The Cancer Genome Atlas (TCGA) project analyzed 489 high-grade serous ovarian adenocarcinomas (HGS-OvCa) and 316 of these tumors for exome sequencing, revealing that TP53 mutations are present in nearly all cases (96%), while nine other genes show low but recurrent somatic mutations. The study identified 113 significant focal DNA copy number aberrations and promoter methylation events in 168 genes. Four transcriptional subtypes, three microRNA subtypes, four promoter methylation subtypes, and a survival-associated transcriptional signature were identified. Pathway analyses indicated that homologous recombination is defective in about half of the tumors, and NOTCH and FOXM1 signaling are involved in the pathophysiology of serous ovarian cancer. Ovarian cancer is the fifth leading cause of cancer death among women in the US, with 21,880 new cases and 13,850 deaths estimated in 2010. Most deaths are due to advanced-stage, high-grade serous ovarian cancer. Standard treatment includes aggressive surgery followed by platinum-taxane chemotherapy, but recurrence occurs in about 25% of patients within six months. The five-year survival rate is 31%. Approximately 13% of HGS-OvCa cases are due to germline mutations in BRCA1/2, while the majority are due to somatic aberrations. The TCGA researchers conducted comprehensive genomic and epigenomic analyses to identify molecular abnormalities influencing pathophysiology and treatment. Microarray analyses provided high-resolution measurements of mRNA, miRNA, DNA copy number, and DNA promoter methylation for 489 HGS-OvCa tumors. Massively parallel sequencing provided whole-exome DNA sequence information for 316 samples. The study identified 19,356 somatic mutations, with TP53 mutated in 303 of 316 samples. BRCA1 and BRCA2 had germline mutations in 9% and 8% of cases, respectively. Six other genes were found to be statistically recurrently mutated. The study also identified 50 focal deletions and 63 focal amplifications, with several genes involved in key pathways such as RB1, PI3K/RAS, and FOXM1. The study identified four transcriptional subtypes of HGS-OvCa, with survival duration differing significantly between subtypes. A 193-gene transcriptional signature was defined to predict overall survival. The study also identified three miRNA subtypes, with survival duration differing significantly between them. Pathway analyses revealed that homologous recombination is defective in about half of the tumors, and NOTCH and FOXM1 signaling are involved in the pathophysiology of serous ovarian cancer. The study also identified that BRCA1/2 mutationsThe Cancer Genome Atlas (TCGA) project analyzed 489 high-grade serous ovarian adenocarcinomas (HGS-OvCa) and 316 of these tumors for exome sequencing, revealing that TP53 mutations are present in nearly all cases (96%), while nine other genes show low but recurrent somatic mutations. The study identified 113 significant focal DNA copy number aberrations and promoter methylation events in 168 genes. Four transcriptional subtypes, three microRNA subtypes, four promoter methylation subtypes, and a survival-associated transcriptional signature were identified. Pathway analyses indicated that homologous recombination is defective in about half of the tumors, and NOTCH and FOXM1 signaling are involved in the pathophysiology of serous ovarian cancer. Ovarian cancer is the fifth leading cause of cancer death among women in the US, with 21,880 new cases and 13,850 deaths estimated in 2010. Most deaths are due to advanced-stage, high-grade serous ovarian cancer. Standard treatment includes aggressive surgery followed by platinum-taxane chemotherapy, but recurrence occurs in about 25% of patients within six months. The five-year survival rate is 31%. Approximately 13% of HGS-OvCa cases are due to germline mutations in BRCA1/2, while the majority are due to somatic aberrations. The TCGA researchers conducted comprehensive genomic and epigenomic analyses to identify molecular abnormalities influencing pathophysiology and treatment. Microarray analyses provided high-resolution measurements of mRNA, miRNA, DNA copy number, and DNA promoter methylation for 489 HGS-OvCa tumors. Massively parallel sequencing provided whole-exome DNA sequence information for 316 samples. The study identified 19,356 somatic mutations, with TP53 mutated in 303 of 316 samples. BRCA1 and BRCA2 had germline mutations in 9% and 8% of cases, respectively. Six other genes were found to be statistically recurrently mutated. The study also identified 50 focal deletions and 63 focal amplifications, with several genes involved in key pathways such as RB1, PI3K/RAS, and FOXM1. The study identified four transcriptional subtypes of HGS-OvCa, with survival duration differing significantly between subtypes. A 193-gene transcriptional signature was defined to predict overall survival. The study also identified three miRNA subtypes, with survival duration differing significantly between them. Pathway analyses revealed that homologous recombination is defective in about half of the tumors, and NOTCH and FOXM1 signaling are involved in the pathophysiology of serous ovarian cancer. The study also identified that BRCA1/2 mutations