Tumor mutational burden: Difference between revisions

Latest revision as of 04:17, 18 February 2025

Overview of Tumor Mutational Burden (TMB)

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[edit]

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[edit]

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[edit]

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.

Clinical Significance[edit]

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[edit]

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.

Research and Developments[edit]

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[edit]

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[edit]

References[edit]

TMB Antigen Association
TMB All Samples
Factors Influencing TMB Calculation

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-'''Tumor Mutational Burden''' ('''TMB''') is a measure of the number of mutations carried by tumor cells. It is a potential biomarker of immunotherapy response, particularly in the context of [[checkpoint inhibitor]] therapies.
+{{Short description|Overview of Tumor Mutational Burden (TMB)}}
+{{Use dmy dates|date=October 2023}}
-==Definition==
+'''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.
-Tumor Mutational Burden is defined as the total number of non-synonymous mutations per megabase of genome examined. Non-synonymous mutations are those that result in a change in the amino acid sequence of the encoded protein. TMB is typically measured using [[Next-Generation Sequencing]] (NGS) technologies, which can detect both single nucleotide variants and small insertions and deletions.
+==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.
+[[File:Factors_influencing_TMB_Calculation.png|thumb|Factors influencing TMB calculation]]
 ==Clinical Significance==
-High TMB has been associated with a better response to immunotherapy in several types of cancer, including [[non-small cell lung cancer]] (NSCLC), [[melanoma]], and [[urothelial carcinoma]]. The rationale behind this is that a higher number of mutations leads to a greater number of [[neoantigens]], which are more likely to be recognized by the immune system as foreign, thus triggering an immune response.
+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.
-However, the relationship between TMB and immunotherapy response is not straightforward. Some tumors with low TMB also respond to immunotherapy, and not all tumors with high TMB respond. Therefore, TMB is currently considered as one of several potential biomarkers for immunotherapy response, alongside [[PD-L1]] expression and [[microsatellite instability]] (MSI).
+===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.
-==Measurement==
+[[File:TMB-Antigen_Association.jpg|thumb|TMB and antigen association]]
-TMB is typically measured using Next-Generation Sequencing (NGS) technologies. The most common method is [[whole exome sequencing]] (WES), which sequences the entire coding region of the genome. However, due to the high cost and complexity of WES, targeted gene panels that sequence a subset of the genome are often used in the clinical setting. These panels must be carefully designed to ensure they accurately capture TMB.
-==Limitations==
+==Research and Developments==
-There are several limitations to the use of TMB as a biomarker. First, there is currently no standardized method for measuring TMB, leading to variability between different labs. Second, TMB is a static measure that does not capture the dynamic nature of the tumor genome. Finally, TMB does not provide information on the specific mutations present in the tumor, some of which may have direct therapeutic implications.
+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.
-==See Also==
+==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)]]
-* [[Next-Generation Sequencing]]
+* [[Genomics]]
-* [[Neoantigen]]
-* [[Microsatellite instability]]
+==References==
+{{Reflist}}
+[[File:Tmb_all_samples.png|thumb|TMB across different samples]]
 [[Category:Oncology]]
-[[Category:Immunotherapy]]
 [[Category:Genomics]]
-{{Medicine-stub}}
+<gallery>
+File:TMB-Antigen_Association.jpg|TMB Antigen Association
+File:Tmb_all_samples.png|TMB All Samples
+File:Factors_influencing_TMB_Calculation.png|Factors Influencing TMB Calculation
+</gallery>