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

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 laborat...

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Detalles Bibliográficos
Autor principal: Bailey, Nathanael G.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8949329/
https://www.ncbi.nlm.nih.gov/pubmed/35327986
http://dx.doi.org/10.3390/genes13030432
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author Bailey, Nathanael G.
author_facet Bailey, Nathanael G.
author_sort Bailey, Nathanael G.
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description 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.
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spelling pubmed-89493292022-03-26 Visualization of the Effect of Assay Size on the Error Profile of Tumor Mutational Burden Measurement Bailey, Nathanael G. Genes (Basel) Article 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. MDPI 2022-02-26 /pmc/articles/PMC8949329/ /pubmed/35327986 http://dx.doi.org/10.3390/genes13030432 Text en © 2022 by the author. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Bailey, Nathanael G.
Visualization of the Effect of Assay Size on the Error Profile of Tumor Mutational Burden Measurement
title Visualization of the Effect of Assay Size on the Error Profile of Tumor Mutational Burden Measurement
title_full Visualization of the Effect of Assay Size on the Error Profile of Tumor Mutational Burden Measurement
title_fullStr Visualization of the Effect of Assay Size on the Error Profile of Tumor Mutational Burden Measurement
title_full_unstemmed Visualization of the Effect of Assay Size on the Error Profile of Tumor Mutational Burden Measurement
title_short Visualization of the Effect of Assay Size on the Error Profile of Tumor Mutational Burden Measurement
title_sort visualization of the effect of assay size on the error profile of tumor mutational burden measurement
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8949329/
https://www.ncbi.nlm.nih.gov/pubmed/35327986
http://dx.doi.org/10.3390/genes13030432
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