FAST FACTS: TUMOUR MUTATIONAL BURDEN TESTING
Dr Nicole Rossum
Understanding Tumour Mutational Burden (TMB) Testing
Tumour Mutational Burden (TMB) is a measure of the total number of somatic mutations found in the DNA of cancer cells.
It’s expressed as mutations per megabase (mut/Mb) of DNA sequenced.
It reflects how many genetic changes have occurred in the tumour’s genome.
Why Test for TMB?
Tumours with higher mutational loads:
- Are more likely to generate neoantigens
- Increase immunogenicity
- Improve likelihood of response to immunotherapy, especially immune checkpoint inhibitors (anti–PD-1/PD-L1 therapies)
A high TMB is commonly defined as ≥10 mut/Mb, though some tumour types may benefit at higher thresholds.
Clinical Relevance
TMB testing is recommended for:
- Advanced, unresectable, or metastatic solid tumours
- Cases with no satisfactory alternative treatment options
- Identifying candidates for immune checkpoint inhibitor therapy
KEYNOTE-158 Trial:
- Studied pembrolizumab in previously treated, advanced solid tumours
- Patients with TMB-high (≥10 mut/Mb) had a 29% response rate vs. 6% in non-TMB-high
- Led to regulatory approval for pembrolizumab in TMB-high tumours, regardless of histology
NGS-Based TMB Testing Now Available at Ampath
Ampath offers Next Generation Sequencing (NGS) based TMB testing
Can be requested:
- Individually
- As part of the Oncomine™ Comprehensive Assay Plus
TMB NGS Testing Panel Overview
Test Mnemonic: TMB
Clinical Indication: Identify oncology patients for immune checkpoint inhibitor therapy
Specimen Type: FFPE tissue: 8–12 normal slides (not charged), 10 micron thick unstained recuts in Eppendorf tube or paraffin block
Turnaround Time: 14 working days
Contact for more info: ngs@ampath.co.za