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1. Evolutionary trajectories of small cell lung cancer under therapy

Author

George, Julie, Maas, Lukas, Abedpour, Nima, Cartolano, Maria, Kaiser, Laura, Fischer, Rieke N., Scheel, Andreas H., Weber, Jan-Philipp, Hellmich, Martin, Bosco, Graziella, Volz, Caroline, Mueller, Christian, Dahmen, Ilona, John, Felix, Alves, Cleidson Padua, Werr, Lisa, Panse, Jens Peter, Kirschner, Martin, Engel-Riedel, Walburga, Jürgens, Jessica, Stoelben, Erich, Brockmann, Michael, Grau, Stefan, Sebastian, Martin, Stratmann, Jan A., Kern, Jens, Hummel, Horst-Dieter, Hegedüs, Balazs, Schuler, Martin, Plönes, Till, Aigner, Clemens, Elter, Thomas, Toepelt, Karin, Ko, Yon-Dschun, Kurz, Sylke, Grohé, Christian, Serke, Monika, Höpker, Katja, Hagmeyer, Lars, Doerr, Fabian, Hekmath, Khosro, Strapatsas, Judith, Kambartel, Karl-Otto, Chakupurakal, Geothy, Busch, Annette, Bauernfeind, Franz-Georg, Griesinger, Frank, Luers, Anne, Dirks, Wiebke, Wiewrodt, Rainer, Luecke, Andrea, Rodermann, Ernst, Diel, Andreas, Hagen, Volker, Severin, Kai, Ullrich, Roland T., Reinhardt, Hans Christian, Quaas, Alexander, Bogus, Magdalena, Courts, Cornelius, Nürnberg, Peter, Becker, Kerstin, Achter, Viktor, Büttner, Reinhard, Wolf, Jürgen, Peifer, Martin, and Thomas, Roman K.

Published
2024
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2. Ramucirumab plus erlotinib in patients with untreated, EGFR-mutated, advanced non-small-cell lung cancer (RELAY): a randomised, double-blind, placebo-controlled, phase 3 trial

Author

Chu, Quincy, Cortot, Alexis, Pujol, Jean-Louis, Moro-Sibilot, Denis, Fabre, Elizabeth, Lamour, Corinne, Bischoff, Helge, Kollmeier, Jens, Reck, Martin, Kimmich, Martin, Engel-Riedel, Walburga, Hammerschmidt, Stefan, Schütte, Wolfgang, Syrigos, Konstantinos, Ho, James Chung Man, Au, Kwok-Hung, Novello, Silvia, Ardizzoni, Andrea, Pasello, Giulia, Gregorc, Vanessa, Del Conte, Alessandro, Galetta, Domenico, Takahashi, Toshiaki, Nakagawa, Kazuhiko, Nishio, Makoto, Yoh, Kiyotaka, Seto, Takashi, Imamura, Fumio, Kumagai, Toru, Hotta, Katsuyuki, Goto, Yasushi, Hosomi, Yukio, Sakai, Hiroshi, Takiguchi, Yuichi, Kim, Young Hak, Kurata, Takayasu, Yamaguchi, Hiroyuki, Daga, Haruko, Okamoto, Isamu, Satouchi, Miyako, Ikeda, Satoshi, Kasahara, Kazuo, Atagi, Shinji, Azuma, Koichi, Aoe, Keisuke, Horio, Yoshitsugu, Yamamoto, Nobuyuki, Tanaka, Hiroshi, Watanabe, Satoshi, Nogami, Naoyuki, Ozaki, Tomohiro, Koyama, Ryo, Hirashima, Tomonori, Kaneda, Hiroyasu, Tomii, Keisuke, Fujita, Yuka, Seike, Masahiro, Nishimura, Naoki, Kato, Terufumi, Ichiki, Masao, Saka, Hideo, Hirano, Katsuya, Nakahara, Yasuharu, Sugawara, Shunichi, Park, Keunchil, Kim, Sang-We, Min, Young Joo, Lee, Hyun Woo, Kang, Jin-Hyoung, An, Ho Jung, Lee, Ki Hyeong, Kim, Jin-Soo, Lee, Gyeong-Won, Lee, Sung Yong, Alexandru, Aurelia, Udrea, Anghel Adrian, Juan-Vidal, Óscar, Nadal-Alforja, Ernest, Gil-Bazo, Ignacio, Ponce-Aix, Santiago, Paz-Ares, Luis, Rubio-Viqueira, Belén, Alonso Garcia, Miriam, Felip Font, Enriqueta, Fuentes Pradera, Jose, Coves Sarto, Juan, Lin, Meng-Chih, Su, Wu-Chou, Hsia, Te-Chun, Chang, Gee-Chen, Wei, Yu-Feng, Chiu, Chao-Hua, Shih, Jin-Yuan, Su, Jian, Cicin, Irfan, Goksel, Tuncay, Harputluoglu, Hakan, Ozyilkan, Ozgur, Henning, Ivo, Popat, Sanjay, Hatcher, Olivia, Mileham, Kathryn, Acoba, Jared, Garon, Edward, Jung, Gabriel, Raj, Moses, Martin, William, Dakhil, Shaker, Garon, Edward B, Ponce Aix, Santiago, Nadal, Ernest, Au, Kwok Hung, Enatsu, Sotaro, Zimmermann, Annamaria, Frimodt-Moller, Bente, and Visseren-Grul, Carla

