Validating comprehensive next- generation sequencing results for precision oncology: The NCT/DKTK molecularly aided stratification for tumor eradication research experience

Amelie Lier, Roland Penzel, Christoph Heining, Peter Horak, Martina Fröhlich, Sebastian Uhrig, Jan Budczies, Martina Kirchner, Anna Lena Volckmar, Barbara Hutter, Simon Kreutzfeldt, Volker Endris, Daniela Richter, Stephan Wolf, Katrin Pfütze, Olaf Neumann, Ivo Buchhalter, Cristiano M.Morais de Oliveira, Stephan Singer, Jonas LeichsenringEsther Herpel, Frederick Klauschen, Philipp J. Jost, Klaus H. Metzeler, Klaus Schulze-Osthoff, Hans Georg Kopp, Thomas Kindler, Damian T. Rieke, Mario Lamping, Christian Brandts, Johanna Falkenhorst, Sebastian Bauer, Evelin Schröck, Gunnar Folprecht, Melanie Boerries, Nikolas von Bubnoff, Wilko Weichert, Benedikt Brors, Peter Lichter, Christof von Kalle, Peter Schirmacher, Hanno Glimm, Stefan Fröhling, Albrecht Stenzinger*

*Corresponding author for this work
6 Citations (Scopus)


Purpose Rapidly evolving genomics technologies, in particular comprehensive nextgeneration sequencing (NGS), have led to exponential growth in the understanding of cancer biology, shifting oncology toward personalized treatment strategies. However, comprehensive NGS approaches, such as whole-exome sequencing, have limitations that are related to the technology itself as well as to the input source. Hence, clinical implementation of comprehensive NGS in a quality-controlled diagnostic workflow requires both the standardization of sequencing procedures and continuous validation of sequencing results by orthogonal methods in an ongoing program to enable the determination of key test parameters and continuous improvement of NGS and bioinformatics pipelines. Patients and Methods We present validation data on 220 patients who were enrolled between 2013 and 2016 in a multi-institutional, genomics-guided precision oncology program (Molecularly Aided Stratification for Tumor Eradication Research) of the National Center for Tumor Diseases Heidelberg and the German Cancer Consortium. Results More than 90% of clinically actionable genomic alterations identified by combined whole-exome sequencing and transcriptome sequencing were successfully validated, with varying frequencies of discordant results across different types of alterations (fusions, 3.7%; single-nucleotide variants, 2.6%; amplifications, 1.1%; overexpression, 0.9%; deletions, 0.6%). The implementation of new computational methods for NGS data analysis led to a substantial improvement of gene fusion calling over time. Conclusion Collectively, these data demonstrate the value of a rigorous validation program that partners with comprehensive NGS to successfully implement and continuously improve cancer precision medicine in a clinical setting.

Original languageEnglish
JournalJCO Precision Oncology
Publication statusPublished - 2018


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