Evolutionary trajectories of small cell lung cancer under therapy

Julie George (), Lukas Maas, Nima Abedpour, Maria Cartolano, Laura Kaiser, Rieke N. Fischer, Andreas H. Scheel, Jan-Philipp Weber, Martin Hellmich, Graziella Bosco, Caroline Volz, Christian Mueller, Ilona Dahmen, Felix John, Cleidson Padua Alves, Lisa Werr, Jens Peter Panse, Martin Kirschner, Walburga Engel-Riedel, Jessica Jürgens, Erich Stoelben, Michael Brockmann, Stefan Grau, Martin Sebastian, Jan A. Stratmann, Jens Kern, Horst-Dieter Hummel, Balazs Hegedüs, Martin Schuler, Till Plönes, Clemens Aigner, Thomas Elter, Karin Toepelt, Yon-Dschun Ko, Sylke Kurz, Christian Grohé, Monika Serke, Katja Höpker, Lars Hagmeyer, Fabian Doerr, Khosro Hekmath, Judith Strapatsas, Karl-Otto Kambartel, Geothy Chakupurakal, Annette Busch, Franz-Georg Bauernfeind, Frank Griesinger, Anne Luers, Wiebke Dirks, Rainer Wiewrodt, Andrea Luecke, Ernst Rodermann, Andreas Diel, Volker Hagen, Kai Severin, Roland T. Ullrich, Hans Christian Reinhardt, Alexander Quaas, Magdalena Bogus, Cornelius Courts, Peter Nürnberg, Kerstin Becker, Viktor Achter, Reinhard Büttner, Jürgen Wolf, Martin Peifer () and Roman K. Thomas ()
Additional contact information
Julie George: University of Cologne
Lukas Maas: University of Cologne
Nima Abedpour: University of Cologne
Maria Cartolano: University of Cologne
Laura Kaiser: University of Cologne
Rieke N. Fischer: University Hospital Cologne
Andreas H. Scheel: University of Cologne
Jan-Philipp Weber: University Hospital Cologne
Martin Hellmich: University of Cologne
Graziella Bosco: University of Cologne
Caroline Volz: University Hospital Cologne
Christian Mueller: University of Cologne
Ilona Dahmen: University of Cologne
Felix John: University Hospital Cologne
Cleidson Padua Alves: University of Cologne
Lisa Werr: University of Cologne
Jens Peter Panse: University Hospital RWTH Aachen
Martin Kirschner: University Hospital RWTH Aachen
Walburga Engel-Riedel: City of Cologne Municipal Hospitals, Lung Hospital Cologne Merheim
Jessica Jürgens: City of Cologne Municipal Hospitals, Lung Hospital Cologne Merheim
Erich Stoelben: Thoraxclinic Cologne, Thoracic Surgery, St. Hildegardis-Krankenhaus
Michael Brockmann: Witten/Herdecke University
Stefan Grau: University Hospital Cologne
Martin Sebastian: Goethe University
Jan A. Stratmann: Goethe University
Jens Kern: Klinikum Würzburg Mitte – Missioklinik site, Pneumology and Respiratory Medicine
Horst-Dieter Hummel: University Hospital Wuerzburg
Balazs Hegedüs: University Duisburg-Essen
Martin Schuler: DKFZ, German Cancer Research Centre, German Cancer Consortium
Till Plönes: University Duisburg-Essen
Clemens Aigner: University Duisburg-Essen
Thomas Elter: University Hospital Cologne
Karin Toepelt: University Hospital Cologne
Yon-Dschun Ko: Comprehensive Cancer Centre CIO Bonn
Sylke Kurz: Evangelische Lungenklinik
Christian Grohé: Evangelische Lungenklinik
Monika Serke: DGD Lungenklinik Hemer, Internal Medicine, Pneumology and Oncology
Katja Höpker: University of Cologne
Lars Hagmeyer: Clinic of Pneumology and Allergology, Centre for Sleep Medicine and Respiratory Care, Bethanien Hospital Solingen
Fabian Doerr: University Duisburg-Essen
Khosro Hekmath: University Hospital of Cologne
Judith Strapatsas: University Hospital of Duesseldorf
Karl-Otto Kambartel: Krankenhaus Bethanien Moers
Geothy Chakupurakal: Praxis für Hämatologie und Onkologie
Annette Busch: University Hospital Bonn
Franz-Georg Bauernfeind: University Hospital Bonn
Frank Griesinger: University Medicine Oldenburg
Anne Luers: University Medicine Oldenburg
Wiebke Dirks: University Medicine Oldenburg
Rainer Wiewrodt: Pulmonary Division, Department of Medicine A, Münster University Hospital
Andrea Luecke: Pulmonary Division, Department of Medicine A, Münster University Hospital
Ernst Rodermann: Onkologie Rheinsieg, Praxisnetzwerk Hämatologie und Internistische Onkologie
Andreas Diel: Onkologie Rheinsieg, Praxisnetzwerk Hämatologie und Internistische Onkologie
Volker Hagen: Clinic II for Internal Medicine, St.-Johannes-Hospital Dortmund
Kai Severin: Haematologie und Onkologie Köln MV-Zentrum
Roland T. Ullrich: University Hospital Cologne
Hans Christian Reinhardt: University Hospital Essen
Alexander Quaas: University of Cologne
Magdalena Bogus: University of Cologne
Cornelius Courts: University of Cologne
Peter Nürnberg: University of Cologne
Kerstin Becker: University of Cologne
Viktor Achter: University of Cologne
Reinhard Büttner: University of Cologne
Jürgen Wolf: University Hospital Cologne
Martin Peifer: University of Cologne
Roman K. Thomas: University of Cologne

Nature, 2024, vol. 627, issue 8005, 880-889

Abstract: Abstract The evolutionary processes that underlie the marked sensitivity of small cell lung cancer (SCLC) to chemotherapy and rapid relapse are unknown1–3. 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.

Date: 2024
References: Add references at CitEc
Citations: View citations in EconPapers (1)

Downloads: (external link)
https://www.nature.com/articles/s41586-024-07177-7 Abstract (text/html)
Access to the full text of the articles in this series is restricted.

Related works:
This item may be available elsewhere in EconPapers: Search for items with the same title.

Export reference: BibTeX RIS (EndNote, ProCite, RefMan) HTML/Text

Persistent link: https://EconPapers.repec.org/RePEc:nat:nature:v:627:y:2024:i:8005:d:10.1038_s41586-024-07177-7

Ordering information: This journal article can be ordered from
https://www.nature.com/

DOI: 10.1038/s41586-024-07177-7

Access Statistics for this article

Nature is currently edited by Magdalena Skipper

More articles in Nature from Nature
Bibliographic data for series maintained by Sonal Shukla () and Springer Nature Abstracting and Indexing ().