To make a quantum leap in medical research you generally need the so-called ‘ducks’ to align – unmet patient needs, new technology, expertise and funding, mixed with serendipitous timing.

By Professor Rodney Scott

To make a quantum leap in medical research you generally need the so-called ‘ducks’ to align – unmet patient needs, new technology, expertise and funding, mixed with serendipitous timing.

In our case, we have just delivered a breakthrough in the approach to sequencing of DNA for breast and ovarian cancers, which will have significant implications for scores of women who are concerned about familial risk.

Around three years ago we saw what was developing in terms of technological breakthroughs in our ability to sequence DNA. We realised that we had to acquire this technology to improve our ability to screen people for their genetic risk of breast cancer. We were fortunate enough to acquire funding from a variety of sources to buy the necessary equipment.

At the same time we enticed Dr Cliff Meldrum back from Melbourne where he’d been developing new approaches to identifying genetic change in women at risk of breast cancer.

We handed the equipment over to Cliff. Two years later it’s working!

From my perspective, having Cliff’s technical ability and the right technology has set the scene for our Pathology Service laboratory (The Hunter Area

Pathology Service division of Pathology North) to be appointed the first NATA-accredited facility in the country to test for breast cancer susceptibility using this diagnostic technology.

In England, the University of Cambridge was going through a similar process but we were the first to complete a validation study to show our approach was viable. The study looked at 400 to 500 samples we had previously tested by the then current methodology.

The old sequencing technology dated back to 1975, although there had been incremental improvements. The new equipment represents an exponential improvement,

It provides a quantum leap in our ability to offer a service when previously we had no potential to expand and cater for more women, nor was there the capacity to streamline data analysis from the old technology because it was so labour intensive.

The new system is considerably faster because we can test up to 40 people in parallel instead of one at a time. It’s less hands-on in the laboratory, has greater through-put, more efficiency.

The other thing that’s changed is data interpretation. It’s a lot quicker to identify changes in these genes now than previously.

It comes at a time when public awareness has increased rapidly. The Angelina Jolie story served to increase this enormously and drive demand from women across the country wanting the testing done.

There’s increased recognition that certain types of breast cancer are likely to be associated with germline changes within genes that had hitherto not been fully appreciated. The same genes are associated with ovarian cancer risk.

In the case of ovarian cancer, this is normally detected late. If women know they have a familial risk through the BRCA 1 or BRCA 2 mutations it can have implications for therapeutic choices.

These genes can be transmitted through several generations of males, and for women with BRCA1 there’s a huge implication to risk. A father can pass the trait onto his son, the son passes it onto his daughter, yet both the father and son may have nothing to identify that they are carriers.

In our genetic sequencing we are looking for something that could cause the disease. There’s lots of variation – the challenge is finding which variants are actually associated with breast and ovarian cancer.

It’s like a detective story trying to work out what’s important for personal risk.

The process we have developed is truly translational, crossing from basic scientific research to clinic implementation. It’s a perfect example of technology that was sitting in a research environment now translated into a diagnostic clinical utility.

It will allow more women more access to testing. It will give more timely results, which will reduce stress. Our pathology service has extended interstate and internationally, going as far as North America and Northern Europe.

The hard work has certainly paid off for women at risk, and from here we can move onwards to other familial cancer syndromes such as inherited predispositions for colorectal cancer.

* Professor Rodney Scott is co-leader of HMRI’s Information Based Medicine research program. HMRI is a partnership between the University of Newcastle, Hunter New England Health and the community.