Gene defect promotes aggressive forms of ovarian cancer

CANCER RESEARCH UK scientists have discovered how mistakes in a key gene drive the early stages of aggressive ovarian cancers. This could improve diagnosis of aggressive forms of the disease and lead to new treatments, according to a study published in the Journal of Pathology this month.

A team of researchers, from Cancer Research UK's Cambridge Research Institute, originally set out to discover how the presence or absence of the TP53 gene affect survival and treatment response for high grade serous1 ovarian cancer - the most common type of ovarian cancer in UK women. Instead, they made the exciting and surprising discovery that defects in this gene were present in nearly all the women studied with this type of ovarian cancer.

The discovery that such a high proportion of women have a mutation in this gene led the scientists to conclude that TP53 mutations are an important early step in the development of this disease.

The researchers found the mutations by scanning the gene in the tumours of 145 women with aggressive ovarian cancer. Most of the samples were from the Australian Ovarian Cancer Study, one of the largest population-based studies of ovarian cancer in the world2.

These results also show for the first time that these aggressive ovarian cancers have the highest known rate of TP53 mutations of any solid tumour.

Lead author Dr James Brenton, from Cancer Research UK's Cambridge Research Institute and an ovarian cancer clinician at Addenbrooke's Hospital, said: "Our findings help to explain the link between TP53 and aggressive ovarian cancer, showing how faults in this gene are a key step in the development of this disease. We now want to look at how we can target this fault with new treatments for aggressive ovarian cancers."

The TP53 gene codes for a protein called p53, which in normal cells is activated in response to cell damage and one of its functions is to order cells to die when DNA damage is beyond repair. It's critical that p53 functions normally to prevent genetic mistakes from accumulating in cells, which can lead to cancer. The p53 protein is missing or faulty in the majority of cancers.

Ovarian cancer is the fifth most common cancer in women in the UK, each year around 6,600 women are diagnosed with the disease. Around 40 per cent of women will survive the disease for at least five years after diagnosis, but if the disease is diagnosed earlier this increases to over 70 per cent.

Dr Helen George, head of science information at Cancer Research UK, said: "These really important laboratory findings could have a significant impact for ovarian cancer patients in the future. Cancer Research UK scientists co-discovered the p53 protein around 30 years ago. Understanding how faults in the TP53 gene this gene drive the aggressive forms of ovarian cancer could lead to new more targeted treatments for women with this disease. "