Evolutionary trajectories of small cell lung cancer under therapy.

Autor: George J; Department of Translational Genomics, Faculty of Medicine and University Hospital Cologne, University of Cologne, Cologne, Germany. jgeorge@uni-koeln.de.; Department of Otorhinolaryngology, Head and Neck Surgery, Faculty of Medicine and University Hospital Cologne, University Hospital of Cologne, Cologne, Germany. jgeorge@uni-koeln.de., Maas L; Department of Translational Genomics, Faculty of Medicine and University Hospital Cologne, University of Cologne, Cologne, Germany., Abedpour N; Department of Translational Genomics, Faculty of Medicine and University Hospital Cologne, University of Cologne, Cologne, Germany.; Department I of Internal Medicine, Centre for Integrated Oncology Aachen Bonn Cologne Duesseldorf, University Hospital Cologne, Cologne, Germany.; Cancer Research Centre Cologne Essen, Faculty of Medicine and University Hospital Cologne, University of Cologne, Cologne, Germany., Cartolano M; Department of Translational Genomics, Faculty of Medicine and University Hospital Cologne, University of Cologne, Cologne, Germany.; Centre for Molecular Medicine, University of Cologne, Cologne, Germany., Kaiser L; Department of Translational Genomics, Faculty of Medicine and University Hospital Cologne, University of Cologne, Cologne, Germany., Fischer RN; Department I of Internal Medicine, Lung Cancer Group Cologne, University Hospital Cologne, Cologne, Germany., Scheel AH; Institute of Pathology, Medical Faculty, University Hospital Cologne, University of Cologne, Cologne, Germany., Weber JP; Department I of Internal Medicine, Lung Cancer Group Cologne, University Hospital Cologne, Cologne, Germany., Hellmich M; Institute of Medical Statistics, and Computational Biology, Faculty of Medicine and University Hospital Cologne, University of Cologne, Cologne, Germany., Bosco G; Department of Translational Genomics, Faculty of Medicine and University Hospital Cologne, University of Cologne, Cologne, Germany., Volz C; Department I of Internal Medicine, Centre for Integrated Oncology Aachen Bonn Cologne Duesseldorf, University Hospital Cologne, Cologne, Germany.; Centre for Molecular Medicine, University of Cologne, Cologne, Germany., Mueller C; Department of Translational Genomics, Faculty of Medicine and University Hospital Cologne, University of Cologne, Cologne, Germany.; Department of Otorhinolaryngology, Head and Neck Surgery, Faculty of Medicine and University Hospital Cologne, University Hospital of Cologne, Cologne, Germany., Dahmen I; Department of Translational Genomics, Faculty of Medicine and University Hospital Cologne, University of Cologne, Cologne, Germany., John F; Department I of Internal Medicine, Lung Cancer Group Cologne, University Hospital Cologne, Cologne, Germany., Alves CP; Department of Translational Genomics, Faculty of Medicine and University Hospital Cologne, University of Cologne, Cologne, Germany., Werr L; Department of Translational Genomics, Faculty of Medicine and University Hospital Cologne, University of Cologne, Cologne, Germany., Panse JP; Department of Haematology, Oncology, Haemostaseology and Stem Cell Transplantation, University Hospital RWTH Aachen, Aachen, Germany.; Centre for Integrated Oncology, Aachen Bonn Cologne Düsseldorf, Aachen, Germany., Kirschner M; Department of Haematology, Oncology, Haemostaseology and Stem Cell Transplantation, University Hospital RWTH Aachen, Aachen, Germany.; Centre for Integrated Oncology, Aachen Bonn Cologne Düsseldorf, Aachen, Germany., Engel-Riedel W; Department of Pneumology, City of Cologne Municipal Hospitals, Lung Hospital Cologne Merheim, Cologne, Germany., Jürgens J; Department of Pneumology, City of Cologne Municipal Hospitals, Lung Hospital Cologne Merheim, Cologne, Germany., Stoelben E; Thoraxclinic Cologne, Thoracic Surgery, St. Hildegardis-Krankenhaus, Cologne, Germany., Brockmann M; Department of Pathology, City of Cologne Municipal Hospitals, Witten/Herdecke University, Cologne, Germany., Grau S; Department of General Neurosurgery, Centre of Neurosurgery, University Hospital Cologne, Cologne, Germany.; University Medicine