Ovarian cancer accounts for about three percent of all cancers in women. This histopathological image shows serous adenocarcinoma in bilateral ovaries. (source: Wikimedia)

Their work could lead to a day in which doctors treat high-grade serous ovarian cancer by detecting the aberrant genes in a patient, and targeting these genes with therapies that are most effective against the specific mutations. It could also guide the development of new pharmaceuticals that are specially tailored to fight mutations that cause ovarian cancer.

The project was conducted under the auspices of the The Cancer Genome Atlas, an effort led by the National Institutes of Health’s National Cancer Institute and National Human Genome Research Institute to improve cancer care by understanding the genetic causes of the disease.

Paul Spellman of Berkeley Lab’s Life Sciences Division is the corresponding author of the Nature article. Several other Berkeley Lab scientists contributed to the research, including renowned cancer researcher Joe Gray, a guest senior scientist in Berkeley Lab’s Life Sciences Division. The project required collaboration among experts across the nation in tissue analysis, genome sequencing, cancer genomics, and data analysis.

“The Cancer Genome Atlas is about giving a parts list to the cancer community. Clinicians can use the data to propel the next wave of discoveries, such as new cancer therapies and early-detection methods,” says Spellman. “We are the first to systematically catalog the genetic mutations associated with ovarian cancer.”

Ovarian cancer is the fifth leading cause of cancer death among women in the US, with almost 22,000 new cases and 14,000 deaths estimated for 2010 according to the National Cancer Institute. High-grade serous ovarian cancer, which begins in the cells on the surface of the ovary, accounts for 90 percent of all ovarian cancers and often remains undetected until it’s quite advanced.

The standard of care is aggressive surgery followed by platinum-taxane chemotherapy. After therapy, however, platinum-resistant cancer recurs in approximately 25 percent of patients within six months and the overall 5-year survival rate is 31 percent. Because of this, scientists are seeking potent and targeted ways to fight the disease, which requires a thorough understanding of its genetic roots.

To do this, The Cancer Genome Atlas program brought together scientists from a wide range of disciplines and research institutions. More than two dozen sites provided tissue samples of ovarian tumors. Scientists at other sites performed gene expression analysis, DNA sequencing, and other analyses. The resulting data was fed to two repositories and analyzed by members of the network including Berkeley Lab scientists.

Among their many findings, the team determined that the causes of ovarian cancer are not confined to changes affecting individual genes. Large structural changes in a cancer’s genome — in which genes are erroneously deleted or duplicated — are also important. Scientists knew that ovarian cancer genomes have gene copy errors, but they didn’t know these hiccups are such a big driver of the disease.