Universität zu Köln

Gassa, Asmae, Fassunke, Jana, Schueten, Sarah, Kuhlmann, Luca, Scherer, Marie, Qien, Jie, Zhao, Yue, Michel, Max, Loeser, Heike, Wolf, Juergen, Buettner, Reinhard, Doerr, Fabian, Heldwein, Matthias, Hagmeyer, Lars, Frank, Konrad, Merkelbach-Bruse, Sabine, Quaas, Alexander, Bruns, Christiane, Hekmat, Khosro, Weiss, Jonathan, Wahlers, Thorsten and Alakus, Hakan (2021). Detection of circulating tumor DNA by digital droplet PCR in resectable lung cancer as a predictive tool for recurrence. Lung Cancer, 151. S. 91 - 97. CLARE: ELSEVIER IRELAND LTD. ISSN 1872-8332

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Abstract

Lung cancer is the leading cause of cancer-related mortality worldwide due to difficulties in early detection and high postsurgical recurrence rate. Current European Guidelines recommend follow-up via computerized tomography (CT) scans on regular basis within the first 2 years after radical surgical resection. Despite these efforts, recurrence rates remain high with 30-70 %. Therefore, it is imperative to develop predictive markers for metastases and postsurgical recurrence using minimally invasive methods. This prospective study aims at defining the feasibility of detecting circulating tumor DNA (ctDNA) in presurgical plasma samples of patients with lung cancer by digital droplet PCR. Resected tumor tissue and simultaneous blood samples were collected from 24 patients with lung cancer in stage I-IIIA (12 stage I, 8 stage II, 4 stage III). Genomic DNA from the tumor tissue samples were analyzed for hotspot mutations using a 17 gene panel next-generation sequencing (NGS) assay. CtDNA from corresponding plasma samples were analyzed using digital droplet PCR (ddPCR). Additionally, DNA sequencing results were correlated with patients' outcome. At least one somatic mutation was detected by NGS (96 %) in 23 of the tested tissue samples. DdPCR detected mutations in circulating cell-free DNA (ccfDNA) of nine patients' samples (9/23, 39 %). Postsurgical outcome analysis was performed for those patients who had received complete tumor resection (n = 21). Four of them suffered from an early relapse within the first two years after surgery, including two with detectable somatic mutations in ccfDNA during primary staging. Taken together, we showed that the 17 gene panel assay revealed in 23 of 24 patients at least one somatic mutation in the primary tumor by NGS. Tumor-specific mutation was detectable in 39 % from the blood of early stage lung cancer patients by ddPCR.

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code Gassa, Asmae UNSPECIFIED UNSPECIFIED UNSPECIFIED Fassunke, Jana UNSPECIFIED UNSPECIFIED UNSPECIFIED Schueten, Sarah UNSPECIFIED UNSPECIFIED UNSPECIFIED Kuhlmann, Luca UNSPECIFIED UNSPECIFIED UNSPECIFIED Scherer, Marie UNSPECIFIED UNSPECIFIED UNSPECIFIED Qien, Jie UNSPECIFIED UNSPECIFIED UNSPECIFIED Zhao, Yue UNSPECIFIED UNSPECIFIED UNSPECIFIED Michel, Max UNSPECIFIED UNSPECIFIED UNSPECIFIED Loeser, Heike UNSPECIFIED UNSPECIFIED UNSPECIFIED Wolf, Juergen UNSPECIFIED UNSPECIFIED UNSPECIFIED Buettner, Reinhard UNSPECIFIED UNSPECIFIED UNSPECIFIED Doerr, Fabian UNSPECIFIED UNSPECIFIED UNSPECIFIED Heldwein, Matthias UNSPECIFIED UNSPECIFIED UNSPECIFIED Hagmeyer, Lars UNSPECIFIED UNSPECIFIED UNSPECIFIED Frank, Konrad UNSPECIFIED UNSPECIFIED UNSPECIFIED Merkelbach-Bruse, Sabine UNSPECIFIED UNSPECIFIED UNSPECIFIED Quaas, Alexander UNSPECIFIED UNSPECIFIED UNSPECIFIED Bruns, Christiane UNSPECIFIED UNSPECIFIED UNSPECIFIED Hekmat, Khosro UNSPECIFIED UNSPECIFIED UNSPECIFIED Weiss, Jonathan UNSPECIFIED UNSPECIFIED UNSPECIFIED Wahlers, Thorsten UNSPECIFIED UNSPECIFIED UNSPECIFIED Alakus, Hakan UNSPECIFIED UNSPECIFIED UNSPECIFIED
URN:	urn:nbn:de:hbz:38-565022
DOI:	10.1016/j.lungcan.2020.10.019
Journal or Publication Title:	Lung Cancer
Volume:	151
Page Range:	S. 91 - 97
Date:	2021
Publisher:	ELSEVIER IRELAND LTD
Place of Publication:	CLARE
ISSN:	1872-8332
Language:	English
Faculty:	Unspecified
Divisions:	Unspecified
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language EXPRESSION Multiple languages Oncology; Respiratory System Multiple languages
URI:	http://kups.ub.uni-koeln.de/id/eprint/56502