What Is Tumor Mutation Burden?

The tumor mutation burden is simply the genetic fingerprint of cancer. Tumor mutations may seem like bad news, but modifications can also provide valuable information for cancer treatments.

Chemotherapies are powerful cell-killing drugs, but they also act on almost all dividing cells. Since cancer cells are the most proliferating cells, they are also most affected by chemotherapy. However, recently, the door to targeted therapies based on the different biology of cancer cells has opened with the discovery of predictive biomarkers. Biomarkers can reveal the details of a patient’s disease and progression and how they may respond to treatment.

Tumor mutation burden measures the number of mutations carried by tumor cells and the areas of focus that appear in biomarker research. In its simplest definition, tumor mutation burden is the total number of mutations in the tumor. By comparing DNA sequences from a patient’s complex tissues and tumor cells and using a set of sophisticated algorithms, the number of acquired somatic mutations found in tumors but not in normal tissues can be determined.

Unlocking The Potential of Tumor Mutation Burden

The efficacy of immunotherapies can be predicted with specific immune proteins expressed (presented) by the tumor and interacting with the immune system. Tumor mutation burden is a different biomarker in this sense and is derived only from mutations.

Given that mutations cause cancer, a high tumor mutation burden may suggest more aggressive cancer biology, but this is not true in all cases. Researchers have found that some tumors with more mutations may be more sensitive to immunotherapies. In other words, tumor mutation burden is a biomarker used to predict the efficacy of immunotherapies.

As cells begin to change, some of the mutations found in tumor cells will code for proteins found on the surface of these cells, known as neoantigens. These can make the immune system recognize the tumor as foreign.

Tumor mutation burden can also provide helpful information about why certain cancers respond better to immuno-oncological treatments (immunotherapies). Mutations due to sunlight or smoking tend to respond better to immunotherapy. Other tumors, such as pancreatic or colon cancer, have fewer mutations, so they may be less likely to respond to treatment.

However, the fact that the human genome has more than three billion base pairs presents researchers with an exciting challenge; How do we standardize a biomarker that is affected by many different factors?

Measuring Tumor Mutation Burden

Tumor mutation burden can be assessed using whole exome sequencing. Whole exome sequencing examines the coding regions of 21,522 genes and identifies tumor mutation burden based on 200 mutations in the tumor exome.

To be clinically decisive, tumor mutation burden must have consistent standards for measurement and performance, but this presents a challenge.

Currently, there is no standard way to quantify or report tumor mutation burden, but we are optimistic that this will be possible in the future. Writing data in a standard format makes biomarkers more valuable because it allows for comparisons between studies.

Tumor mutation burden can be used not only as a diagnosis but also as a tool for monitoring a tumor throughout treatment, allowing physicians to identify and adapt to new mutations. We’re not there yet, but this could be the future of precision oncology.

The tumor mutation burden represents a significant step on the road to precision oncology and personalized medicine, but it is not the last. In the future, biomarkers will likely consist of multiple elements, including tumor mutation burden and other features such as inflammatory gene expression.