{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,21]],"date-time":"2026-09-21T15:02:02Z","timestamp":1790002922083,"version":"4.0.1"},"reference-count":42,"publisher":"American Association for Cancer Research (AACR)","issue":"2","content-domain":{"domain":["aacrjournals.org"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2014,2,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>The 8p12 locus (containing the FGFR1 tyrosine kinase gene) is frequently amplified in squamous cell lung cancer. However, it is currently unknown which of the 8p12-amplified tumors are also sensitive to fibroblast growth factor receptor (FGFR) inhibition. We found that, in contrast with other recurrent amplifications, the 8p12 region included multiple centers of amplification, suggesting marked genomic heterogeneity. FGFR1-amplified tumor cells were dependent on FGFR ligands in vitro and in vivo. Furthermore, ectopic expression of FGFR1 was oncogenic, which was enhanced by expression of MYC. We found that MYC was coexpressed in 40% of FGFR1-amplified tumors. Tumor cells coexpressing MYC were more sensitive to FGFR inhibition, suggesting that patients with FGFR1-amplified and MYC-overexpressing tumors may benefit from FGFR inhibitor therapy. Thus, both cell-autonomous and non\u2013cell-autonomous mechanisms of transformation modulate FGFR dependency in FGFR1-amplified lung cancer, which may have implications for patient selection for treatment with FGFR inhibitors.<\/jats:p>\n                  <jats:p>Significance: Amplification of FGFR1 is one of the most frequent candidate targets in lung cancer. Here, we show that multiple factors affect the tumorigenic potential of FGFR1, thus providing clinical hypotheses for refinement of patient selection. Cancer Discov; 4(2); 246\u201357. \u00a92013 AACR.<\/jats:p>\n                  <jats:p>See related commentary by Lockwood and Politi, p. 152<\/jats:p>\n                  <jats:p>This article is highlighted in the In This Issue feature, p. 131<\/jats:p>","DOI":"10.1158\/2159-8290.cd-13-0323","type":"journal-article","created":{"date-parts":[[2013,12,3]],"date-time":"2013-12-03T23:14:23Z","timestamp":1386112463000},"page":"246-257","update-policy":"https:\/\/doi.org\/10.1158\/crossmark_policy","source":"Crossref","is-referenced-by-count":87,"title":["Cell-Autonomous and Non\u2013Cell-Autonomous Mechanisms of Transformation by Amplified\n                    <i>FGFR1<\/i>\n                    in Lung Cancer"],"prefix":"10.1158","volume":"4","author":[{"given":"Florian","family":"Malchers","sequence":"first","affiliation":[{"name":"Authors' Affiliations: 1Department of Translational Genomics, University of Cologne; 2Max-Planck-Institute for Neurological Research; Institutes of 3Pathology and 4Virology, University of Cologne;5Department I of Internal Medicine and Center for Integrated Oncology, University Hospital of Cologne; 6Blackfield AG, Cologne; 7Technical University Dortmund, Dortmund, Germany; 8Medical Oncology and 9Institute of Pathology, Cantonal Hospital, Luzern; 10Novartis Pharma AG, Basel, Switzerland; and 11Division of Natural Products Chemistry, CSIR\u2013Indian Institute of Chemical Technology, Tarnaka, Hyderabad, India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Felix","family":"Dietlein","sequence":"additional","affiliation":[{"name":"Authors' Affiliations: 1Department of Translational Genomics, University of Cologne; 2Max-Planck-Institute for Neurological Research; Institutes of 3Pathology and 4Virology, University of Cologne;5Department I of Internal Medicine and Center for Integrated Oncology, University Hospital of Cologne; 6Blackfield AG, Cologne; 7Technical University Dortmund, Dortmund, Germany; 8Medical Oncology and 9Institute of Pathology, Cantonal Hospital, Luzern; 10Novartis Pharma AG, Basel, Switzerland; and 11Division of Natural Products Chemistry, CSIR\u2013Indian Institute of Chemical Technology, Tarnaka, Hyderabad, India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jakob","family":"Sch\u00f6ttle","sequence":"additional","affiliation":[{"name":"Authors' Affiliations: 1Department of Translational Genomics, University of Cologne; 2Max-Planck-Institute for Neurological Research; Institutes of 3Pathology and 4Virology, University of Cologne;5Department I of Internal Medicine and Center for Integrated Oncology, University Hospital of Cologne; 6Blackfield AG, Cologne; 7Technical University Dortmund, Dortmund, Germany; 8Medical Oncology and 9Institute of Pathology, Cantonal Hospital, Luzern; 10Novartis Pharma AG, Basel, Switzerland; and 11Division of Natural Products Chemistry, CSIR\u2013Indian Institute of Chemical Technology, Tarnaka, Hyderabad, India"},{"name":"Authors' Affiliations: 1Department of Translational Genomics, University of Cologne; 2Max-Planck-Institute for Neurological Research; Institutes of 3Pathology and 4Virology, University of Cologne;5Department I of Internal Medicine and Center for Integrated Oncology, University Hospital of Cologne; 6Blackfield AG, Cologne; 7Technical University Dortmund, Dortmund, Germany; 8Medical Oncology and 9Institute of Pathology, Cantonal Hospital, Luzern; 10Novartis Pharma AG, Basel, Switzerland; 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2Max-Planck-Institute for Neurological Research; Institutes of 3Pathology and 4Virology, University of Cologne;5Department I of Internal Medicine and Center for Integrated Oncology, University Hospital of Cologne; 6Blackfield AG, Cologne; 7Technical University Dortmund, Dortmund, Germany; 8Medical Oncology and 9Institute of Pathology, Cantonal Hospital, Luzern; 10Novartis Pharma AG, Basel, Switzerland; and 11Division of Natural Products Chemistry, CSIR\u2013Indian Institute of Chemical Technology, Tarnaka, Hyderabad, India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kerstin","family":"Albus","sequence":"additional","affiliation":[{"name":"Authors' Affiliations: 1Department of Translational Genomics, University of Cologne; 2Max-Planck-Institute for Neurological Research; Institutes of 3Pathology and 4Virology, University of Cologne;5Department I of Internal Medicine and Center for Integrated Oncology, University Hospital of Cologne; 6Blackfield AG, Cologne; 7Technical University Dortmund, Dortmund, Germany; 8Medical Oncology and 9Institute of Pathology, Cantonal Hospital, Luzern; 10Novartis Pharma AG, Basel, Switzerland; and 11Division of Natural Products Chemistry, CSIR\u2013Indian Institute of Chemical Technology, Tarnaka, Hyderabad, India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lynnette","family":"Fernandez-Cuesta","sequence":"additional","affiliation":[{"name":"Authors' Affiliations: 1Department of Translational Genomics, University of Cologne; 2Max-Planck-Institute for Neurological Research; Institutes of 3Pathology and 4Virology, University of Cologne;5Department I of Internal Medicine and Center for Integrated Oncology, University Hospital of Cologne; 6Blackfield AG, Cologne; 7Technical University Dortmund, Dortmund, Germany; 8Medical Oncology and 9Institute of Pathology, Cantonal Hospital, Luzern; 10Novartis Pharma AG, Basel, Switzerland; and 11Division of Natural Products Chemistry, CSIR\u2013Indian Institute of Chemical Technology, Tarnaka, Hyderabad, India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Johannes M.","family":"Heuckmann","sequence":"additional","affiliation":[{"name":"Authors' Affiliations: 1Department of Translational Genomics, University of Cologne; 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