Analysis of tumor mutational burden: correlation of five large gene panels with whole exome sequencing

Abstract Outcome of immune checkpoint inhibition in cancer can be predicted by measuring PDL1 expression of tumor cells. Search for additional biomarkers led to tumor mutational burden (TMB) as surrogate marker for neoantigens presented. While TMB was previously determined via whole exome sequencing...

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Autores principales:	Carina Heydt, Jan Rehker, Roberto Pappesch, Theresa Buhl, Markus Ball, Udo Siebolts, Anja Haak, Philipp Lohneis, Reinhard Büttner, Axel M. Hillmer, Sabine Merkelbach-Bruse
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2020
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/9ffba0af5f5c4416968c0b58a4842a72
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spelling	oai:doaj.org-article:9ffba0af5f5c4416968c0b58a4842a722021-12-02T15:39:40ZAnalysis of tumor mutational burden: correlation of five large gene panels with whole exome sequencing10.1038/s41598-020-68394-42045-2322https://doaj.org/article/9ffba0af5f5c4416968c0b58a4842a722020-07-01T00:00:00Zhttps://doi.org/10.1038/s41598-020-68394-4https://doaj.org/toc/2045-2322Abstract Outcome of immune checkpoint inhibition in cancer can be predicted by measuring PDL1 expression of tumor cells. Search for additional biomarkers led to tumor mutational burden (TMB) as surrogate marker for neoantigens presented. While TMB was previously determined via whole exome sequencing (WES), there have been approaches with comprehensive gene panels as well. We sequenced samples derived from formalin-fixed tumors, a POLE mutated cell line and standard DNA by WES and five different panels. If available, normal tissue was also exome sequenced. Sequencing data was analyzed by commercial software solutions and an in-house pipeline. A robust Pearson correlation (R = 0.9801 ± 0.0167; mean ± sd; N = 7) was determined for the different panels in a tumor paired normal setting for WES. Expanded analysis on tumor only exome sequenced samples yielded similar correlation (R = 0.9439 ± 0.0632; mean ± sd; N = 14). Remaining germline variants increased TMB in WES by 5.761 ± 1.953 (mean ± sd.; N = 7) variants per megabase (v/mb) for samples including synonymous variants and 3.883 ± 1.38 v/mb for samples without synonymous variants compared to tumor-normal paired calling results. Due to limited sample numbers in this study, additional replication is suggested for a clinical setting. Remaining germline variants in a tumor-only setting and artifacts caused by different library chemistries construction might affect the results.Carina HeydtJan RehkerRoberto PappeschTheresa BuhlMarkus BallUdo SieboltsAnja HaakPhilipp LohneisReinhard BüttnerAxel M. HillmerSabine Merkelbach-BruseNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 10, Iss 1, Pp 1-10 (2020)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Carina Heydt Jan Rehker Roberto Pappesch Theresa Buhl Markus Ball Udo Siebolts Anja Haak Philipp Lohneis Reinhard Büttner Axel M. Hillmer Sabine Merkelbach-Bruse Analysis of tumor mutational burden: correlation of five large gene panels with whole exome sequencing
description	Abstract Outcome of immune checkpoint inhibition in cancer can be predicted by measuring PDL1 expression of tumor cells. Search for additional biomarkers led to tumor mutational burden (TMB) as surrogate marker for neoantigens presented. While TMB was previously determined via whole exome sequencing (WES), there have been approaches with comprehensive gene panels as well. We sequenced samples derived from formalin-fixed tumors, a POLE mutated cell line and standard DNA by WES and five different panels. If available, normal tissue was also exome sequenced. Sequencing data was analyzed by commercial software solutions and an in-house pipeline. A robust Pearson correlation (R = 0.9801 ± 0.0167; mean ± sd; N = 7) was determined for the different panels in a tumor paired normal setting for WES. Expanded analysis on tumor only exome sequenced samples yielded similar correlation (R = 0.9439 ± 0.0632; mean ± sd; N = 14). Remaining germline variants increased TMB in WES by 5.761 ± 1.953 (mean ± sd.; N = 7) variants per megabase (v/mb) for samples including synonymous variants and 3.883 ± 1.38 v/mb for samples without synonymous variants compared to tumor-normal paired calling results. Due to limited sample numbers in this study, additional replication is suggested for a clinical setting. Remaining germline variants in a tumor-only setting and artifacts caused by different library chemistries construction might affect the results.
format	article
author	Carina Heydt Jan Rehker Roberto Pappesch Theresa Buhl Markus Ball Udo Siebolts Anja Haak Philipp Lohneis Reinhard Büttner Axel M. Hillmer Sabine Merkelbach-Bruse
author_facet	Carina Heydt Jan Rehker Roberto Pappesch Theresa Buhl Markus Ball Udo Siebolts Anja Haak Philipp Lohneis Reinhard Büttner Axel M. Hillmer Sabine Merkelbach-Bruse
author_sort	Carina Heydt
title	Analysis of tumor mutational burden: correlation of five large gene panels with whole exome sequencing
title_short	Analysis of tumor mutational burden: correlation of five large gene panels with whole exome sequencing
title_full	Analysis of tumor mutational burden: correlation of five large gene panels with whole exome sequencing
title_fullStr	Analysis of tumor mutational burden: correlation of five large gene panels with whole exome sequencing
title_full_unstemmed	Analysis of tumor mutational burden: correlation of five large gene panels with whole exome sequencing
title_sort	analysis of tumor mutational burden: correlation of five large gene panels with whole exome sequencing
publisher	Nature Portfolio
publishDate	2020
url	https://doaj.org/article/9ffba0af5f5c4416968c0b58a4842a72
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Analysis of tumor mutational burden: correlation of five large gene panels with whole exome sequencing

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