Published
2019
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3. Supplementary Data from Blood-Based Gene Expression Signatures in Non–Small Cell Lung Cancer

Author

Zander, Thomas, primary, Hofmann, Andrea, primary, Staratschek-Jox, Andrea, primary, Classen, Sabine, primary, Debey-Pascher, Svenja, primary, Maisel, Daniela, primary, Ansén, Sascha, primary, Hahn, Moritz, primary, Beyer, Marc, primary, Thomas, Roman K., primary, Gathof, Birgit, primary, Mauch, Cornelia, primary, Delank, Karl-Stefan, primary, Engel-Riedel, Walburga, primary, Wichmann, H.-Erich, primary, Stoelben, Erich, primary, Schultze, Joachim L., primary, and Wolf, Jürgen, primary

Published
2023
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4. Three-Year Follow-Up of a Randomized Phase II Trial on Refinement of Early-Stage NSCLC Adjuvant Chemotherapy with Cisplatin and Pemetrexed versus Cisplatin and Vinorelbine (the TREAT Study)

Author

Kreuter, Michael, Vansteenkiste, Johan, Fischer, Jürgen R., Eberhardt, Wilfried E., Zabeck, Heike, Kollmeier, Jens, Serke, Monika, Frickhofen, Norbert, Reck, Martin, Engel-Riedel, Walburga, Neumann, Silke, Thomeer, Michiel, Schumann, Christian, De Leyn, Paul, Graeter, Thomas, Stamatis, Georgios, Griesinger, Frank, and Thomas, Michael

Published
2016
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5. Overcoming EGFRG724S-mediated osimertinib resistance through unique binding characteristics of second-generation EGFR inhibitors

Author

Fassunke, Jana, Müller, Fabienne, Keul, Marina, Michels, Sebastian, Dammert, Marcel A., Schmitt, Anna, Plenker, Dennis, Lategahn, Jonas, Heydt, Carina, Brägelmann, Johannes, Tumbrink, Hannah L., Alber, Yannic, Klein, Sebastian, Heimsoeth, Alena, Dahmen, Ilona, Fischer, Rieke N., Scheffler, Matthias, Ihle, Michaela A., Priesner, Vanessa, Scheel, Andreas H., Wagener, Svenja, Kron, Anna, Frank, Konrad, Garbert, Katia, Persigehl, Thorsten, Püsken, Michael, Haneder, Stefan, Schaaf, Bernhard, Rodermann, Ernst, Engel-Riedel, Walburga, Felip, Enriqueta, Smit, Egbert F., Merkelbach-Bruse, Sabine, Reinhardt, H. Christian, Kast, Stefan M., Wolf, Jürgen, Rauh, Daniel, Büttner, Reinhard, and Sos, Martin L.

Published
2018
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7. GILT—A randomised phase III study of oral vinorelbine and cisplatin with concomitant radiotherapy followed by either consolidation therapy with oral vinorelbine and cisplatin or best supportive care alone in stage III non-small cell lung cancer

Author

Flentje, Michael, Huber, Rudolf M., Engel-Riedel, Walburga, Andreas, Stefan, Kollmeier, Jens, Staar, Susanne, Dickgreber, Nicolas, Vaissiere, Nathalie, De Almeida, Cecilia, Edlich, Birgit, and Fietkau, Rainer

Published
2016
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8. Definition of a fluorescence in-situ hybridization score identifies high- and low-level FGFR1 amplification types in squamous cell lung cancer

Author

Schildhaus, Hans-Ulrich, Heukamp, Lukas C, Merkelbach-Bruse, Sabine, Riesner, Katharina, Schmitz, Katja, Binot, Elke, Paggen, Ellen, Albus, Kerstin, Schulte, Wolfgang, Ko, Yon-Dschun, Schlesinger, Andreas, Ansén, Sascha, Engel-Riedel, Walburga, Brockmann, Michael, Serke, Monika, Gerigk, Ulrich, Huss, Sebastian, Göke, Friederike, Perner, Sven, Hekmat, Khosro, Frank, Konrad F, Reiser, Marcel, Schnell, Roland, Bos, Marc, Mattonet, Christian, Sos, Martin, Stoelben, Erich, Wolf, Jürgen, Zander, Thomas, and Buettner, Reinhard

