Visualization of the Effect of Assay Size on the Error Profile of Tumor Mutational Burden Measurement

• Published in: Genes Vol. 13; no. 3; p. 432
• Main Author: Bailey, Nathanael G
• Format: Journal Article
• Language: English
• Published: Switzerland MDPI AG 26.02.2022; MDPI
• Subjects: Biomarkers, Tumor - genetics; Confidence intervals; Histology; Humans; Immune Checkpoint Inhibitors; Kidney cancer; Laboratories; Melanoma; Mutation; Neoplasms - genetics; Neoplasms - pathology; precision medicine; Probability; tumor mutation burden; Tumors; tumor mutation burden; precision medicine; immune checkpoint inhibitors
• ISSN: 2073-4425; 2073-4425
• DOI: 10.3390/genes13030432

Tumor mutational burden (TMB) refers to the number of somatic mutations in a tumor per megabase and is a biomarker for response to immune checkpoint inhibitor therapy. Immune checkpoint inhibitors are currently approved for tumors with TMB greater than or equal to 10 mutations/megabase. Many laboratories are currently reporting TMB values based upon targeted resequencing panels with limited genomic coverage. Due to sampling variation, this leads to significant uncertainty in the assay's TMB result, particularly at relatively low TMB levels near the 10 mutation per megabase therapeutic threshold. In order to allow clinicians and laboratorians to explore this uncertainty, we built a novel web application that allows a user to view the potential error of a TMB result given the sequencing panel size. This application also allows the user to explore the effect of incorporating knowledge of a specific tumor type's typical TMB distribution on the error profile of the TMB result.