Marburg - Campus Fulda, Department of Neurosurgery, Fulda, Germany., Sebastian M; Department of Medicine II, Haematology/Oncology, University Hospital Frankfurt, Goethe University, Frankfurt, Germany.; Frankfurt Cancer Institute, Goethe University Frankfurt, Frankfurt, Germany.; DKFZ, German Cancer Research Centre, German Cancer Consortium, Heidelberg, Germany., Stratmann JA; Department of Medicine II, Haematology/Oncology, University Hospital Frankfurt, Goethe University, Frankfurt, Germany.; Frankfurt Cancer Institute, Goethe University Frankfurt, Frankfurt, Germany., Kern J; Klinikum Würzburg Mitte - Missioklinik site, Pneumology and Respiratory Medicine, Würzburg, Germany., Hummel HD; Translational Oncology/Early Clinical Trial Unit, Comprehensive Cancer Centre Mainfranken, University Hospital Wuerzburg, Wuerzburg, Germany., Hegedüs B; Department of Thoracic Surgery, University Medicine Essen - Ruhrlandklinik, University Duisburg-Essen, Essen, Germany., Schuler M; DKFZ, German Cancer Research Centre, German Cancer Consortium, Heidelberg, Germany.; Department of Medical Oncology, West German Cancer Centre Essen, University Duisburg-Essen, Essen, Germany., Plönes T; Department of Medical Oncology, West German Cancer Centre Essen, University Duisburg-Essen, Essen, Germany.; Division of Thoracic Surgery, Department of General, Thoracic and Vascular Surgery, University Hospital Carl Gustav Carus, Dresden, Germany., Aigner C; Department of Thoracic Surgery, University Medicine Essen - Ruhrlandklinik, University Duisburg-Essen, Essen, Germany.; Department of Thoracic Surgery, Medical University of Vienna, Vienna General Hospital, Vienna, Austria., Elter T; Department I of Internal Medicine, Centre for Integrated Oncology Aachen Bonn Cologne Duesseldorf, University Hospital Cologne, Cologne, Germany., Toepelt K; Department I of Internal Medicine, Centre for Integrated Oncology Aachen Bonn Cologne Duesseldorf, University Hospital Cologne, Cologne, Germany., Ko YD; Comprehensive Cancer Centre CIO Bonn, Bonn, Germany., Kurz S; Department of Respiratory Diseases, Evangelische Lungenklinik, Berlin, Germany., Grohé C; Department of Respiratory Diseases, Evangelische Lungenklinik, Berlin, Germany., Serke M; DGD Lungenklinik Hemer, Internal Medicine, Pneumology and Oncology, Hemer, Germany., Höpker K; Clinic III for Internal Medicine, Faculty of Medicine and University Hospital Cologne, University of Cologne, Cologne, Germany., Hagmeyer L; Clinic of Pneumology and Allergology, Centre for Sleep Medicine and Respiratory Care, Bethanien Hospital Solingen, Solingen, Germany., Doerr F; Department of Thoracic Surgery, University Medicine Essen - Ruhrlandklinik, University Duisburg-Essen, Essen, Germany.; Department of Cardiothoracic Surgery, University Hospital of Cologne, Cologne, Germany., Hekmath K; Department of Cardiothoracic Surgery, University Hospital of Cologne, Cologne, Germany., Strapatsas J; Department of Haematology, Oncology and Clinical Immunology, University Hospital of Duesseldorf, Düsseldorf, Germany., Kambartel KO; Krankenhaus Bethanien Moers, Moers, Germany., Chakupurakal G; Praxis für Hämatologie und Onkologie, Koblenz, Germany., Busch A; Medical Clinic III for Oncology, Haematology, Immune-Oncology and Rheumatology, Centre for Integrative Medicine, University Hospital Bonn, Bonn, Germany., Bauernfeind FG; Medical Clinic III for Oncology, Haematology, Immune-Oncology and Rheumatology, Centre for Integrative Medicine, University Hospital Bonn, Bonn, Germany., Griesinger F; Pius-Hospital Oldenburg, Department of Haematology and Oncology, University Department Internal Medicine-Oncology, University Medicine Oldenburg, Oldenburg, Germany., Luers A; Pius-Hospital Oldenburg, Department of Haematology and Oncology, University Department Internal Medicine-Oncology, University Medicine Oldenburg, Oldenburg, Germany., Dirks W; Pius-Hospital Oldenburg, Department of Haematology and Oncology, University Department Internal Medicine-Oncology, University Medicine Oldenburg, Oldenburg, Germany., Wiewrodt R; Pulmonary Division, Department of Medicine A, Münster University Hospital, Münster, Germany., Luecke A; Pulmonary Division, Department of Medicine A, Münster University Hospital, Münster, Germany., Rodermann E; Onkologie Rheinsieg, Praxisnetzwerk Hämatologie und Internistische Onkologie, Troisdorf, Germany., Diel A; Onkologie Rheinsieg, Praxisnetzwerk Hämatologie und Internistische Onkologie, Troisdorf, Germany., Hagen V; Clinic II for Internal Medicine, St.