The culprit is a single mutation out of 3 billion nucleotide pairs that make up the genetic code of the tumor. The mutation is present in every granulosa cell tumor, a rare and often untreatable form of ovarian cancer that affects about 5 percent of ovarian cancer patients, according to a study that appears in the June 10 online issue of the New England Journal of Medicine.
The discovery, made using state-of-the-art gene-sequencing technologies, may mark the beginning of a new era of cancer genomics, in which the complete genetic sequence of cancers and the mutations that cause them can be identified, researchers said.
For women with granulosa cell tumors, the precise identification of the mutation may help in developing new, badly needed treatments.
'This is really a two-fold discovery,' said lead study author Dr. David Hunstman, a genetic pathologist at the BC Cancer Agency and Vancouver General Hospital and an associate professor at the University of British Columbia.
'It clearly shows the power of the new generation of DNA sequencing technologies to impact clinical medicine, and for those of us in the area of ovarian cancer research and care, by identifying the singular mutation that causes granulosa cell tumors, we can now more easily identify them and develop new ways to treat them,' he added in a university news release.
In the study, researchers decoded four granulosa cell tumors using 'next generation' sequencing machines that decode billions of nucleotides at rapid speed and new computer techniques to quickly assemble the data.
While most types of cancer, including ovarian cancers, have a broad range of genetic abnormalities, researchers found a mutation in a single nucleotide in the FOXL2 gene in every sample.
The research team further validated the findings by examining additional tumor samples from across Canada and around the world.
In the past, analyzing the sequence of a tumor was a laborious process, and most studies could only look at one or only a few of the 20,000 genes in the human genome. The new sequencing technologies allow scientists to look at all at once.
'This task would have been unfathomable in terms of both cost and complexity even two years ago,' said Dr. Marco Marra, director of the BC Cancer Agency's Genome Sciences Center.
Researchers chose granulosa cell tumors because, unlike other cancers, they are 'clinically homogenous,' Huntsman said.
'This cancer is unique,' said Dr. Dianne Miller, a gynecologic oncologist at BC Cancer Agency and Vancouver General Hospital. 'For patients with this tumor type, it means they should all have the same response to the same treatment. And now that we have this pathway, we can look for existing cancer drugs that might work on this particular gene mutation to make the cancer disappear.'