Innovative therapies have been developed to boost the immune response, such as checkpoint inhibitors, vaccines, and adoptive cell transfer. NGS applications have been helpful in developing these therapies and understanding how genetic variation can influence their efficacy.
Recent studies indicate that a high mutation load increases the likelihood that immunogenic neoantigens expressed by tumor cells may induce a response to immunotherapy.1-4 A more refined characterization of expressed neoantigens has also contributed to development of vaccines and cell-based therapeutic methods.
Tumor mutational burden or TMB, the number of mutations within the coding region of a tumor genome, is an emerging biomarker that correlates with response to immunotherapeutic agents such as checkpoint inhibitors.1-4 While the clinical utility of tumor mutational burden is being defined, continuing efforts to standardize TMB analysis are ongoing.
Recent studies have demonstrated that tumor mutational burden can be effectively estimated using targeted sequencing panels.5-6 Specific features are recommended to enhance accuracy in TMB scoring, such as a minimum size of 1.5 Mb genomic content, and algorithms to filter variants that are unlikely to contribute to immunogenicity. 5-6
Mutations in protein coding genes of cancer cells are a source of potential neoantigens that the immune system can target. NGS has enabled the predictive selection of novel tumor antigens that can be applied to elicit a tumor-specific response. DNA and/or RNA is efficiently characterized by exome sequencing and/or transcriptome sequencing, and improved bioinformatics tools aid neoantigen selection by predicting the presentation of mutant peptides for recognition by the immune system.
A study by Dr. Albrecht Stenzinger and his colleagues investigated the influence of gene panel size on the precision of tumor mutational burden measurement. Their findings were recently published in the International Journal of Cancer.Read Article
Illumina offers several library preparation and sequencing options with access to data analysis options for tumor mutational load and neoantigen analysis. Streamlined workflows and flexible kit configurations accommodate multiple study designs.
Approximately 90% of the world’s sequencing data are generated using Illumina sequencing by synthesis (SBS) chemistry.*
Click on the below to view products for each workflow step.
The TruSeq RNA Exome library prep kit provides a low-cost solution for analyzing human RNA isolated from limited or low-quality samples, including FFPE.TruSeq DNA Exome
TruSeq DNA Exome is a cost-effective library preparation and exome enrichment solution.TruSeq Stranded Total RNA Library Prep Kit
A robust, highly scalable whole-transcriptome analysis solution for a variety of species and sample types, including FFPE.
Assay targeting multiple variant types, including tumor mutational burden (TMB) and microsatellite instability (MSI), even from low-quality samples.
*Data calculations on file, Illumina, Inc, 2017.