Published
2012
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10. Clinicopathological Characteristics of RET Rearranged Lung Cancer in European Patients

Author

Michels, Sebastian, Scheel, Andreas Hans, Scheffler, Matthias, Schultheis, Anne Maria, Gautschi, Oliver, Aebersold, Franziska, Diebold, Joachim, Pall, Georg, Rothschild, Sacha, Bubendorf, Lukas, Hartmann, Wolfgang, Heukamp, Lukas, Schildhaus, Hans-Ulrich, Fassunke, Jana, Ihle, Michaela Angelika, Künstlinger, Helen, Heydt, Carina, Fischer, Rieke, Nogovà, Lucia, Mattonet, Christian, Hein, Rebecca, Adams, Anne, Gerigk, Ulrich, Schulte, Wolfgang, Lüders, Heike, Grohé, Christian, Graeven, Ullrich, Müller-Naendrup, Clemens, Draube, Andreas, Kambartel, Karl-Otto, Krüger, Stefan, Schulze-Olden, Susanne, Serke, Monika, Engel-Riedel, Walburga, Kaminsky, Britta, Randerath, Winfried, Merkelbach-Bruse, Sabine, Büttner, Reinhard, and Wolf, Jürgen

Published
2016
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14. Genomic Profiling Identifies Outcome-Relevant Mechanisms of Innate and Acquired Resistance to Third-Generation Epidermal Growth Factor Receptor Tyrosine Kinase Inhibitor Therapy in Lung Cancer

Author

Michels, Sebastian, primary, Heydt, Carina, additional, van Veggel, Bianca, additional, Deschler-Baier, Barbara, additional, Pardo, Nuria, additional, Monkhorst, Kim, additional, Rüsseler, Vanessa, additional, Stratmann, Jan, additional, Griesinger, Frank, additional, Steinhauser, Susanne, additional, Kostenko, Anna, additional, Diebold, Joachim, additional, Fassunke, Jana, additional, Fischer, Rieke, additional, Engel-Riedel, Walburga, additional, Gautschi, Oliver, additional, Geissinger, Eva, additional, Haneder, Stefan, additional, Ihle, Michaela A., additional, Kopp, Hans-Georg, additional, de Langen, Adrianus J., additional, Martinez-Marti, Alex, additional, Nogova, Lucia, additional, Persigehl, Thorsten, additional, Plenker, Dennis, additional, Puesken, Michael, additional, Rodermann, Ernst, additional, Rosenwald, Andreas, additional, Scheel, Andreas H., additional, Scheffler, Matthias, additional, Spengler, Werner, additional, Seggewiss-Bernhardt, Ruth, additional, Brägelmann, Johannes, additional, Sebastian, Martin, additional, Vrugt, Bart, additional, Hellmich, Martin, additional, Sos, Martin L., additional, Heukamp, Lukas C., additional, Felip, Enriqueta, additional, Merkelbach-Bruse, Sabine, additional, Smit, Egbert F., additional, Büttner, Reinhard, additional, and Wolf, Jürgen, additional

Published
2019
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15. Ramucirumab plus erlotinib in patients with untreated, EGFR-mutated, advanced non-small-cell lung cancer (RELAY): a randomised, double-blind, placebo-controlled, phase 3 trial

