"Like all cancers, ovarian cancer results from genomic derangements," said Eric D. Green, M.D., Ph.D., NHGRI director. "The efforts of TCGA are confirming that the more we learn about genomic changes in tumor cells, the more we will be able to care for the people affected by cancer."

The results of this study support the existence of four distinct subtypes of the disease, based on the patterns seen in the transcription of RNA from DNA. They also support the existence of four related subtypes based on the patterns of DNA methylation-a chemical reaction in which a small molecule called a methyl group is added to DNA, changing the activity of individual genes. These patterns likely reflect the functional changes associated with ovarian serous adenocarcinoma, but are not strongly associated with survival duration.

Mutations in BRCA1 and BRCA2 genes, which are associated with some forms of breast cancer, also confer increased risk for ovarian cancer. In this study, approximately 21 percent of the tumors showed mutations in these genes. Analysis of these tumors confirmed observations that patients with mutated BRCA1 and BRCA2 genes have better survival odds than patients without mutations in these genes. Importantly, investigators identified that the mechanism by which the BRCA1 and BRCA2 genes become defective also relates to survival. If either of the BRCA1 and BRCA2 genes is mutated, there is improved survival duration. However, if BRCA1 activity is instead reduced by methylation, there is no improved survival duration.

"The integration of complex genomic data sets enabled us to discover an intricate array of genomic changes and validate one specific change that occurs in the vast majority of all ovarian cancers," said lead author Paul T. Spellman, Ph.D., Lawrence Berkeley Lab, Berkeley, Calif. "Significantly, we have also found new information regarding the role that the BRCA1 and BRCA2 genes play in determining survival."

In this latest study, the TCGA researchers built upon the approach they used in 2008 to characterize the genome of gliobastoma multiforme, the most common form of brain cancer.

Source: NIH/National Cancer Institute