Detailed 'genetic landscape' of ovarian cancer revealed

In collaboration with Adfero

US scientists have published the most detailed genetic analysis of ovarian cancer to date, following a large-scale analysis of tumour samples. Although the researchers did not identify new genes involved in the disease, the work revealed a "remarkable degree" of DNA disorder in ovarian cancer, according to the authors.

The Cancer Genome Atlas (TCGA) Research Network carried out the study, which examined samples from 500 patients with an aggressive form of ovarian cancer called high-grade serous adenocarcinoma.

The detailed analysis revealed that around 96 per cent of all tumour samples had faults in a gene called TP53, which carries the genetic code needed to make a tumour suppressor protein that normally prevents the formation of cancer. This confirms earlier work by Cancer Research UK scientists, which first showed the link between TP53 and this type of ovarian cancer.

When TP53 is faulty, the resulting protein is unable to function properly and ovarian cancer cells are allowed to grow uncontrollably.

The researchers, whose findings are published in the journal Nature, also confirmed a number of less common faults in other genes.

Dr Francis Collins, director of the National Institutes of Health, said: "This landmark study is producing impressive insights into the biology of this type of cancer. It will significantly empower the cancer research community to make additional discoveries that will help us treat women with this deadly disease."

The researchers also believe that their findings could lead to new ways to assess a patient's chances of surviving this type of ovarian cancer, which accounts for about 70 per cent of all ovarian cancer deaths.

They identified patterns for 108 genes which were associated with poor survival, as well as 85 genes linked to better survival.

Patients whose tumours had gene patterns associated with poor survival lived for 23 per cent less time than those whose tumours did not have these patterns.

The study also confirmed the role of the BRCA1 and BRCA2 genes in ovarian cancer.

Approximately 22 per cent of the tumour samples had faults in these genes. The analysis also revealed that ovarian cancer patients with BRCA1 or BRCA2 faults were more likely to survive for longer than patients with other faults in their DNA.

The exception was in patients whose BRCA genes had a DNA alteration called methylation, as opposed to a specific fault in the code of DNA. Women with this alteration to their BRCA genes did not survive any longer than patients with other faults in their DNA. This suggests that survival depends on the type of change in the BRCA genes.

Dr Harold Varmus, director of the National Cancer Institute, which jointly funds and manages the project alongside the National Human Genome Research Institute (NHGRI), said: "Cancer researchers can use this comprehensive body of information to better understand the biology of ovarian cancer and improve the diagnosis and treatment of this dreaded disease."

The study also suggests that around half of women may benefit from taking a new type of targeted treatment called a PARP inhibitor. These drugs are designed to target specific gene faults by preventing the tumour cells' DNA repair machinery from working effectively and causing the cells to die.

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

Cancer Research UK scientist Dr James Brenton first showed that TP53 faults are present in almost all cases of this type of cancer. Of this new research, he said: "This work adds a lot of extra detail to the genetic survey of ovarian cancer. While we already knew about many of the genes highlighted in this study, this is the most comprehensive map yet, and will help towards future progress in diagnosing and treating this disease.

"It confirms that - aside from a few common faults - the DNA in ovarian tumours is remarkably variable. The TCGA project is not finished and there are more important data still to come from DNA sequencing of most of the cancers. As more advanced DNA sequencing technologies get cheaper, we will see much more genetic detail emerge about ovarian cancer. This will help us work out the specific DNA faults in each woman's tumour and allow us to treat them individually."