous ovarian adenocarcinomas (HGS-OvCa) to identify molecular abnormalities that influence pathophysiology and affect patient outcomes. Key findings include: 1. **Molecular Aberrations**: High-grade serous ovarian cancer is characterized by *TP53* mutations in almost all tumors (96%), recurrent somatic mutations in nine other genes including *NF1*, *BRCA1*, *BRCA2*, *RBI*, and *CDK12*, 113 significant focal DNA copy number aberrations, and promoter methylation events involving 168 genes. 2. **Transcriptional and MicroRNA Subtypes**: Four transcriptional subtypes, three microRNA subtypes, and four promoter methylation subtypes were identified, providing new insights into the molecular heterogeneity of HGS-OvCa. 3. **Survival and Pathways**: A 193-gene transcriptional signature was identified that predicts overall survival. Pathway analyses suggested that homologous recombination is defective in about half of the tumors analyzed, and that NOTCH and FOXM1 signaling are involved in serous ovarian cancer pathophysiology. 4. **Therapeutic Implications**: The study identified potential therapeutic targets, including PARP inhibitors for tumors with homologous recombination defects, and inhibitors for genes in regions of recurrent amplification. 5. **Clinical Impact**: The findings provide a comprehensive view of the molecular landscape of HGS-OvCa, which can inform the development of more effective treatments and improve patient outcomes. This integrated genomic analysis of HGS-OvCa offers a critical resource for advancing the understanding and treatment of this deadly disease.