Dr Paul Yeh (left) with other members of the Genetics and Molecular Pathology Laboratory – Monash Health
An evolving technology that can screen for more than 600 different gene fusions (two or more genes joined together) in a single test, has been approved as a diagnostic tool at Monash Health.
A study by a team of researchers at Monash Health confirms that the next-generation sequencing (NGS) RNA (messenger carrying instructions from DNA) fusion panel reliably identified gene arrangements that drive blood cancers. This finding was published in the article “Next-generation sequencing RNA fusion panel for the diagnosis of haematological malignancies” in the Royal College of Pathologists of Australasia journal Pathology.
Research lead Dr Paul Yeh, a consultant haematologist, explains that NGS can detect a wide range of gene fusions, even rare or unexpected ones.
The traditional diagnostic method, which includes FISH (fluorescence in situ hybridisation) or PCR (polymerase chain reaction), can only detect specific, pre-known fusions.
‘The potential of this technology can now allow us to profile blood cancers more comprehensively. This will give us better information to help us manage blood cancer patients, including diagnosis of difficult cases,’ he says.
How does the next-generation sequencing (NGS) RNA fusion panel work?
‘Fusions or rearrangements in blood cancer are usually two pieces of genetic material that are abnormally “fused” together and go on to produce an abnormal protein. RNA carries the instructions that make these fusion proteins. Hence, the NGS RNA fusion panel looks for these fusions from patients with suspected blood cancer using RNA from patient blood or bone marrow.
‘Once we have RNA, the NGS technology allows us to simultaneously generate and read millions of short genetic fragments from a single patient. We use specialised bioinformatics software to analyse these sequences and identify any fusions of genes that shouldn’t normally be joined. These results can help us pinpoint specific gene fusions that cause blood cancers and thus can aid in the diagnosis, prognosis and even the selection of targeted therapies,’ Dr Yeh explains.
Monash Health’s study confirms the reliability of the NGS RNA fusion panel as a diagnostic tool
The study was performed at Monash Health between the Genetics and Molecular Pathology (GMP) laboratory, headed by Program Director of Pathology Dr Beena Kumar and the Haematology department, headed by Clinical Director Professor Jake Shortt.
Dr Trung Ngo, a haematology laboratory trainee and Anna Fong Na Goh, a medical scientist in GMP, led the work and are co-first authors on the study under Dr Yeh’s supervision as clinical lead for Molecular Haematology.
The study was funded by a Monash Haematology Research grant awarded to Dr Ngo. The team received cases from a haematology unit in Austin Hospital in Victoria and South Australia as part of this collaboration.
Dr Yeh explains that the team had to perform multiple experiments to ensure that the test was optimised for diagnostic use and that the results were robust and reproducible.
‘Although a challenge, Trung and Anna’s persistence has enabled successful optimisation, and thus, our manuscript has provided a blueprint that can be adopted by other laboratories around the world that wish to set up RNA fusion testing in the future,’ he says.
Looking to the future
Dr Yeh notes that while there are limitations to this technology in its current state, there are exciting opportunities for improvements.
NGS takes longer, from a few days up to four weeks, compared to traditional methods, which take hours to days, due to the complexity of sequencing and data analysis. The team, however, is working to develop more efficient workflows to improve the turnaround time.
It is currently not suitable for monitoring cancer therapy when looking for small amounts of residual cancer. However, further work is ongoing to see if the sensitivity of the NGS RNA fusion panel can be increased.
Patients at Monash Health can now access Medicare reimbursement for this test with the recent approval from the National Association of Testing Authorities (NATA).
Dr Yeh confirms that this test will be offered to our patients as part of the standard of care in diagnosing blood cancers, as well as requests from external centres.
‘Given its potential, ongoing research will be underway in larger patient cohorts in an attempt to discover new fusions in subsets of blood cancer patients,’ Dr Yeh says.
Congratulations to Dr Yeh and the team for advancing care and hope for blood cancer patients at Monash Health!
