Authors: Victor Weigman & Natalie Mola
Tumor mutational burden (TMB), a measure of the number of somatic mutations per Mb of the assay target region, is becoming a common biomarker in prediction of immunotherapy response. As the tumor evolves, mutations are accumulated, leading to growth advantages and opportunities for presentation of new neoantigens. Immunotherapies designed to antagonize common checkpoint inhibitors like PD1/PD-L1 and CTLA4 correct for this immune evasion and mutational burden provides a continuous variable that’s prognostic to this attainment. This is also showing promise in second and third line inhibitory compounds (TIM-3, LAG3, IDO1) and co-stimulatory antibodies (OX40, GITR, CD40).
Calculation of TMB is dependent on calling tumor-derived (somatic) mutations that are derived from identifying variants in the tumor cells and contrasting them against variants in a matched normal/germline sample. However, this approach increases costs of testing and in many cases, may not be possible if a normal sample cannot be obtained, consented or absent from a clinical trial protocol for TMB testing. To increase applicability of TMB to the volume of retrospective studies, calculation must be able to be performed by using only the tumor specimen and we feel our approach provides robust calculation across use cases.
Download our poster from SITC 2018 to learn more about our tumor-only TMB pipeline, using somatic classifications determined using a random forest model.
Complete the form below to access this scientific poster
Related Insights
Reproducibility Challenges in an era of Massive Data
Presented at the MCBIOS & MAQC 2021 Joint Conference
A Verified Genomic Reference Sample for Assessing Performance of Cancer Panels Detecting Small Variants of Low Allele Frequency
Presented at the MCBIOS & MAQC 2021 Joint Conference
Unexpected Impacts to Library Complexity After DNA and RNA Library Preparation in Illumina Next Generation Sequencing
Presented at the MCBIOS & MAQC 2021 Joint Conference
Immune Landscape Signatures for Characterization of Tumor Microenvironment and Response to Therapy
Gene expression and analysis for detection of 38 Immune Landscape Signatures
Using Gene Signature Methodologies to Strengthen Immuno-Oncology Trials
Genomic technologies that empower and enhance immuno-oncology trials
Laboratory Solutions for Hepatitis B (HBV) Clinical Trials
Insight brief by Joseph Sebastian, Ph.D., Scientific Advisor, Infectious & Liver Diseases
Enabling blood sample prep for single cell sequencing in clinical research
The Role of Genomics in Clinical Trials with Patrick Hurban
I-O clinical development podcast series
IQVIA Laboratories Corporate Brochure
A global drug discovery and development laboratory services organization
Evaluating and Implementing SARS-CoV-2 PCR Tests for Diagnostic and Clinical Trial Use
AAPS 2020 COVID-19 Workshop: Current Pharmaceutical Developments for Cures and Prevention