Author

Nakagawa, Kazuhiko, primary, Garon, Edward B, additional, Seto, Takashi, additional, Nishio, Makoto, additional, Ponce Aix, Santiago, additional, Paz-Ares, Luis, additional, Chiu, Chao-Hua, additional, Park, Keunchil, additional, Novello, Silvia, additional, Nadal, Ernest, additional, Imamura, Fumio, additional, Yoh, Kiyotaka, additional, Shih, Jin-Yuan, additional, Au, Kwok Hung, additional, Moro-Sibilot, Denis, additional, Enatsu, Sotaro, additional, Zimmermann, Annamaria, additional, Frimodt-Moller, Bente, additional, Visseren-Grul, Carla, additional, Reck, Martin, additional, Chu, Quincy, additional, Cortot, Alexis, additional, Pujol, Jean-Louis, additional, Fabre, Elizabeth, additional, Lamour, Corinne, additional, Bischoff, Helge, additional, Kollmeier, Jens, additional, Kimmich, Martin, additional, Engel-Riedel, Walburga, additional, Hammerschmidt, Stefan, additional, Schütte, Wolfgang, additional, Syrigos, Konstantinos, additional, Ho, James Chung Man, additional, Au, Kwok-Hung, additional, Ardizzoni, Andrea, additional, Pasello, Giulia, additional, Gregorc, Vanessa, additional, Del Conte, Alessandro, additional, Galetta, Domenico, additional, Takahashi, Toshiaki, additional, Nakagawa, Kazuhiko, additional, Kumagai, Toru, additional, Hotta, Katsuyuki, additional, Goto, Yasushi, additional, Hosomi, Yukio, additional, Sakai, Hiroshi, additional, Takiguchi, Yuichi, additional, Kim, Young Hak, additional, Kurata, Takayasu, additional, Yamaguchi, Hiroyuki, additional, Daga, Haruko, additional, Okamoto, Isamu, additional, Satouchi, Miyako, additional, Ikeda, Satoshi, additional, Kasahara, Kazuo, additional, Atagi, Shinji, additional, Azuma, Koichi, additional, Aoe, Keisuke, additional, Horio, Yoshitsugu, additional, Yamamoto, Nobuyuki, additional, Tanaka, Hiroshi, additional, Watanabe, Satoshi, additional, Nogami, Naoyuki, additional, Ozaki, Tomohiro, additional, Koyama, Ryo, additional, Hirashima, Tomonori, additional, Kaneda, Hiroyasu, additional, Tomii, Keisuke, additional, Fujita, Yuka, additional, Seike, Masahiro, additional, Nishimura, Naoki, additional, Kato, Terufumi, additional, Ichiki, Masao, additional, Saka, Hideo, additional, Hirano, Katsuya, additional, Nakahara, Yasuharu, additional, Sugawara, Shunichi, additional, Kim, Sang-We, additional, Min, Young Joo, additional, Lee, Hyun Woo, additional, Kang, Jin-Hyoung, additional, An, Ho Jung, additional, Lee, Ki Hyeong, additional, Kim, Jin-Soo, additional, Lee, Gyeong-Won, additional, Lee, Sung Yong, additional, Alexandru, Aurelia, additional, Udrea, Anghel Adrian, additional, Juan-Vidal, Óscar, additional, Nadal-Alforja, Ernest, additional, Gil-Bazo, Ignacio, additional, Ponce-Aix, Santiago, additional, Rubio-Viqueira, Belén, additional, Alonso Garcia, Miriam, additional, Felip Font, Enriqueta, additional, Fuentes Pradera, Jose, additional, Coves Sarto, Juan, additional, Lin, Meng-Chih, additional, Su, Wu-Chou, additional, Hsia, Te-Chun, additional, Chang, Gee-Chen, additional, Wei, Yu-Feng, additional, Su, Jian, additional, Cicin, Irfan, additional, Goksel, Tuncay, additional, Harputluoglu, Hakan, additional, Ozyilkan, Ozgur, additional, Henning, Ivo, additional, Popat, Sanjay, additional, Hatcher, Olivia, additional, Mileham, Kathryn, additional, Acoba, Jared, additional, Garon, Edward, additional, Jung, Gabriel, additional, Raj, Moses, additional, Martin, William, additional, and Dakhil, Shaker, additional

Published
2019
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16. Genomic Profiling Identifies Outcome-Relevant Mechanisms of Innate and Acquired Resistance to Third-Generation Epidermal Growth Factor Receptor Tyrosine Kinase Inhibitor Therapy in Lung Cancer

Author

Michels, Sebastian, Heydt, Carina, van Veggel, Bianca, Deschler-Baier, Barbara, Pardo, Nuria, Monkhorst, Kim, Ruesseler, Vanessa, Stratmann, Jan, Griesinger, Frank, Steinhauser, Susanne, Kostenko, Anna, Diebold, Joachim, Fassunke, Jana, Fischer, Rieke, Engel-Riedel, Walburga, Gautschi, Oliver, Geissinger, Eva, Haneder, Stefan, Ihle, Michaela A., Kopp, Hans-Georg, de Langen, Adrianus J., Martinez-Marti, Alex, Nogova, Lucia, Persigehl, Thorsten, Plenker, Dennis, Puesken, Michael, Rodermann, Ernst, Rosenwald, Andreas, Scheel, Andreas H., Scheffler, Matthias, Spengler, Werner, Seggewiss-Bernhardt, Ruth, Braegelmann, Johannes, Sebastian, Martin, Vrugt, Bart, Hellmich, Martin, Sos, Martin L., Heukamp, Lukas C., Felip, Enriqueta, Merkelbach-Bruse, Sabine, Smit, Egbert F., Buettner, Reinhard, Wolf, Juergen, Michels, Sebastian, Heydt, Carina, van Veggel, Bianca, Deschler-Baier, Barbara, Pardo, Nuria, Monkhorst, Kim, Ruesseler, Vanessa, Stratmann, Jan, Griesinger, Frank, Steinhauser, Susanne, Kostenko, Anna, Diebold, Joachim, Fassunke, Jana, Fischer, Rieke, Engel-Riedel, Walburga, Gautschi, Oliver, Geissinger, Eva, Haneder, Stefan, Ihle, Michaela A., Kopp, Hans-Georg, de Langen, Adrianus J., Martinez-Marti, Alex, Nogova, Lucia, Persigehl, Thorsten, Plenker, Dennis, Puesken, Michael, Rodermann, Ernst, Rosenwald, Andreas, Scheel, Andreas H., Scheffler, Matthias, Spengler, Werner, Seggewiss-Bernhardt, Ruth, Braegelmann, Johannes, Sebastian, Martin, Vrugt, Bart, Hellmich, Martin, Sos, Martin L., Heukamp, Lukas C., Felip, Enriqueta, Merkelbach-Bruse, Sabine, Smit, Egbert F., Buettner, Reinhard, and Wolf, Juergen

