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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doaj-9ffba0af5f5c4416968c0b58a4842a722021-07-11T11:24:45ZengNature Publishing GroupScientific Reports2045-23222020-07-0110111010.1038/s41598-020-68394-4Analysis of tumor mutational burden: correlation of five large gene panels with whole exome sequencingCarina Heydt0Jan Rehker1Roberto Pappesch2Theresa Buhl3Markus Ball4Udo Siebolts5Anja Haak6Philipp Lohneis7Reinhard Büttner8Axel M. Hillmer9Sabine Merkelbach-Bruse10Institute of Pathology, Faculty of Medicine, University of CologneInstitute of Pathology, Faculty of Medicine, University of CologneInstitute of Pathology, Faculty of Medicine, University of CologneInstitute of Pathology, Faculty of Medicine, University of CologneInstitute of Pathology, Faculty of Medicine, University of CologneInstitute of Pathology, University Hospital Halle (Saale)Institute of Pathology, University Hospital Halle (Saale)Institute of Pathology, Faculty of Medicine, University of CologneInstitute of Pathology, Faculty of Medicine, University of CologneInstitute of Pathology, Faculty of Medicine, University of CologneInstitute of Pathology, Faculty of Medicine, University of CologneAbstract 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.https://doi.org/10.1038/s41598-020-68394-4 |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
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 |
spellingShingle |
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 Scientific Reports |
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 Publishing Group |
series |
Scientific Reports |
issn |
2045-2322 |
publishDate |
2020-07-01 |
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. |
url |
https://doi.org/10.1038/s41598-020-68394-4 |
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