Universität zu Köln

Heydt, Carina, Rehker, Jan, Pappesch, Roberto, Buhl, Theresa, Ball, Markus, Siebolts, Udo, Haak, Anja, Lohneis, Philipp, Buettner, Reinhard, Hillmer, Axel M. and Merkelbach-Bruse, Sabine (2020). Analysis of tumor mutational burden: correlation of five large gene panels with whole exome sequencing. Sci Rep, 10 (1). LONDON: NATURE PUBLISHING GROUP. ISSN 2045-2322

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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.

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code Heydt, Carina UNSPECIFIED UNSPECIFIED UNSPECIFIED Rehker, Jan UNSPECIFIED UNSPECIFIED UNSPECIFIED Pappesch, Roberto UNSPECIFIED UNSPECIFIED UNSPECIFIED Buhl, Theresa UNSPECIFIED UNSPECIFIED UNSPECIFIED Ball, Markus UNSPECIFIED UNSPECIFIED UNSPECIFIED Siebolts, Udo UNSPECIFIED UNSPECIFIED UNSPECIFIED Haak, Anja UNSPECIFIED UNSPECIFIED UNSPECIFIED Lohneis, Philipp UNSPECIFIED UNSPECIFIED UNSPECIFIED Buettner, Reinhard UNSPECIFIED UNSPECIFIED UNSPECIFIED Hillmer, Axel M. UNSPECIFIED UNSPECIFIED UNSPECIFIED Merkelbach-Bruse, Sabine UNSPECIFIED UNSPECIFIED UNSPECIFIED
URN:	urn:nbn:de:hbz:38-326659
DOI:	10.1038/s41598-020-68394-4
Journal or Publication Title:	Sci Rep
Volume:	10
Number:	1
Date:	2020
Publisher:	NATURE PUBLISHING GROUP
Place of Publication:	LONDON
ISSN:	2045-2322
Language:	English
Faculty:	Unspecified
Divisions:	Unspecified
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language BLOCKADE; DNA; STRATEGIES; NIVOLUMAB; ALIGNMENT; GENOME Multiple languages Multidisciplinary Sciences Multiple languages
URI:	http://kups.ub.uni-koeln.de/id/eprint/32665