Abstract

PURPOSE Third-generation epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) are effective in acquired resistance (AR) to early-generation EGFR TKIs in EGFR-mutant lung cancer. However, efficacy is marked by interindividual heterogeneity. We present the molecular profiles of pretreatment and post-treatment samples from patients treated with third-generation EGFR TKIs and their impact on treatment outcomes. METHODS Using the databases of two lung cancer networks and two lung cancer centers, we molecularly characterized 124 patients with EGFR p. T790M-positive AR to early-generation EGFR TKIs. In 56 patients, correlative analyses of third-generation EGFR TKI treatment outcomes and molecular characteristics were feasible. In addition, matched post-treatment biopsy samples were collected for 29 patients with progression to third-generation EGFR TKIs. RESULTS Co-occurring genetic aberrations were found in 74.4% of EGFR p. T790-positive samples (n = 124). Mutations in TP53 were the most frequent aberrations detected (44.5%; n = 53) and had no significant impact on third-generation EGFR TKI treatment. Mesenchymal-epithelial transition factor (MET) amplifications were found in 5% of samples (n = 6) and reduced efficacy of third-generation EGFR TKIs significantly (eg, median progression-free survival, 1.0 months; 95% CI, 0.37 to 1.72 v 8.2 months; 95% CI, 1.69 to 14.77 months; P <= .001). Genetic changes in the 29 samples with AR to third-generation EGFR TKIs were found in EGFR (eg, p.T790M loss, acquisition of p.C797S or p.G724S) or in other genes (eg, MET amplification, KRAS mutations). CONCLUSION Additional genetic aberrations are frequent in EGFR-mutant lung cancer and may mediate innate and AR to third-generation EGFR TKIs. MET amplification was strongly associated with primary treatment failure and was a common mechanism of AR to third-generation EGFR TKIs. Thus, combining EGFR inhibitors with TKIs targeting common mechanisms of resistance may del

Published
2019

17. BIOLUMA: A phase II trial of nivolumab in combination with ipilimumab to evaluate efficacy and safety in lung cancer and to evaluate biomarkers predictive for response—Preliminary results from the SCLC cohort.

Author

Fischer, Rieke Nila, primary, George, Julie, additional, Scheel, Andreas H., additional, Schloesser, Hans Anton, additional, Vehreschild, Maria, additional, Brossart, Peter, additional, Engel-Riedel, Walburga, additional, Griesinger, Frank, additional, Grohé, Christian, additional, Kambartel, Karl-Otto, additional, Kern, Jens, additional, Hermes, Barbara, additional, Nachtkamp, Kathrin, additional, Panse, Jens Peter, additional, Sebastian, Martin, additional, Lehmann, Markus, additional, Wiewrodt, Rainer Gerhard, additional, Büttner, Reinhard, additional, Thomas, Roman K., additional, and Wolf, Juergen, additional

Published
2019
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18. BIOLUMA: A phase II trial of nivolumab in combination with ipilimumab to evaluate efficacy and safety in lung cancer and to evaluate biomarkers predictive for response—Preliminary results from the NSCLC cohort.

