Abstract
Immunotherapies based on immune checkpoint inhibitors are emerging as an innovative treatment for different types of advanced cancers. While the utility of immune checkpoint inhibitors has been clearly demonstrated, the response rate is highly variable across individuals. Due to the cost and toxicity of these immunotherapies, a critical challenge in this field is the identification of predictive biomarkers to discriminate which patients may respond to immunotherapy. Recently, a high tumor mutational burden (TMB) has been identified as a genetic signature that is associated with a favorable outcome for immune checkpoint inhibitor therapy. The TMB is defined as the total number of nonsynonymous mutations per coding area of a tumor genome. Initially, it was determined using whole exome sequencing, but due to the high costs and long turnaround time of this method, targeted panel sequencing is currently being explored to measure TMB. In the near future, TMB evaluation may play an important role in immuno-oncology, but its implementation in a routine setting involves robust analytical and clinical validation. Standardization is also needed in order to make informed decisions about patients. This review presents the methodologies employed for determining TMB and discusses the factors that may have an impact on its measurement.
Keywords: Tumor mutational burden (TMB), whole-exome sequencing (WES), gene panels, methods
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6249625/
Methods of measurement for tumor mutational burden in tumor tissue
Re: Methods of measurement for tumor mutational burden in tumor tissue
Conclusions
As already underlined by others authors, evaluation of the TMB may play an important role in immuno-oncology (26). However, implementation of this test in a routine setting is still challenging. Sample size and DNA amount, varying testing platforms, varying bioinformatic pipelines, cut-off definition and costs are factors that potentially limit the implementation of the TMB evaluation. Moreover, standardizing the method of TMB measurement is needed in order to ensure reliability, reproducibility and clinical utility.
As already underlined by others authors, evaluation of the TMB may play an important role in immuno-oncology (26). However, implementation of this test in a routine setting is still challenging. Sample size and DNA amount, varying testing platforms, varying bioinformatic pipelines, cut-off definition and costs are factors that potentially limit the implementation of the TMB evaluation. Moreover, standardizing the method of TMB measurement is needed in order to ensure reliability, reproducibility and clinical utility.
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