Tumor Mutational Burden (TMB)

Tumor Mutational Burden is a measurement of how many genetic mutations are present in the DNA of a cancer's cells, usually reported as mutations per million bases of DNA sequenced. A higher TMB generally means the tumor produces more abnormal proteins that the immune system can recognize, which can make some cancers more responsive to immunotherapy. Mesothelioma typically has a low TMB compared with cancers like melanoma or lung cancer.

Origin

The concept emerged from large-scale tumor genome sequencing projects in the 2000s and 2010s, including The Cancer Genome Atlas (TCGA). TMB became clinically important after 2014–2017 studies showed it predicted response to immune checkpoint inhibitors, leading the FDA in 2020 to approve pembrolizumab for adults with high-TMB solid tumors.

Significance in Asbestos Context

For mesothelioma patients, TMB is one of several biomarkers oncologists look at when deciding whether immunotherapy drugs such as nivolumab and ipilimumab are likely to help. Mesothelioma is generally a low-TMB cancer, which partly explains why responses to immunotherapy vary widely from patient to patient. Some tumors respond dramatically while others do not. Knowing your tumor's TMB, along with PD-L1 status and BAP1 mutation status, can help your medical team match you to standard treatments or clinical trials. Ask whether your pathology report or molecular profiling includes a TMB result, and whether the testing was done on tumor tissue or a blood-based (liquid biopsy) sample, because the two are not always interchangeable.

Example Sentence

When the oncologist explained why she was recommending combination immunotherapy, she pointed to the patient's tumor mutational burden and PD-L1 expression as factors that made response more likely.

Related Terms

Immunotherapy, PD-L1, BAP1, Checkpoint Inhibitor, Next-Generation Sequencing, Molecular Profiling

Notes

• Ask your oncologist whether comprehensive molecular profiling (which typically reports TMB) has been ordered on your tumor tissue, and request a copy of the report for your records.
• If TMB testing was not done at diagnosis, ask whether archived biopsy tissue can still be tested. This can open the door to clinical trials.
• Keep all molecular and genomic test results together with your pathology reports; these documents can be important both for treatment decisions and for documenting your diagnosis in a legal claim.
• Be aware that 'high' and 'low' TMB cutoffs vary by laboratory and by cancer type; ask your doctor what the result means specifically for mesothelioma.