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

Autor: Thun GA; CNAG-CRG, Centre for Genomic Regulation (CRG), Barcelona Institute of Science and Technology (BIST), Barcelona, Spain., Derdak S; CNAG-CRG, Centre for Genomic Regulation (CRG), Barcelona Institute of Science and Technology (BIST), Barcelona, Spain., Castro-Giner F; CNAG-CRG, Centre for Genomic Regulation (CRG), Barcelona Institute of Science and Technology (BIST), Barcelona, Spain., Apunte-Ramos K; CNAG-CRG, Centre for Genomic Regulation (CRG), Barcelona Institute of Science and Technology (BIST), Barcelona, Spain., Águeda L; CNAG-CRG, Centre for Genomic Regulation (CRG), Barcelona Institute of Science and Technology (BIST), Barcelona, Spain., Wjst M; Helmholtz-Zentrum München, National Research Centre for Environmental Health, Institute of Lung Biology and Disease, Neuherberg, Germany.; Institute of Medical Statistics, Epidemiology and Medical Informatics, Technical University Munich, Munich, Germany., Boland A; Centre National de Recherche en Génomique Humaine (CNRGH), Institut de Biologie François Jacob, CEA, Université Paris-Saclay, Evry, France., Deleuze JF; Centre National de Recherche en Génomique Humaine (CNRGH), Institut de Biologie François Jacob, CEA, Université Paris-Saclay, Evry, France., Kolsum U; University of Manchester, Manchester University NHS Foundation Trust, Manchester, UK., Heiss-Neumann MS; EvA Study Center, Helmholtz-Zentrum München, Gauting, Germany., Nowinski A; 2nd Department of Respiratory Medicine, National Institute of Tuberculosis and Lung Diseases, Warsaw, Poland., Gorecka D; 2nd Department of Respiratory Medicine, National Institute of Tuberculosis and Lung Diseases, Warsaw, Poland., Hohlfeld JM; Fraunhofer Institute for Toxicology and Experimental Medicine, Member of the German Center of Lung Research, Hannover, Germany.; Department of Respiratory Medicine, Hannover Medical School, Member of the German Center of Lung Research, Hannover, Germany., Welte T; Department of Respiratory Medicine, Hannover Medical School, Member of the German Center of Lung Research, Hannover, Germany., Brightling CE; Department of Infection, Immunity and Inflammation, Institute for Lung Health, University of Leicester, Leicester, UK., Parr DG; Department of Respiratory Medicine, University Hospitals Coventry and Warwickshire NHS Trust, Coventry, UK., Prasse A; Department of Respiratory Medicine, Hannover Medical School, Member of the German Center of Lung Research, Hannover, Germany.; Department of Pneumology, University Medical Center, Freiburg, Germany., Müller-Quernheim J; Department of Pneumology, University Medical Center, Freiburg, Germany., Greulich T; Department of Medicine, Pulmonary and Critical Care Medicine, University Medical Center Giessen and Marburg, Philipps-University, Marburg, Germany., Stendardo M; Department of Medical Sciences, University of Ferrara and University-Hospital of Ferrara, Ferrara, Italy., Boschetto P; Department of Medical Sciences, University of Ferrara and University-Hospital of Ferrara, Ferrara, Italy., Barta I; Department of Pathophysiology, National Koranyi Institute for Pulmonology, Budapest, Hungary., Döme B; Department of Tumorbiology, National Koranyi Institute for Pulmonology, Budapest, Hungary., Gut M; CNAG-CRG, Centre for Genomic Regulation (CRG), Barcelona Institute of Science and Technology (BIST), Barcelona, Spain.; Universitat Pompeu Fabra, Barcelona, Spain., Singh D; University of Manchester, Manchester University NHS Foundation Trust, Manchester, UK., Ziegler-Heitbrock L; EvA Study Center, Helmholtz-Zentrum München, Gauting, Germany., Gut IG; CNAG-CRG, Centre for Genomic Regulation (CRG), Barcelona Institute of Science and Technology (BIST), Barcelona, Spain. ivo.gut@cnag.crg.eu.; Universitat Pompeu Fabra, Barcelona, Spain. ivo.gut@cnag.crg.eu.
Jazyk: angličtina
Zdroj: Scientific reports [Sci Rep] 2019 Dec 27; Vol. 9 (1), pp. 20158. Date of Electronic Publication: 2019 Dec 27.
DOI: 10.1038/s41598-019-56618-1
Abstrakt: 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.
Databáze: MEDLINE
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