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Thun, G.A.* ; Derdak, S.* ; Castro-Giner, F.* ; Apunte-Ramos, K.* ; Águeda, L.* ; Wjst, M. ; Boland, A.* ; Deleuze, J.F.* ; Kolsum, U.* ; Heiss-Neumann, M.S.* ; Nowinski, A.* ; Gorecka, D.* ; Hohlfeld, J.M.* ; Welte, T.* ; Brightling, C.E.* ; Parr, D.G.* ; Prasse, A.* ; Müller-Quernheim, J.* ; Greulich, T.* ; Stendardo, M.* ; Boschetto, P.* ; Barta, I.* ; Döme, B.* ; Gut, M.* ; Singh, D.* ; Ziegler-Heitbrock, L.* ; Gut, I.G.*

High degree of polyclonality hinders somatic mutation calling in lung brush samples of COPD cases and controls.

Sci. Rep. 9:20158 (2019)
Verlagsversion Forschungsdaten DOI PMC
Open Access Gold
Creative Commons Lizenzvertrag
Chronic obstructive pulmonary disease (COPD) is induced by cigarette smoking and characterized by inflammation of airway tissue. Since smokers with COPD have a higher risk of developing lung cancer than those without, we hypothesized that they carry more mutations in affected tissue. We called somatic mutations in airway brush samples from medium-coverage whole genome sequencing data from healthy never and ex-smokers (n = 8), as well as from ex-smokers with variable degrees of COPD (n = 4). Owing to the limited concordance of resulting calls between the applied tools we built a consensus, a strategy that was validated with high accuracy for cancer data. However, consensus calls showed little promise of representing true positives due to low mappability of corresponding sequence reads and high overlap with positions harbouring known genetic polymorphisms. A targeted re-sequencing approach suggested that only few mutations would survive stringent verification testing and that our data did not allow the inference of any difference in the mutational load of bronchial brush samples between former smoking COPD cases and controls. High polyclonality in airway brush samples renders medium-depth sequencing insufficient to provide the resolution to detect somatic mutations. Deep sequencing data of airway biopsies are needed to tackle the question.
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Publikationstyp Artikel: Journalartikel
Dokumenttyp Wissenschaftlicher Artikel
Schlagwörter Adult Stem-cells; Cancer-risk; Tissues; Genome; Signatures; Smoking; Number; Accumulation; Pathogenesis; Mechanisms
ISSN (print) / ISBN 2045-2322
e-ISSN 2045-2322
Zeitschrift Scientific Reports
Quellenangaben Band: 9, Heft: 1, Seiten: , Artikelnummer: 20158 Supplement: ,
Verlag Nature Publishing Group
Verlagsort London
Begutachtungsstatus