In this in-depth feature we explore how whole genome sequencing is moving rapidly from the bench to the bedside as research institutes around the country start to commercialise their expertise.

Clinicians can expect to learn much more about the variants and mutations underlying their patients’ disease and use that information to individualise therapy.

In Queensland, QIMR Berghofer has just launched a new company genomiQa that will specialise in whole genome somatic analysis of cancers.

Co-founder of genomiQa Dr Nicola Waddell said clinicians can increasingly expect to be treating cancers based on a genotype or phenotype rather than the tissue of origin.

“As an example, Keytruda has become the first drug to be FDA approved for all cancers with a specific mutation related to microsatellite instability.”

If similarly approved in Australia, Keytruda (pembrolizumab) may be used for a range of solid tumours including mesothelioma, colorectal cancer or endometrial cancers.

Dr Waddell said genomiQa’s clinical service would focus on identifying ‘actionable targets’ – well-characterised variants or mutations for which there were approved treatments.

But along with known mutations such as HER2, BRCA and ALK gene mutations, whole genome analysis will also help identify new potential targets.

“There will be immediate benefits to patients where there are known treatments. But we will also have the data to suggest other targets. For example, in non-small cell lung cancer the ALK gene can be fused with different gene partners. We hope to identify all those gene partners.”

genomiQa is still working through the NATA accreditation process and expects to be delivering clinical services by the end of the year. They are currently looking to establish partnerships with hospitals, doctors and pathology services.

Dr Waddell said while Medicare did not yet cover whole genome sequencing, genomiQa were working to keep the costs down and the service accessible.

Genomics for prevention

Meanwhile, a commercial spin-off from the Garvan Institute of Medical Research and its Kinghorn Centre for Clinical Genomics is expanding its offerings direct to consumers.

Originally focussed on the diagnosis of rare genetic diseases in children, and other germline mutations, Genome.One has just launched a whole genome sequencing and health assessment service to help individuals better understand and manage their future risk of disease.

Associate Professor Marcel Dinger, CEO of Genome.One, told the limbic the service was a natural progression in the delivery of precision healthcare.

“As genomics moves into the mainstream, it is no longer exclusively about diagnosis but also prevention and early detection.”

“We have taken a very conservative approach to what clinically significant information can be derived from the genome today and have chosen the genes we analyse very carefully. Any pathogenic variation in genes would need to have a substantial chance of causing disease,” he said.

Together with a comprehensive health assessment including resting and stress ECG and pathology testing, whole genome sequencing at Genome.One offers predictive information on 31 cancers, 13 cardiac conditions and five other hereditary conditions.

Professor Dinger estimates only 5-10% of people will have a specific risk identified, but for those individuals it will be an ’incredibly useful piece of information’.

For example, it may provide the evidence – and motivation – for more frequent cancer screening or other preventive health measures.

He says the service will attract people with a family history of cancer or heart problems along with the curious and the health conscious, but is a worthwhile step towards redressing the healthcare system’s unsustainable focus on treatment over prevention.

Genome.One is also offering a ‘pioneering product’ in pharmacogenomics – identifying the gene mutations that influence an individual’s ability to metabolise some 220 medications.

Identifying faulty genes responsible for enzyme deficiencies known to put patients at risk of serious adverse events during anaesthesia was just one example, he said.

“In the future, fewer drugs will be prescribed without knowledge of a person’s metabolism and potential for adverse reactions. Price is the only thing standing in the way.”

Professor Dinger said clinicians should be considering which of their clinical decisions could be influenced by additional genetic information.

“If you have a concerned patient with cancer in their family, does that extra layer of information influence screening? When prescribing a particular drug, is your patient at a biochemical disadvantage because of their genetic profile?”

Ethics and education

Professor Dinger says he acknowledges the potential risks in over-interpreting the genome, which is why their service integrates all other relevant information and findings are filtered back to patients through consultations with health professionals.

Guidance from the Royal College of Pathologists of Australasia says genomic sequencing doesn’t necessarily introduce any new ethical issues but magnifies their importance ‘due to the volume of information that these tests yield’.

Dr Waddell, who co-leads a project on the ethics, legal and social implications of genomics for the Queensland Genomics Health Alliance (QGHA), said the principle of informed consent underpins genomic testing as it does any other area of medicine.

“Patients need to be fully aware of the nature of the testing and the potential outcomes.”

“Whole genome testing can also involve instances of incidental findings and we need ethical routes and pathways to allow for the flow of that information.”

She added that training the existing health workforce in the use and interpretation of genetic data was also required.

A suite of online postgraduate programs currently being developed by Queensland University of Technology’s Institute of Health and Biomedical Innovation should be available from 2018.

A Master of Diagnostic Genomics will provide an accreditation route for genetic scientists while Graduate Certificate and Diploma level programs will suit clinicians who wish to increase their confidence in, and knowledge, of genomics.

Taking advantage of technology

In Victoria, the Australian Genome Research Facility and University of Melbourne Centre for Cancer Research (UMCCR) have recently announced new capacity in genome sequencing.

UMCCR director Professor Sean Grimmond told the limbic they had the technology to be sequencing 30,000 patients per year.

“The technology is still developing very rapidly and the price is dropping. In 2010, it took a team of about 40 people seven or eight months and about $1million to sequence the genome of a patient with cancer. Now it takes just a handful of people and we can do dozens in a week for about $1,000 each.”

He said the Centre was piloting a number of projects, including in pancreatic and upper gastrointestinal cancers, and gearing up for accreditation to provide diagnostic grade information.

“We are very close to rolling out an approach especially for challenging or advanced patients in whom standard care has been exhausted.”

“The greatest opportunity will be seen when whole genome sequencing is used in those cancers where we have clear biomarkers and poor outcomes, in patients with recalcitrant cancers and in rare cancers.”

However in the absence of a large-scale, nationally coordinated funding effort, Australia was not yet fully equipped to integrate genomics into health care, he said.

“What we’ve seen in the UK is an injection of $30 million into the education of clinical and allied healthcare personnel so people are ready to work together on this. We need to get the clinical community in Australia ready to receive and exploit this opportunity for precision oncology.”

“The electronic health record is also vital to taking this forward.”

Professor Grimmond said France had announced an investment of €670 million to transform their healthcare system for the impact of genome sequencing. In contrast, Australia had committed $25 million.

He added that the genomics workforce in Australia was a tight knit community with a strong track record of working together on projects such as the genomic analysis of pancreatic cancer.

“Genomics research is very collaborative by nature. We are trying to implement genomics testing into routine patient care and we do that best by working together,” Dr Waddell said.