Next-generation sequencing (NGS) as a technology has been used in academic research for over a decade in various applications, and is now an exciting development in the field of diagnostics. NGS allows testing of multiple genes, targeted regions of the genome, or the full genome. It supports the uptake of precision medicine and understanding the complexity of diseases.
Australia’s Medical Services Advisory Committee (MSAC) recently recommended the reimbursement for a small gene panel using NGS to test for biomarkers on tissue specimens of non-small cell lung cancer (NSCLC). This is a huge step for patients around the country who were once affected by delays to diagnosis.
This article dives deeper into the concept of NGS and how it supports healthcare professionals with diagnosing life-threatening cancers and complex genetic disorders. It also examines why a reimbursement of NGS for NSCLC would be valuable if it were to come into effect.
In the Australian setting, NGS is still catching momentum, as current gene testing is often performed using sequential testing of clinically actionable biomarkers. What NGS allows is called massively parallel sequencing, to sequence multiple genes, multiple changes, for multiple samples at the same time. But bringing this testing in-house can be challenging for laboratories.
We spoke with Dr Bansi Sanghvi, Clinical Business Manager for Australia & New Zealand employed by Thermo Fisher Scientific in Australia, about NGS and why this new dawn of diagnostics is important. Dr Sanghvi explains the concept of NGS:
“NGS in simple terms allows you to look at the genetic sequence, whether it is the gene, multiple genes, or the whole genome. It allows you to read the code, or every nucleotide, of the genetic sequence.
So if you think about it as a book, you’re not just reading the front end and the back end of the book, but you’re actually reading the words in the book. And within those words, you’re decoding each and every letter of the word as well.
It provides much more information and is more sensitive and specific than PCR (polymerase chain reaction) technology.”
NGS technologies use different parameters to provide genetic information. Thermo Fisher Scientific’s Ion Torrent NGS technology looks for changes in pH generated by the incorporation of nucleotides into the DNA sequence, and the raw data is then converted to generate the genetic sequence for further analysis.
“We often say it’s the world’s most complex pH meter.”
As described by Dr Sanghvi, Ion Torrent NGS technology has been available in Australia (‘Research Use Only’) for many years, primarily being used in the clinical research setting. Recently, Thermo Fisher Scientific launched an end-to-end NGS system that provides results from sample to report in a day. Multiple genetic testing laboratories across Australia have adopted this system to detect somatic mutations in biopsies of many commonly occurring cancers such as lung, colorectal, melanoma, bile duct, brain cancers, myeloid disorders and more. The CE-IVD marked NGS system and test have received diagnostic use certification in many countries globally, and Dr Sanghvi is hopeful that this will be the case for Australia as well in the future.
Dr Sanghvi explains why NGS is such an effective tool in cancer research, specifically lung cancer where limited amount of biopsy sample is not sufficient for sequential single-gene testing.
“Until very recently, molecular testing undertaken in pathology laboratories was often performed for one gene at a time. So if a biopsy was identified as an adenocarcinoma through histopathological tests, the first step would be ‘Let’s test for one of the most common biomarkers such as EGFR’. If the biopsy is EGFR negative, you move on to test for the next biomarker and so on.
There has been a push to allow pathology laboratories to move from single-gene to multi-gene biomarker testing, so as to utilise the very limited biopsy and benefit from looking at multiple biomarkers at the same time rather than sequentially, and identifying personalised next steps as quickly as possible in the field of precision oncology.”
Dr Sanghvi welcomes MSAC’s recommendation to subsidise NGS for NSCLC.
“This is a game changer when it comes to the ability to use that limited biopsy, a very big challenge in lung cancer. It will not limit the testing of biopsies to only biomarkers such as EGFR, ALK, ROS, etc, but expand the testing to others such as METex14, as well as fusion targets such as NTRK and RET.”
NGS will allow testing for all these biomarkers simultaneously, using limited biopsy in a more cost-effective way:
“Panel testing is going to gain momentum and the size of those panels or the need for testing a number of biomarkers is going to be dictated by the complexity of the cancer and the clinical actionability of those biomarkers. You cannot have a one-size-fits-all approach for all cancers.
With cancers like NSCLC, turnaround time of results is critical and we are already seeing that many of these laboratories are now able to provide a NGS report within a few days using smaller gene panels in automated, rapid workflows.”
The next step is for the MSAC reimbursement recommendation to be approved, so that healthcare practitioners may start being able to access affordable NGS for NSCLC.
NGS is not just useful in the field of oncology, and is also used in understanding genetic mutations in complex diseases that benefit from massively parallel sequencing. Dr Sanghvi said:
“Rare diseases, paediatric cancers, inherited disorders, and even carrier screening for couples are other areas where NGS is now used. Carrier screening, for example, helps couples to detect any genetic risk by identifying if they are carriers for a potential disorder. This can highlight their risk in terms of a successful pregnancy or any potential impact it can have on their child.”
Australia is about to enter a new chapter when it comes to NSCLC diagnosis. Patients will be able to benefit from highly targeted precision medicine as the genetic make-up of their tumours is deciphered quickly and accurately by NGS, reviewing different possible genes commonly linked to the cancer when they have acquired mutations. As more drugs are being manufactured to target these genetic mutations, testing for these biomarkers simultaneously will allow patients to get access to the right drug as soon as possible.
