TEST CODE: 008866
DIAGNOSTIC TEST FOR: TUMOUR MUTATIONAL LOAD ANALYSIS
TURNAROUND TIME: 10–21 calendar days (14 days on average)
PREFERRED SPECIMEN: 3mL whole blood in a purple-top tube
ALTERNATE SPECIMENS: DNA or saliva/assisted saliva
Tumour Mutational Load Analysis
What is Tumour Mutational Load?
Cancer is a complex disease, caused by a wide range of genetic mutations that can be present in many combinations.
Tumour mutational load (TML), or tumour mutational burden, is a measure of the number of mutations within a tumour genome. TML can vary greatly between tumour types, ranging from just a few to thousands of mutations in a tumour.
What is the Tumour Mutational Load Analysis?
Our Tumour Mutational Load Analysis conducts a genetic analysis of 409 cancer ‘driver’ genes, which are genes that allow cancer cells growth advantages. We combine this analysis with all previously available information on your tumour from histology reports, to generate a TML score. The TML score is an indication of mutational load per megabase of DNA. This will then be classified into a low or high TML, providing a likelihood of your response to immunotherapies.
High TML = More likely to respond to Immunotherapy
Low TML = Less likely to respond to Immunotherapy
TML is emerging as an important indicator of sensitivity to immune checkpoint inhibitors and may indicate your likely response to immunotherapy. The use of immune checkpoint inhibitors in tumours with a higher TML has been shown to be associated with improved overall survival rates. TML has been shown to more accurately indicate response to PD-1 and PD-L1 blockade immunotherapy, than PD-1 or PD-L1 expression as measured by immunohistochemistry (IHC).
How can I use the results from the Tumour Mutational Load Analysis?
Our Tumour Mutational Load assay has been designed in response to the need to determine if treatment utilising immune checkpoint inhibitors is likely to be of benefit in your particular clinical circumstances. The TML Analysis analyses over 409 genes and some specific genes are looked at in depth, including TP53, KRAS, PIK3CA, PTEN, STK11 and JAK1/JAK2. Mutations in these genes may also predict response to immunotherapy.
– TP53– or KRAS-mutated tumours show prominently increased mutation burden and have shown remarkable clinical benefit to PD-1 inhibitors.
– Alterations in KRASand PIK3CA are associated with complete or partial response to immune checkpoint blockade.
– Non-small-cell Lung Cancers with mutations in both KRASand STK11 tend to respond poorly to anti–PD-1 therapy, compared to those with KRAS mutations alone. Loss of PTEN is associated with resistance to PD-1 blockade.
– Mutations in JAK1/JAK2are associated with developing resistance following initial clinical response to PD-1 blockade.
What is PD-1 and PD-L1 blockade immunotherapy?
Immunotherapy is a form of treatment that utilises your own immune system to fight cancer cells. Immunotherapies may slow the growth and spread of cancer cells, by helping the immune system destroy existing cancer cells. The main types of immunotherapy can be divided into treatments using monoclonal antibodies, nonspecific immunotherapies and cancer vaccines. Immunotherapies can target cancer cells in a variety of ways, including using antibodies to:
– Attach to cancer cells to ‘flag’ your immune system to destroy that cell
– Slow the growth of cancer cells by blocking parts of the cell that enable them to grow
– Carry medicine, such as chemotherapy, directly to cancer cells
Cancers cells have clever ways of disguising themselves from being detected and removed by the immune system, by using the immune systems own checkpoints. Before an immune cell attacks it performs a check, looking for a signal to see if what it has encountered is part of our own body or not. This prevents “autoimmune” attacks and saves our own cells from being destroyed in an immune response. PD-1 is a checkpoint protein on immune cells called T cells. When T-cells interact with PD-L1, a protein on some normal (and cancer) cells, this acts as an “off-switch”. When PD-1 binds to PD-L1, it basically tells the T cell to leave the other cell alone. Some cancer cells have large amounts of PD-L1, which helps them evade immune attack. PD-1/PD-L1 Blockade immunotherapies work by blocking this interaction, preventing the cancer cells from telling the immune system not to attack, and allowing the immune system to detect the cancer cells.
What sample do you need to perform the Tumour Mutational Load Analysis?
To perform this test we require tissue that has been excised from your most recent biopsy. Previous or historical biopsies can also be used in most cases and a new biopsy is not usually required. This assay has been optimised to enable detection of variants using low-input FFPE samples such as fine needle biopsies and core needle aspirates.
If your most recent biopsy was more than one year ago or no biopsy is available, there are alternative testing options that we can consider to monitor your immune response, such as our TCR-Beta Assay. Please contact us to discuss alternative testing options.
Ready to take control of your treatment plan?
Genomed aims to educate patients and their families on their cancer types and empower them with the knowledge to take control of their treatment plans. As each patient’s case is unique, there is no “one size fits all” when it comes to testing. We encourage you to contact Genomed, and we can work with you and your oncologist/specialist, to determine what tests would benefit you.