npj Precision Oncology (Oct 2023)
Multicentric pilot study to standardize clinical whole exome sequencing (WES) for cancer patients
- Michael Menzel,
- Stephan Ossowski,
- Sebastian Kral,
- Patrick Metzger,
- Peter Horak,
- Ralf Marienfeld,
- Melanie Boerries,
- Steffen Wolter,
- Markus Ball,
- Olaf Neumann,
- Sorin Armeanu-Ebinger,
- Christopher Schroeder,
- Uta Matysiak,
- Hannah Goldschmid,
- Vincent Schipperges,
- Axel Fürstberger,
- Michael Allgäuer,
- Timo Eberhardt,
- Jakob Niewöhner,
- Andreas Blaumeiser,
- Carolin Ploeger,
- Tobias Bernd Haack,
- Timothy Kwang Yong Tay,
- Olga Kelemen,
- Thomas Pauli,
- Martina Kirchner,
- Klaus Kluck,
- Alexander Ott,
- Marcus Renner,
- Jakob Admard,
- Axel Gschwind,
- Silke Lassmann,
- Hans Kestler,
- Falko Fend,
- Anna Lena Illert,
- Martin Werner,
- Peter Möller,
- Thomas Theodor Werner Seufferlein,
- Nisar Malek,
- Peter Schirmacher,
- Stefan Fröhling,
- Daniel Kazdal,
- Jan Budczies,
- Albrecht Stenzinger
Affiliations
- Michael Menzel
- Institute of Pathology, Heidelberg University Hospital
- Stephan Ossowski
- Institute of Medical Genetics and Applied Genomics, University of Tübingen
- Sebastian Kral
- Institute for Surgical Pathology, Medical Center, University of Freiburg
- Patrick Metzger
- Center for Personalized Medicine (ZPM)
- Peter Horak
- Center for Personalized Medicine (ZPM)
- Ralf Marienfeld
- Institute of Pathology, University Hospital Ulm
- Melanie Boerries
- Center for Personalized Medicine (ZPM)
- Steffen Wolter
- Institute for Surgical Pathology, Medical Center, University of Freiburg
- Markus Ball
- Institute of Pathology, Heidelberg University Hospital
- Olaf Neumann
- Institute of Pathology, Heidelberg University Hospital
- Sorin Armeanu-Ebinger
- Institute of Medical Genetics and Applied Genomics, University of Tübingen
- Christopher Schroeder
- Institute of Medical Genetics and Applied Genomics, University of Tübingen
- Uta Matysiak
- Institute for Surgical Pathology, Medical Center, University of Freiburg
- Hannah Goldschmid
- Institute of Pathology, Heidelberg University Hospital
- Vincent Schipperges
- Center for Personalized Medicine (ZPM)
- Axel Fürstberger
- Institute of Pathology, University Hospital Ulm
- Michael Allgäuer
- Institute of Pathology, Heidelberg University Hospital
- Timo Eberhardt
- Institute of Pathology, University Hospital Ulm
- Jakob Niewöhner
- Institute of Pathology, University Hospital Ulm
- Andreas Blaumeiser
- Center for Personalized Medicine (ZPM)
- Carolin Ploeger
- Institute of Pathology, Heidelberg University Hospital
- Tobias Bernd Haack
- Institute of Medical Genetics and Applied Genomics, University of Tübingen
- Timothy Kwang Yong Tay
- Institute of Pathology, Heidelberg University Hospital
- Olga Kelemen
- Institute of Medical Genetics and Applied Genomics, University of Tübingen
- Thomas Pauli
- Center for Personalized Medicine (ZPM)
- Martina Kirchner
- Institute of Pathology, Heidelberg University Hospital
- Klaus Kluck
- Institute of Pathology, Heidelberg University Hospital
- Alexander Ott
- Institute of Medical Genetics and Applied Genomics, University of Tübingen
- Marcus Renner
- Institute of Pathology, Heidelberg University Hospital
- Jakob Admard
- Institute of Medical Genetics and Applied Genomics, University of Tübingen
- Axel Gschwind
- Institute of Medical Genetics and Applied Genomics, University of Tübingen
- Silke Lassmann
- Institute for Surgical Pathology, Medical Center, University of Freiburg
- Hans Kestler
- Institute of Pathology, University Hospital Ulm
- Falko Fend
- Institute of Pathology and Neuropathology, University Hospital Tübingen
- Anna Lena Illert
- Department of Medicine I, Medical Center-University of Freiburg, Faculty of Medicine, University of Freiburg
- Martin Werner
- Institute for Surgical Pathology, Medical Center, University of Freiburg
- Peter Möller
- Institute of Pathology, University Hospital Ulm
- Thomas Theodor Werner Seufferlein
- Center for Personalized Medicine (ZPM)
- Nisar Malek
- Center for Personalized Medicine (ZPM)
- Peter Schirmacher
- Institute of Pathology, Heidelberg University Hospital
- Stefan Fröhling
- Center for Personalized Medicine (ZPM)
- Daniel Kazdal
- Institute of Pathology, Heidelberg University Hospital
- Jan Budczies
- Institute of Pathology, Heidelberg University Hospital
- Albrecht Stenzinger
- Institute of Pathology, Heidelberg University Hospital
- DOI
- https://doi.org/10.1038/s41698-023-00457-x
- Journal volume & issue
-
Vol. 7,
no. 1
pp. 1 – 11
Abstract
Abstract A growing number of druggable targets and national initiatives for precision oncology necessitate broad genomic profiling for many cancer patients. Whole exome sequencing (WES) offers unbiased analysis of the entire coding sequence, segmentation-based detection of copy number alterations (CNAs), and accurate determination of complex biomarkers including tumor mutational burden (TMB), homologous recombination repair deficiency (HRD), and microsatellite instability (MSI). To assess the inter-institution variability of clinical WES, we performed a comparative pilot study between German Centers of Personalized Medicine (ZPMs) from five participating institutions. Tumor and matched normal DNA from 30 patients were analyzed using custom sequencing protocols and bioinformatic pipelines. Calling of somatic variants was highly concordant with a positive percentage agreement (PPA) between 91 and 95% and a positive predictive value (PPV) between 82 and 95% compared with a three-institution consensus and full agreement for 16 of 17 druggable targets. Explanations for deviations included low VAF or coverage, differing annotations, and different filter protocols. CNAs showed overall agreement in 76% for the genomic sequence with high wet-lab variability. Complex biomarkers correlated strongly between institutions (HRD: 0.79–1, TMB: 0.97–0.99) and all institutions agreed on microsatellite instability. This study will contribute to the development of quality control frameworks for comprehensive genomic profiling and sheds light onto parameters that require stringent standardization.
