Tumor Mutational Burden (TMB) analysis across multiple genomic platforms with considerations for sample type utility and effects on numerical representation

Why Tumor Mutational Burden (TMB)?

Authors: Victor Weigman, Ph.D. and Stephanie Hastings, Ph.D.

In this presentation, you will learn about the impact of various molecular endpoints for facilitating therapeutic selection with considerations to the
patient’s immune response.   Determining the tumor mutational burden (TMB) has increased in adoption as a biomarker but how it is determined and the implications on interpretation are not standardized. We outline conventions for TMB calculation and suggest algorithm approaches and effects across matched samples tested with Exome, targeted panels, independent of normal samples.  Using colorectal cancer specimens, we demonstrate utility for extending traditional biomarker testing of FFPE into liquid biopsy inclusive of TMB calculation. We also review updates enhancing algorithms calling TMB with tumor tissue only, showing high linearity concordance to paired calls with high reproducibility and RNA-Sequencing, which are novel frontiers in this space and can extend advantage of TMB in datasets and specimens.