Tumor mutation burden (TMB) is the number of somatic mutations in the coding region of the tumor genome. It is an emerging biomarker that is related to the response to immunotherapeutics. Recent studies have shown that a high tumor mutation burden or burden increases the likelihood that immunogenic neoantigens expressed by tumor cells may induce a response to immunotherapy.
Next-generation sequencing (NGS) can help researchers estimate TMB, identify new antigens, study innovative therapies to enhance the immune response, and understand how genetic variation affects its efficacy. The characterization of expressed neoantigens will also facilitate the development of vaccines and cell-based therapies.
Estimated tumor mutation burden
Despite defining the clinical use of the tumor mutation burden, efforts are continuing to standardize TMB analysis.
New antigen identification
Mutations in the protein-coding genes of cancer cells are a source of potential new antigens that the immune system can target. NGS can predictively select novel tumor antigens that can be used to elicit tumor-specific responses. DNA and / or RNA can be effectively characterized by exome sequencing and / or transcriptome sequencing.
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2. Snyder A, Makarov V, Merghoub T, et al. Genetic Basis for Clinical Response to CTLA-4 Blockade in Melanoma. N Engl J Med. 2014.
3. Garofalo A, Sholl L, Reardon B, et al. The impact of tumor profiling approaches and genomic data strategies for cancer precision medicine. Genome Med. 2016.
4. Buchhalter I, Rempel E, Endris V, et al. Size Matters: Dissecting Key Parameters for Panel-Based Tumor Mutational Burden (TMB) Analysis. Int J Cancer. 2018.