We characterized genome alterations in 1255 clinically annotated lung tumors of all histological subgroups to identify genetically defined and clinically relevant subtypes. More than 55% of all cases had at least one oncogenic genome alteration potentially amenable to specific therapeutic intervention, including several personalized treatment approaches that are already in clinical evaluation. Marked differences in the pattern of genomic alterations existed between and within histological subtypes, thus challenging the original histomorphological diagnosis. Immunohistochemical studies confirmed many of these reassigned subtypes. The reassignment eliminated almost all cases of large cell carcinomas, some of which had therapeutically relevant alterations. Prospective testing of our genomics-based diagnostic algorithm in 5145 lung cancer patients enabled a genome-based diagnosis in 3863 (75%) patients, confirmed the feasibility of rational reassignments of large cell lung cancer, and led to improvement in overall survival in patients with EGFR-mutant or ALK-rearranged cancers. Thus, our findings provide support for broad implementation of genome-based diagnosis of lung cancer.

a genomic-based classification of lung tumors / Clinical Lung Cancer Genome Project (CLCGP); Network Genomic Medicine (NGM);Biospecimens and data source sites: Alex Soltermann; Holger Moch; Odd Terje Brustugun; Steinar Solberg; Marius Lund-Iversen; Åslaug Helland; Thomas Muley; Hans Hoffmann; Philipp A. Schnabel; Yuan Chen; Harry Groen; Wim Timens; Hannie Sietsma; Joachim H. Clement; Walter Weder; Jörg Sänger; Erich Stoelben; Corinna Ludwig; Walburga Engel-Riedel; Egbert Smit; Daniëlle A. M. Heideman; Peter J. F. Snijders; Lucia Nogova; Martin L. Sos; Christian Mattonet; Karin Töpelt; Matthias Scheffler; Eray Goekkurt; Rainer Kappes; Stefan Krüger; Kato Kambartel; Dirk Behringer; Wolfgang Schulte; Wolfgang Galetke; Winfried Randerath; Matthias Heldwein; Andreas Schlesinger; Monika Serke; Khosro Hekmat; Konrad F. Frank; Roland Schnell; Marcel Reiser; Ali-Nuri Hünerlitürkoglu; Stephan Schmitz; Lisa Meffert; Yon-Dschun Ko; Markus Litt-Lampe; Ulrich Gerigk; Rainer Fricke; Benjamin Besse; Christian Brambilla; Sylvie Lantuejoul; Philippe Lorimier; Denis Moro-Sibilot; Federico Cappuzzo; Claudia Ligorio; Stefania Damiani; John K. Field; Russell Hyde; Pierre Validire; Philippe Girard; Lucia A. Muscarella; Vito M. Fazio; Michael Hallek; Jean-Charles Soria; Scott L. Carter; Gad Getz; D. Neil Hayes; Matthew D. Wilkerson; Viktor Achter; Ulrich Lang. - In: SCIENCE TRANSLATIONAL MEDICINE. - ISSN 1946-6234. - ELETTRONICO. - 5:209(2013), pp. 209ra.153.1-209ra.153.28. [10.1126/scitranslmed.3006802]