Author

Fischer, Rieke Nila, primary, George, Julie, additional, Scheel, Andreas H., additional, Schloesser, Hans Anton, additional, Vehreschild, Maria, additional, Brossart, Peter, additional, Engel-Riedel, Walburga, additional, Griesinger, Frank, additional, Grohé, Christian, additional, Kambartel, Karl-Otto, additional, Kern, Jens, additional, Hermes, Barbara, additional, Nachtkamp, Kathrin, additional, Panse, Jens Peter, additional, Sebastian, Martin, additional, Lehmann, Markus, additional, Wiewrodt, Rainer Gerhard, additional, Büttner, Reinhard, additional, Thomas, Roman K., additional, and Wolf, Juergen, additional

Published
2019
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19. Large cell neuroendocrine lung carcinoma induces peripheral T-cell repertoire alterations with predictive and prognostic significance

Author

Christopoulos, Petros, primary, Schneider, Marc A., additional, Bozorgmehr, Farastuk, additional, Kuon, Jonas, additional, Engel-Riedel, Walburga, additional, Kollmeier, Jens, additional, Baum, Volker, additional, Muley, Thomas, additional, Schnabel, Philipp A., additional, Bischoff, Helge, additional, Grohé, Christian, additional, Serke, Monika, additional, Thomas, Michael, additional, Fisch, Paul, additional, and Meister, Michael, additional

Published
2018
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20. 65Plus: open-label study of bevacizumab in combination with pemetrexed or pemetrexed/carboplatin as first-line treatment of patients with advanced or recurrent nonsquamous non-small-cell lung cancer

Author

Schuette, Wolfgang, primary, Schneider, Claus-Peter, additional, Engel-Riedel, Walburga, additional, Schumann, Christian, additional, Kohlhaeufl, Martin, additional, Serke, Monika, additional, Hoeffken, Gert, additional, Kortsik, Cornelius, additional, and Reck, Martin, additional

Published
2017
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22. P1.07-003 A Phase II Study Evaluating the Combination of Everolimus with Carboplatin/Paclitaxel as 1st Line Treatment in Patients with Advanced LCNEC

Author

Grohé, Christian, primary, Engel-Riedel, Walburga, additional, Kropf-Sanchen, Cornelia, additional, Joachim, Von Pawel, additional, Gütz, Sylvia, additional, Kollmeier, Jens, additional, Eberhardt, Wilfried, additional, Christopoulos, Petros, additional, Nimmrich, Inko, additional, Sieder, Christian, additional, Baum, Volker, additional, Serke, Monika, additional, and Thomas, Michael, additional

Published
2017
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23. MINI01.20: Interim Quality of Life (QoL) Results from ABOUND.sqm: nab -Paclitaxel/Carboplatin Induction Therapy in Squamous (SCC) NSCLC

Author

Thomas, Michael, primary, Page, Ray, additional, Gressot, Laurent, additional, Daniel, Davey, additional, Morgensztern, Daniel, additional, Levy, Benjamin, additional, Hussein, Maen, additional, Razaq, Mohammad, additional, Villaflor, Victoria M., additional, Aix, Santiago P., additional, Sivarajan, Kulumani, additional, Engel-Riedel, Walburga, additional, Staib, Peter, additional, Ko, Amy, additional, Ong, Teng J., additional, Trunova, Nataliya, additional, and Spigel, David R., additional

Published
2016
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24. Molecular Pathology and Personalized Medicine: The Dawn of a New Era in Companion Diagnostics-Practical Considerations about Companion Diagnostics for Non-Small-Cell-Lung-Cancer

Author

Ploenes, Till, Engel-Riedel, Walburga, Stoelben, Erich, Limmroth, Christina, Schildgen, Oliver, Schildgen, Verena, Ploenes, Till, Engel-Riedel, Walburga, Stoelben, Erich, Limmroth, Christina, Schildgen, Oliver, and Schildgen, Verena

Abstract

Companion diagnostics (CDx) have become a major tool in molecular pathology and assist in therapy decisions in an increasing number of various cancers. Particularly, the developments in lung cancer have been most impressing in the last decade and consequently lung cancer mutation testing and molecular profiling has become a major business of diagnostic laboratories. However, it has become difficult to decide which biomarkers are currently relevant for therapy decisions, as many of the new biomarkers are not yet approved as therapy targets, remain in the status of clinical studies, or still have not left the experimental phase. The current review is focussed on those markers that do have current therapy implications, practical implications arising from the respective companion diagnostics, and thus is focused on daily practice.

Published
2016

27. MET Amplification Status in Therapy-Naive Adeno- and Squamous Cell Carcinomas of the Lung

Author

Schildhaus, Hans-Ulrich, Schultheis, Anne M., Rueschoff, Josef, Binot, Elke, Merkelbach-Bruse, Sabine, Fassunke, Jana, Schulte, Wolfgang, Ko, Yon-Dschun, Schlesinger, Andreas, Bos, Marc, Gardizi, Masyar, Engel-Riedel, Walburga, Brockmann, Michael, Serke, Monika, Gerigk, Ulrich, Hekmat, Khosro, Frank, Konrad F., Reiser, Marcel, Schulz, Holger, Krueger, Stefan, Stoelben, Erich, Zander, Thomas, Wolf, Juergen, Buettner, Reinhard, Schildhaus, Hans-Ulrich, Schultheis, Anne M., Rueschoff, Josef, Binot, Elke, Merkelbach-Bruse, Sabine, Fassunke, Jana, Schulte, Wolfgang, Ko, Yon-Dschun, Schlesinger, Andreas, Bos, Marc, Gardizi, Masyar, Engel-Riedel, Walburga, Brockmann, Michael, Serke, Monika, Gerigk, Ulrich, Hekmat, Khosro, Frank, Konrad F., Reiser, Marcel, Schulz, Holger, Krueger, Stefan, Stoelben, Erich, Zander, Thomas, Wolf, Juergen, and Buettner, Reinhard

