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Related Experiment Video

Updated: Jan 19, 2026

Flow-sorting and Exome Sequencing of the Reed-Sternberg Cells of Classical Hodgkin Lymphoma

Flow-sorting and Exome Sequencing of the Reed-Sternberg Cells of Classical Hodgkin Lymphoma

Published on: June 10, 2017

Measuring Tumor Mutational Burden Using Whole-Exome Sequencing.

Tomas Vilimas¹

¹Molecular Characterization Laboratory, Frederick National Laboratory for Cancer Research, Leidos Biomedical Research, Inc., Frederick, MD, USA. tomas.vilimas@nih.gov.

Methods in Molecular Biology (Clifton, N.J.)

|September 11, 2019

Summary

Tumor mutational burden (TMB) is a key predictor of cancer immunotherapy response. Measuring TMB using whole-exome sequencing (WES) helps identify patients likely to benefit from immune checkpoint inhibitors (ICIs).

Keywords:

Cancer immunotherapy biomarker Immune checkpoint inhibitor Neoantigens Next-generation sequencing Nonsynonymous mutations Tumor mutational burden Whole-exome sequencing

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Last Updated: Jan 19, 2026

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Published on: June 10, 2017

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Published on: September 20, 2016

Detection of Rare Mutations in CtDNA Using Next Generation Sequencing

Detection of Rare Mutations in CtDNA Using Next Generation Sequencing

Published on: August 24, 2017

Area of Science:

Oncology
Immunology
Genomics

Background:

Cancer immunotherapy utilizing immune checkpoint inhibitors (ICIs) targeting CTLA-4 and PD-1/PD-L1 has shown significant success in various cancers.
Patient response to ICIs correlates with tumor mutational burden (TMB), a measure of single nucleotide variant (SNV) mutations within the tumor genome.

Purpose of the Study:

To present best-practice methods for measuring TMB in tumor specimens.
To highlight TMB as a predictive biomarker for ICI therapy efficacy.

Main Methods:

Whole-exome sequencing (WES) is employed for TMB measurement.
TMB is quantified as the number of nonsynonymous SNVs per megabase of the sequenced genome.

Main Results:

High TMB is associated with improved objective response and overall survival in patients treated with ICIs.
TMB predicts ICI response in melanoma, urothelial carcinoma, and a subset of non-small cell lung cancer (NSCLC) patients.

Conclusions:

TMB is a promising predictive biomarker for guiding ICI therapy selection.
Increased TMB leads to more neoantigens, enhancing T cell-mediated tumor cell killing and response to immunotherapy.