How p53 gene mutates matters to survival, cancer researchers find

A new study at Sunnybrook has shone light on a well-known but mysterious gene that plays a key role in the growth of cancer.

Genes contain blueprints for making proteins, the molecules that actually carry out tasks in a cell. In the case of the p53 gene, it codes for making a protein known as p53, which tells cells to grow or not. In particular, this protein helps stop tumours from growing (It’s called a tumour suppressor gene.)

Scientists and doctors have known about p53 for a long time, and that it plays a role in halting tumour growth.

But, the p53 has remained rather mysterious. Even though doctors have been aware that the p53 gene is the most frequently mutated gene when a person is diagnosed with cancer, and collect information about what mutations are present, they haven’t really known how best to use that information in their clinics.

The new Sunnybrook study looked at decades of DNA analyses of the p53 gene in cancer patients and compared the survival data with how specific p53 gene mutations affect the way p53 protein works.

The Sunnybrook study has now found that there’s a big variation in survival rates in men with stomach or brain cancer — and it has something to do with how much of the activity of the p53 protein is lost due to a specific mutation.

It’s not just that it is mutated. It’s how it has mutated that matters to survival. Doctors can now look more closely at the gene and use the information to help discuss treatment options with patients and keep a closer eye on others who are at higher-risk for tumour growth.

“If p53 is mutated but still working at about 5 per cent, that is good news for patients,” said Dr. Jean Gariepy, a senior scientist in Physical Sciences at Sunnybrook Research Institute. “If it’s known that p53 will do some of the work to suppress the tumour growth, perhaps other harsh forms of treatment can be avoided and the tumour can still be controlled.”

Think of it like a cellphone battery, Dr. Gariepy said.

“If you have 5 per cent battery left, you can still call 9-1-1. You can still send a text message. It’s only when you actually reach 0 per cent battery that you can no longer use the cell phone.”

The same seems to be the case with p53. Some mutations result in a p53 form that is still working pretty well, while other mutations cause p53 to not work at all.

The researchers have now put together a chart of all the known p53 mutations observed in the clinic and categorized them based on their “battery power”.

“People with mutations that lead to a totally idle p53 have a poorer survival outcome and therefore might be considered for more aggressive treatment,” said Nicholas Fischer, a PhD student in the lab of Dr. Jean Gariépy at SRI and lead author of the study.

The study is a great step towards more personalized treatment, he said.

“We hope this data will help oncologists and their patients make better informed decisions about their care plan,” Fischer added.