Tumor mutational burden (TMB) is the number of somatic mutations within the coding region of a tumor genome. It correlates with response to immunotherapeutic agents such as checkpoint inhibitors.1-5 Studies have indicated that a high tumor mutational burden, or load, increases the likelihood that immunogenic neoantigens expressed by tumor cells may induce a response to immunotherapy.1-4
Numerous clinical studies have demonstrated that higher mutational burden correlates to improved survival benefits in patients receiving checkpoint inhibitor therapies for cancers such as melanoma, colon, and non-small cell lung cancer (NSCLC). Data from past clinical trials like CheckMate 227 have demonstrated that, in NSCLC, higher TMB is associated with improved clinical outcomes.6
13-26% of advanced cancer patients exhibit TMB-High results across tumor types.5,7-10
Large assays with ~1.1 Mb of coding genome are needed to accurately assess TMB.11, 12 Comprehensive Genomic Profiling (CGP) analyzes hundreds of biomarkers simultaneously, including TMB.
TMB measured from blood (bTMB) using CGP has been associated with improved clinical outcomes when ≥ 20 mutations per megabase were detected in mNSCLC.13-15
Clinical trials and regulatory approvals have established several cancer immunotherapy treatments for multiple tumor types.16 The ability to identify molecular signatures that help predict response to these treatments is important for better predicting who will benefit from these treatments.
Tumor mutational burden (TMB) and microsatellite instability (MSI) status are two FDA-approved biomarkers indicative of patient response to immunotherapy and recommended for testing by guidelines.17-18
Comprehensive genomic profiling (CGP) can detect biomarkers at nucleotide-level resolution and typically comprises all large genomic signatures (TMB, MSI), maximizing the ability to find clinically actionable alterations.
Single-gene and small hotspot panel testing methods are not large enough to detect known and emerging biomarkers and molecular signatures, potentially missing important actionable variants.19-22 CGP provides broad molecular coverage of the genome, capturing a comprehensive set of clinically relevant genes in one test.
CGP can offer both actionable and potentially actionable results to help identify more effective therapeutic paths and innovative clinical trial options for cancer patients.Learn more about CGP
TruSight Oncology Comprehensive (EU) is the first CE-marked IVD test kit for comprehensive genomic profiling based on DNA and RNA that consolidates multiple iterative tests into one.
The NextSeq 550Dx instrument is a CE-marked IVD that enables clinical laboratories to develop and perform a wide range of applications..
Analyze results using the TruSight Oncology Comprehensive Local Run Manager analysis module.
A study by Dr. Albrecht Stenzinger and his colleagues investigated the influence of gene panel size on the precision of tumor mutational burden measurement.