Tumours are a lot like earthquakes. No two are the same, and just as quakes occur mostly along fault lines, scientists have discovered that tumours also have unstable regions hidden inside their genomes.
An Australian-led research group has conducted the most thorough analysis of pancreatic cancers, identifying four subgroups that differentiate tumours by their gene arrangements.
The discovery promises to improve the treatment of at least one group, about one in four patients, after the researchers noticed an existing class of chemotherapy drugs used to treat some breast cancers may also work on pancreas patients whose tumours have "unstable" genomes.
Their hunch appeared correct when they discovered four out of five study patients with this genetic signature responded to DNA-damaging drugs.
"Two of them had an exceptional response, which happens very, very rarely in pancreatic cancer. Their tumours went away completely," said the co-leader of the group, Andrew Biankin, who conducted the work at the Garvan Institute of Medical Research.
The results, published in the science journal Nature, represent one of most significant advances in pancreatic cancer – the fourth most common cause of cancer death – in 50 years
The ambitious project led by Professor Biankin and Sean Grimmond from the University of Queensland's Institute for Molecular Bioscience also signifies the first step towards personalised medicine, in which healthcare is customised to individual patients.
Previously, the group examined only a small portion of genetic material, the exome, which makes up about 1 percent of the genome.
While they found a "soup of mutations" that meant no two tumours were the same, it was difficult to know which were important – the equivalent of trying to predict where an earthquake may strike without knowing where fault lines sit.
This study looked at the whole genome of 100 patients' tumours – providing a detailed map of their tumour's entire genomic structure, revealing sections where bits of chromosomes had broken away and rearranged themselves.
"When you only sequence exomes you might see a fallen tree but you will not know whether it has fallen as the result of an earthquake, a storm, or other unknown factor," said Professor Biankin.
"When you sequence a genome you can tell whether a volcano, earthquake or local storm has taken place," he said.
Medical oncologist Lorraine Chantrill said the results suggested a specific class of chemotherapy drugs, known as platinum therapies, which damage tumour DNA and used to treat some breast cancers, may also work on pancreatic tumours with unstable genomes.
Team member Dr Marina Pajic said mice with unstable tumour genomes responded well to these drugs.
Dr Biankin, now based at the University of Glasgow in Scotland, said while countries such as Britain and the United States were investing significant resources to whole genome sequencing, Australia's health system had been slow to embrace personalised medicine and researchers faced many bureaucratic hurdles.
"When a tumour is removed from a patient it's the most informative piece of information and yet it sits in the theatre rotting. Then if you want to get samples for a clinic trial the pathology department says research isn't a priority," said Professor Biankin.
"The sequencing is the easy bit," he said.
Dr Chantrill said rarely did cancer doctors have access to genetic data to inform their patient's treatment.
"This sort of research is building the building block to allow that," she said.
The team will now use the findings to design a clinical trial that gave patients targeted treatment.
But Professor Biankin said Australia's health system needed to integrate patient care with pathology and research for personalised medicine to work.
Most pancreatic cancer patients do not respond to existing treatments and die within a year of being diagnosed, a survival rate that has not improved in 50 years.
