New breakthroughs in how gene mutations form and lead to cancer are being driven by NSW research, with five studies now published thanks to one Cancer Institute NSW grant.
“This project has launched a whole new research direction for me,” says Dr Jason Wong, Associate Professor in the School of Biomedical Sciences at the University of Hong Kong and formerly at UNSW Sydney.
‘Scarcity of Recurrent Regulatory Driver Mutations in Colorectal Cancer Revealed by Targeted Deep Sequencing’ was published in the June issue of Journal of the National Cancer Institute Cancer Spectrum.
Led by Dr Wong and his team in NSW, the study could help clinicians treating bowel cancer.
But the exciting development is only the latest output from the inaugural ‘Big Data, Big Impact’ grant, awarded in 2013.
Usually when cells in the body divide, the new cells are exact copies of the old cells. When this process goes wrong, the new cells are slightly different from the old ones.
This change happens in the genetic material (DNA) inside the cells, and is called a mutation.
While most cells with mutations will die or not cause any problems, a very small number will go on to cause cancers.
“We are seeking to identify the processes that drive mutation formation and those that result in cancer initiation in patients,” explains Dr Jason Wong.
“I hope that our findings can be translated to provide patients with more targeted treatment.”
Big data
Six years ago the ‘Big Data, Big Impact’ grant was awarded to Dr Jason Wong, Dr Luke Hesson and Associate Professor John Pimanda from the Lowy Cancer Research Centre, UNSW, with Dr Joe Thurbon from Intersect.
The team commenced one of the largest projects of its kind – exploring the non-coding portion of the human genome to understand its role in causing cancer.
“The grant came at the perfect time to kick-start this project,” Dr Wong explains.
“Not only from a funding perspective, it also gave us the platform to engage with Intersect (the NSW eResearch organisation), providing us with the computational resources to undertake the research.”
They successfully identified recurrent mutations at key functional non-coding regions in cancer, and the team were awarded stage two funding in 2014.
Dr Wong says grant programs focusing on big data have the potential to accelerate important collaboration and research programs across NSW.
Big impact
Five papers have now been published by Dr Jason Wong and his team, all linked to the ‘Big Data, Big Impact’ grant.
“It started with the 2014 Genome Biology paper, where we first developed a computational method to find mutations in gene regulatory regions,” Dr Wong says.
“When we did this, we noticed some unusual patterns in the way some gene regulatory regions are mutated in cancer.”
Their investigations led to three further papers published in Nature, Cell Reports and Nucleic Acids Research describing the discovery and analysis of new biological processes.
“They define how our genomes can become mutated, and how our cells try to repair DNA damage.”
Dr Wong says this work is helping to define which mutations in gene regulatory regions are most likely to be cancer causing, and it is now helping to find those mutations in bowel cancer.
How is the latest study making a difference?
“This study was particularly interesting to me because we were going to be using cancer samples collected
locally to generate a dataset to answer an important research question,” Dr Rebecca Poulos says.
Dr Poulos, NHMRC Early Career Fellow at the Children’s Medical Research Institute, began working with Dr Jason Wong in 2014 – enticed by the prospect of working in big data analysis in cancer research.
“The goal of this study was to sequence regulatory regions in almost 100 bowel cancers – to find out whether cancer-causing mutations may be located there.”
They could then inform clinicians about whether it will be useful to include the sequencing of regulatory regions in cancer panel testing for bowel cancer.
“We sequenced these cancers and found that cancer-causing mutations in these regions seem to be very rare – including them in cancer panel testing is unlikely to have clinical utility at this stage.”
“Interestingly, they appear to be rarer than in other cancer types that we have studied, and we’ve been doing other research projects to work out why that may be.”