-Johannes-Hospital Dortmund, Dortmund, Germany., Severin K; Haematologie und Onkologie Köln MV-Zentrum, Cologne, Germany., Ullrich RT; Department I of Internal Medicine, Centre for Integrated Oncology Aachen Bonn Cologne Duesseldorf, University Hospital Cologne, Cologne, Germany.; Centre for Molecular Medicine, University of Cologne, Cologne, Germany., Reinhardt HC; Department of Haematology and Stem Cell Transplantation, University Hospital Essen, Essen, Germany.; West German Cancer Centre, University Hospital Essen, Essen, Germany., Quaas A; Institute of Pathology, Medical Faculty, University Hospital Cologne, University of Cologne, Cologne, Germany., Bogus M; Institute of Legal Medicine, University of Cologne, Cologne, Germany., Courts C; Institute of Legal Medicine, University of Cologne, Cologne, Germany., Nürnberg P; Cologne Centre for Genomics, West German Genome Centre, University of Cologne, Cologne, Germany., Becker K; Cologne Centre for Genomics, West German Genome Centre, University of Cologne, Cologne, Germany., Achter V; Computing Centre, University of Cologne, Cologne, Germany., Büttner R; Institute of Pathology, Medical Faculty, University Hospital Cologne, University of Cologne, Cologne, Germany., Wolf J; Department I of Internal Medicine, Lung Cancer Group Cologne, University Hospital Cologne, Cologne, Germany., Peifer M; Department of Translational Genomics, Faculty of Medicine and University Hospital Cologne, University of Cologne, Cologne, Germany. mpeifer@uni-koeln.de.; Centre for Molecular Medicine, University of Cologne, Cologne, Germany. mpeifer@uni-koeln.de., Thomas RK; Department of Translational Genomics, Faculty of Medicine and University Hospital Cologne, University of Cologne, Cologne, Germany. roman.thomas@uni-koeln.de.; Institute of Pathology, Medical Faculty, University Hospital Cologne, University of Cologne, Cologne, Germany. roman.thomas@uni-koeln.de.; DKFZ, German Cancer Research Centre, German Cancer Consortium, Heidelberg, Germany. roman.thomas@uni-koeln.de.
Jazyk: angličtina
Zdroj: Nature [Nature] 2024 Mar; Vol. 627 (8005), pp. 880-889. Date of Electronic Publication: 2024 Mar 13.
DOI: 10.1038/s41586-024-07177-7
Abstrakt: The evolutionary processes that underlie the marked sensitivity of small cell lung cancer (SCLC) to chemotherapy and rapid relapse are unknown 1-3 . Here we determined tumour phylogenies at diagnosis and throughout chemotherapy and immunotherapy by multiregion sequencing of 160 tumours from 65 patients. Treatment-naive SCLC exhibited clonal homogeneity at distinct tumour sites, whereas first-line platinum-based chemotherapy led to a burst in genomic intratumour heterogeneity and spatial clonal diversity. We observed branched evolution and a shift to ancestral clones underlying tumour relapse. Effective radio- or immunotherapy induced a re-expansion of founder clones with acquired genomic damage from first-line chemotherapy. Whereas TP53 and RB1 alterations were exclusively part of the common ancestor, MYC family amplifications were frequently not constituents of the founder clone. At relapse, emerging subclonal mutations affected key genes associated with SCLC biology, and tumours harbouring clonal CREBBP/EP300 alterations underwent genome duplications. Gene-damaging TP53 alterations and co-alterations of TP53 missense mutations with TP73, CREBBP/EP300 or FMN2 were significantly associated with shorter disease relapse following chemotherapy. In summary, we uncover key processes of the genomic evolution of SCLC under therapy, identify the common ancestor as the source of clonal diversity at relapse and show central genomic patterns associated with sensitivity and resistance to chemotherapy.
(© 2024. The Author(s).)
Databáze: MEDLINE
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