Tumor mutational burden

Tumor Mutational Burden (TMB) is a measure of the number of mutations carried by tumor cells in a cancerous tissue. It is an emerging biomarker used in oncology to predict the response to immunotherapy treatments.

Overview

TMB is quantified by counting the number of somatic mutations per megabase (Mb) of the genome in a tumor sample. High TMB is often associated with a greater likelihood of response to immune checkpoint inhibitors, a class of drugs that help the immune system recognize and attack cancer cells.

Calculation

The calculation of TMB involves sequencing the DNA of tumor cells and identifying mutations. The total number of mutations is then divided by the size of the coding region of the genome that was sequenced, typically expressed in megabases.

Factors Influencing TMB Calculation

Several factors can influence the calculation of TMB, including the type of sequencing technology used, the depth of sequencing, and the bioinformatics pipeline employed to call mutations.

Factors influencing TMB calculation

Clinical Significance

TMB has been shown to correlate with the efficacy of immunotherapy in several types of cancer, including melanoma, non-small cell lung cancer, and bladder cancer. Patients with high TMB are more likely to benefit from treatments such as PD-1 and PD-L1 inhibitors.

TMB and Antigen Presentation

High TMB can lead to the production of more neoantigens, which are novel peptides presented on the surface of tumor cells. These neoantigens can be recognized by the immune system, potentially enhancing the effectiveness of immunotherapy.

TMB and antigen association

Research and Developments

Ongoing research is focused on standardizing TMB measurement and understanding its role in different cancer types. Studies are also exploring the combination of TMB with other biomarkers to improve the prediction of immunotherapy response.

Challenges

Despite its potential, TMB as a biomarker faces challenges, including variability in measurement techniques and the need for large-scale validation studies. Additionally, the cost and complexity of genomic sequencing can limit its widespread use in clinical practice.

Related Pages

• Cancer immunotherapy
• Biomarker (medicine)
• Genomics

References

TMB across different samples

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  TMB Antigen Association
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  TMB All Samples
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  Factors Influencing TMB Calculation