Abstract

Purpose: MET is a potential therapeutic target in lung cancer and both MET tyrosine kinase inhibitors and monoclonal antibodies have entered clinical trials. MET signaling can be activated by various mechanisms, including gene amplification. In this study, we aimed to investigate MET amplification status in adeno- and squamous cell carcinomas of the lung. We propose clearly defined amplification scores and provide epidemiologic data on MET amplification in lung cancer. Experimental Design: We evaluated the prevalence of increased MET gene copy numbers in 693 treatment-naive cancers by FISH, defined clear cutoff criteria, and correlated FISH results to MET IHC. Results: Two thirds (67%) of lung cancers do not have gains in MET gene copy numbers, whereas 3% show a clear-cut high-level amplification (MET/centromer7 ratio =2.0 or average gene copy number per nucleus =6.0 or =10% of tumor cells containing =15 MET copies). The remaining cases can be subdivided into intermediate- (6%) and low-level gains (24%). Importantly, MET amplifications occur at equal frequencies in squamous and adenocarcinomas without or with EGFR or KRAS mutations. Conclusion: MET amplification is not a mutually exclusive genetic event in therapy-naive non-small cell lung cancer. Our data suggest that it might be useful to determine MET amplification (i) before EGFR inhibitor treatment to identify possible primary resistance to anti-EGFR treatment, and (ii) to select cases that harbor KRAS mutations additionally to MET amplification and, thus, may not benefit from MET inhibition. Furthermore, our study provides comprehensive epidemiologic data for upcoming trials with various MET inhibitors. (C) 2014 AACR.

Published
2015

28. PIK3CA mutations in non-small cell lung cancer (NSCLC): Genetic heterogeneity, prognostic impact and incidence of prior malignancies

Author

Scheffler, Matthias, Bos, Marc, Gardizi, Masyar, Koenig, Katharina, Michels, Sebastian, Fassunke, Jana, Heydt, Carina, Kuenstlinger, Helen, Ihle, Michaela, Ueckeroth, Frank, Albus, Kerstin, Serke, Monika, Gerigk, Ulrich, Schulte, Wolfgang, Toepelt, Karin, Nogova, Lucia, Zander, Thomas, Engel-Riedel, Walburga, Stoelben, Erich, Ko, Yon-Dschun, Randerath, Winfried, Kaminsky, Britta, Panse, Jens, Becker, Carolin, Hellmich, Martin, Merkelbach-Bruse, Sabine, Heukamp, Lukas C., Buettner, Reinhard, Wolf, Juergen, Scheffler, Matthias, Bos, Marc, Gardizi, Masyar, Koenig, Katharina, Michels, Sebastian, Fassunke, Jana, Heydt, Carina, Kuenstlinger, Helen, Ihle, Michaela, Ueckeroth, Frank, Albus, Kerstin, Serke, Monika, Gerigk, Ulrich, Schulte, Wolfgang, Toepelt, Karin, Nogova, Lucia, Zander, Thomas, Engel-Riedel, Walburga, Stoelben, Erich, Ko, Yon-Dschun, Randerath, Winfried, Kaminsky, Britta, Panse, Jens, Becker, Carolin, Hellmich, Martin, Merkelbach-Bruse, Sabine, Heukamp, Lukas C., Buettner, Reinhard, and Wolf, Juergen

