Tumor Mutational Burden (TMB) is a biomarker that has gained prominence in modern cancer care. It is a quantifiable measure taken from a patient’s tumor, providing insight into the cancer’s genomic instability. Understanding TMB helps doctors make informed decisions about personalized cancer treatments.
What Tumor Mutational Burden Means
Tumor Mutational Burden is a metric that counts the total number of genetic changes, or mutations, found within a tumor’s DNA. These mutations are somatic, meaning they are acquired during a person’s lifetime and are not inherited. The final TMB value reflects the volume of these alterations in the tumor’s genetic code.
A higher count of mutations suggests the tumor is genomically unstable, often due to defects in DNA repair mechanisms. This high rate of change leads to the creation of many abnormal proteins, known as neoantigens, that are not present in normal cells. These unique, altered proteins essentially act as foreign flags on the surface of the tumor cell. The number of neoantigens directly correlates with the tumor’s TMB.
Measuring TMB in Cancer Cells
Quantifying TMB requires specialized genetic analysis of a tumor tissue sample, most commonly using Next-Generation Sequencing (NGS). While Whole Exome Sequencing (WES) provides the most comprehensive picture by analyzing all protein-coding DNA, it is often impractical for routine clinical use. Therefore, laboratories usually employ large, targeted gene panels which sequence a defined subset of the tumor’s DNA.
The result is calculated by counting the number of somatic mutations detected and then normalizing against the total size of the genomic region sequenced. This final TMB score is reported as the number of mutations per megabase (mut/Mb) of DNA analyzed. Tumors are categorized as having a high TMB, with a common clinical cutoff being 10 or more mutations per megabase, or a low TMB, which is below that threshold.
TMB and Personalized Cancer Treatment
The primary clinical application for TMB is its role as a predictive biomarker for response to immune checkpoint inhibitors. These immunotherapy drugs work by removing the “brakes” that cancer cells place on the immune system, allowing immune cells to attack the tumor. A high TMB indicates a greater number of neoantigens, which makes the tumor more visible to the immune system.
When the immune system’s checkpoints are blocked by the drug, the high number of neoantigens makes the tumor an easier target for the activated immune cells. Doctors utilize this information to personalize treatment plans, often selecting checkpoint inhibitor therapy for patients whose tumors show a high TMB score. The ability to predict a patient’s likelihood of benefiting from this specific class of drugs makes TMB a valued tool in guiding therapeutic decisions across several cancer types.