Koenig, Katharina, Peifer, Martin ORCID: 0000-0002-5243-5503, Fassunke, Jana, Ihle, Michaela A., Kuenstlinger, Helen, Heydt, Carina, Stamm, Katrin, Ueckeroth, Frank, Vollbrecht, Claudia ORCID: 0000-0002-0861-001X, Bos, Marc, Gardizi, Masyar, Scheffler, Matthias ORCID: 0000-0002-9031-1368, Nogova, Lucia, Leenders, Frauke, Albus, Kerstin, Meder, Lydia ORCID: 0000-0002-9547-5812, Becker, Kerstin, Florin, Alexandra, Rommerscheidt-Fuss, Ursula, Altmueller, Janine, Kloth, Michael, Nuernberg, Peter, Henkel, Thomas, Bikar, Sven-Ernoe, Sos, Martin L., Geese, William J., Strauss, Lewis, Ko, Yon-Dschun, Gerigk, Ulrich, Odenthal, Margarete, Zander, Thomas, Wolf, Juergen, Merkelbach-Bruse, Sabine, Buettner, Reinhard and Heukamp, Lukas C. (2015). Implementation of Amplicon Parallel Sequencing Leads to Improvement of Diagnosis and Therapy of Lung Cancer Patients. J. Thorac. Oncol., 10 (7). S. 1049 - 1058. NEW YORK: ELSEVIER SCIENCE INC. ISSN 1556-1380

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Abstract

Introduction: The Network Genomic Medicine Lung Cancer was set up to rapidly translate scientific advances into early clinical trials of targeted therapies in lung cancer performing molecular analyses of more than 3500 patients annually. Because sequential analysis of the relevant driver mutations on fixated samples is challenging in terms of workload, tissue availability, and cost, we established multiplex parallel sequencing in routine diagnostics. The aim was to analyze all therapeutically relevant mutations in lung cancer samples in a high-throughput fashion while significantly reducing turnaround time and amount of input DNA compared with conventional dideoxy sequencing of single polymerase chain reaction amplicons. Methods: In this study, we demonstrate the feasibility of a 102 amplicon multiplex polymerase chain reaction followed by sequencing on an Illumina sequencer on formalin-fixed paraffin-embedded tissue in routine diagnostics. Analysis of a validation cohort of 180 samples showed this approach to require significantly less input material and to be more reliable, robust, and cost-effective than conventional dideoxy sequencing. Subsequently, 2657 lung cancer patients were analyzed. Results: We observed that comprehensive biomarker testing provided novel information in addition to histological diagnosis and clinical staging. In 2657 consecutively analyzed lung cancer samples, we identified driver mutations at the expected prevalence. Furthermore we found potentially targetable DDR2 mutations at a frequency of 3% in both adenocarcinomas and squamous cell carcinomas. Conclusion: Overall, our data demonstrate the utility of systematic sequencing analysis in a clinical routine setting and highlight the dramatic impact of such an approach on the availability of therapeutic strategies for the targeted treatment of individual cancer patients.

Item Type: Journal Article
Creators:
CreatorsEmailORCIDORCID Put Code
Koenig, KatharinaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Peifer, MartinUNSPECIFIEDorcid.org/0000-0002-5243-5503UNSPECIFIED
Fassunke, JanaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Ihle, Michaela A.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Kuenstlinger, HelenUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Heydt, CarinaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Stamm, KatrinUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Ueckeroth, FrankUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Vollbrecht, ClaudiaUNSPECIFIEDorcid.org/0000-0002-0861-001XUNSPECIFIED
Bos, MarcUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Gardizi, MasyarUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Scheffler, MatthiasUNSPECIFIEDorcid.org/0000-0002-9031-1368UNSPECIFIED
Nogova, LuciaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Leenders, FraukeUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Albus, KerstinUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Meder, LydiaUNSPECIFIEDorcid.org/0000-0002-9547-5812UNSPECIFIED
Becker, KerstinUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Florin, AlexandraUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Rommerscheidt-Fuss, UrsulaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Altmueller, JanineUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Kloth, MichaelUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Nuernberg, PeterUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Henkel, ThomasUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Bikar, Sven-ErnoeUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Sos, Martin L.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Geese, William J.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Strauss, LewisUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Ko, Yon-DschunUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Gerigk, UlrichUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Odenthal, MargareteUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Zander, ThomasUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Wolf, JuergenUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Merkelbach-Bruse, SabineUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Buettner, ReinhardUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Heukamp, Lukas C.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
URN: urn:nbn:de:hbz:38-400453
DOI: 10.1097/JTO.0000000000000570
Journal or Publication Title: J. Thorac. Oncol.
Volume: 10
Number: 7
Page Range: S. 1049 - 1058
Date: 2015
Publisher: ELSEVIER SCIENCE INC
Place of Publication: NEW YORK
ISSN: 1556-1380
Language: English
Faculty: Unspecified
Divisions: Unspecified
Subjects: no entry
Uncontrolled Keywords:
KeywordsLanguage
FACTOR RECEPTOR MUTATIONS; KINASE INHIBITION; DRIVER MUTATIONS; CLASSIFICATION; IDENTIFICATION; RESISTANCE; IDENTIFY; PIK3CA; MAPK; GENEMultiple languages
Oncology; Respiratory SystemMultiple languages
URI: http://kups.ub.uni-koeln.de/id/eprint/40045

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