a genomic-based classification of lung tumors

DAMIANI, STEFANIA;
2013

Abstract

We characterized genome alterations in 1255 clinically annotated lung tumors of all histological subgroups to identify genetically defined and clinically relevant subtypes. More than 55% of all cases had at least one oncogenic genome alteration potentially amenable to specific therapeutic intervention, including several personalized treatment approaches that are already in clinical evaluation. Marked differences in the pattern of genomic alterations existed between and within histological subtypes, thus challenging the original histomorphological diagnosis. Immunohistochemical studies confirmed many of these reassigned subtypes. The reassignment eliminated almost all cases of large cell carcinomas, some of which had therapeutically relevant alterations. Prospective testing of our genomics-based diagnostic algorithm in 5145 lung cancer patients enabled a genome-based diagnosis in 3863 (75%) patients, confirmed the feasibility of rational reassignments of large cell lung cancer, and led to improvement in overall survival in patients with EGFR-mutant or ALK-rearranged cancers. Thus, our findings provide support for broad implementation of genome-based diagnosis of lung cancer.
2013
a genomic-based classification of lung tumors / Clinical Lung Cancer Genome Project (CLCGP); Network Genomic Medicine (NGM);Biospecimens and data source sites: Alex Soltermann; Holger Moch; Odd Terje Brustugun; Steinar Solberg; Marius Lund-Iversen; Åslaug Helland; Thomas Muley; Hans Hoffmann; Philipp A. Schnabel; Yuan Chen; Harry Groen; Wim Timens; Hannie Sietsma; Joachim H. Clement; Walter Weder; Jörg Sänger; Erich Stoelben; Corinna Ludwig; Walburga Engel-Riedel; Egbert Smit; Daniëlle A. M. Heideman; Peter J. F. Snijders; Lucia Nogova; Martin L. Sos; Christian Mattonet; Karin Töpelt; Matthias Scheffler; Eray Goekkurt; Rainer Kappes; Stefan Krüger; Kato Kambartel; Dirk Behringer; Wolfgang Schulte; Wolfgang Galetke; Winfried Randerath; Matthias Heldwein; Andreas Schlesinger; Monika Serke; Khosro Hekmat; Konrad F. Frank; Roland Schnell; Marcel Reiser; Ali-Nuri Hünerlitürkoglu; Stephan Schmitz; Lisa Meffert; Yon-Dschun Ko; Markus Litt-Lampe; Ulrich Gerigk; Rainer Fricke; Benjamin Besse; Christian Brambilla; Sylvie Lantuejoul; Philippe Lorimier; Denis Moro-Sibilot; Federico Cappuzzo; Claudia Ligorio; Stefania Damiani; John K. Field; Russell Hyde; Pierre Validire; Philippe Girard; Lucia A. Muscarella; Vito M. Fazio; Michael Hallek; Jean-Charles Soria; Scott L. Carter; Gad Getz; D. Neil Hayes; Matthew D. Wilkerson; Viktor Achter; Ulrich Lang. - In: SCIENCE TRANSLATIONAL MEDICINE. - ISSN 1946-6234. - ELETTRONICO. - 5:209(2013), pp. 209ra.153.1-209ra.153.28. [10.1126/scitranslmed.3006802]
Clinical Lung Cancer Genome Project (CLCGP); Network Genomic Medicine (NGM);Biospecimens and data source sites: Alex Soltermann; Holger Moch; Odd Terje Brustugun; Steinar Solberg; Marius Lund-Iversen; Åslaug Helland; Thomas Muley; Hans Hoffmann; Philipp A. Schnabel; Yuan Chen; Harry Groen; Wim Timens; Hannie Sietsma; Joachim H. Clement; Walter Weder; Jörg Sänger; Erich Stoelben; Corinna Ludwig; Walburga Engel-Riedel; Egbert Smit; Daniëlle A. M. Heideman; Peter J. F. Snijders; Lucia Nogova; Martin L. Sos; Christian Mattonet; Karin Töpelt; Matthias Scheffler; Eray Goekkurt; Rainer Kappes; Stefan Krüger; Kato Kambartel; Dirk Behringer; Wolfgang Schulte; Wolfgang Galetke; Winfried Randerath; Matthias Heldwein; Andreas Schlesinger; Monika Serke; Khosro Hekmat; Konrad F. Frank; Roland Schnell; Marcel Reiser; Ali-Nuri Hünerlitürkoglu; Stephan Schmitz; Lisa Meffert; Yon-Dschun Ko; Markus Litt-Lampe; Ulrich Gerigk; Rainer Fricke; Benjamin Besse; Christian Brambilla; Sylvie Lantuejoul; Philippe Lorimier; Denis Moro-Sibilot; Federico Cappuzzo; Claudia Ligorio; Stefania Damiani; John K. Field; Russell Hyde; Pierre Validire; Philippe Girard; Lucia A. Muscarella; Vito M. Fazio; Michael Hallek; Jean-Charles Soria; Scott L. Carter; Gad Getz; D. Neil Hayes; Matthew D. Wilkerson; Viktor Achter; Ulrich Lang
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11585/396000
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