Abstract

Background: Somatic mutations of the PIK3CA gene have been described in non-small cell lung cancer (NSCLC), but limited data is available on their biological relevance. This study was performed to characterize PIK3CA-mutated NSCLC clinically and genetically. Patients and methods: Tumor tissue collected consecutively from 1144 NSCLC patients within a molecular screening network between March 2010 and March 2012 was analyzed for PIK3CA mutations using dideoxy-sequencing and next-generation sequencing (NGS). Clinical, pathological, and genetic characteristics of PIK3CA-mutated patients are described and compared with a control group of PIK3CA-wildtype patients. Results: Among the total cohort of 1144 patients we identified 42 (3.7%) patients with PIK3CA mutations in exon 9 and exon 20. These mutations were found with a higher frequency in sqamous cell carcinoma (8.9%) compared to adenocarcinoma (2.9%,p<0.001). The most common PIK3CA mutation was exon 9 E545K. The majority of patients (57.1%) had additional oncogenic driver aberrations. With the exception of EGFR-mutated patients, non of the genetically defined subgroups in this cohort had a significantly better median overall survival. Further, PIK3CA-mutated patients had a significantly higher incidence of malignancy prior to lung cancer (p<0.001). Conclusion: PIK3CA-mutated NSCLC represents a clinically and genetically heterogeneous subgroup in adenocarcinomas as well as in squamous cell carcinomas with a higher prevalence of these mutations in sqamous cell carcinoma. PIK3CA mutations have no negative impact on survival after surgery or systemic therapy. However, PIK3CA mutated lung cancer frequently develops in patients with prior malignancies.

Published
2015

29. A randomized Phase 2 study of pemetrexed in combination with cisplatin or carboplatin as adjuvant chemotherapy in patients with completely resected stage IB or II Non-Small-Cell Lung Cancer

Author

Schmid-Bindert, Gerald, primary, Engel-Riedel, Walburga, additional, Reck, Martin, additional, Schuette, Wolfgang, additional, Stöhlmacher, Jan, additional, Fischer, Jürgen R., additional, Mazières, Julien, additional, Chouaid, Christos, additional, Wolf, Martin, additional, Vinolas, Nuria, additional, Soldatenkova, Victoria, additional, Ripoche, Veronique, additional, Nguyen, Tuan, additional, and Visseren-Grul, Carla, additional

Published
2015
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30. Retrospektive Analyse von 99 Patienten mit einem neuroendokrinen Tumor der Lunge

Author

Ludwig, Corinna, Zimmermann, Johannes, Engel-Riedel, Walburga, Brockmann, Michael, and Steolben, Erich

Subjects
ddc: 610, 610 Medical sciences, Medicine
Abstract

Einleitung: Neuroendokrine Tumoren der Lunge werden unterteilt in das typische Karzinoid (TC), das atypische Karzinoid (AC), den neuroendokrinen Großzeller (LCNEC) und den Kleinzeller (SCLC). Den größten Anteil macht der Kleinzeller mit 20-25% aus. Im Gegensatz dazu sind Karzinoide[for full text, please go to the a.m. URL], 130. Kongress der Deutschen Gesellschaft für Chirurgie

Published
2013
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31. Radiation and Dose‐densification of R‐CHOP in Primary Mediastinal B‐cell Lymphoma: Subgroup Analysis of the UNFOLDER Trial.

Author

Held, Gerhard, Thurner, Lorenz, Poeschel, Viola, Ott, German, Schmidt, Christian, Christofyllakis, Konstantinos, Viardot, Andreas, Borchmann, Peter, Engel‐Riedel, Walburga, Frickhofen, Norbert, Nickelsen, Maike, Shpilberg, Ofer, Witzens‐Harig, Mathias, Griesinger, Frank, Krammer‐Steiner, Beate, Neubauer, Andreas, de Nully Brown, Peter, Federico, Massimo, Glass, Bertram, and Schmitz, Norbert

Published
2023
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32. Benchmarking of mutation diagnostics in clinical lung cancer specimens

Author

Querings, Silvia, Altmüller, Janine, Ansén, Sascha, Zander, Thomas, Seidel, Danila, Gabler, Franziska, Peifer, Martin, Markert, Eva, Stemshorn, Kathryn, Timmermann, Bernd, Saal, Beate, Klose, Stefan, Ernestus, Karen, Scheffler, Matthias, Engel-Riedel, Walburga, Stoelben, Erich, Brambilla, Elisabeth, Wolf, Jürgen, Nürnberg, Peter, and Thomas, Roman K.

Subjects
Adult, Male, Anatomy and Physiology, Clinical Pathology, Lung Neoplasms, DNA Mutational Analysis, Molecular Sequence Data, Histopathology, lcsh:Medicine, Endocrine System, Biochemistry, Lung and Intrathoracic Tumors, Genetic Mutation, Diagnostic Medicine, Growth Factors, Carcinoma, Non-Small-Cell Lung, Molecular Cell Biology, Tyrosine Kinase Signaling Cascade, Genetics, Pathology, Humans, lcsh:Science, Biology, Aged, Clinical Genetics, Endocrine Physiology, Base Sequence, Genome, Human, lcsh:R, Personalized Medicine, Proteins, Cancers and Neoplasms, Exons, Middle Aged, Signaling Cascades, Non-Small Cell Lung Cancer, ErbB Receptors, Benchmarking, Treatment Outcome, Oncology, Anatomical Pathology, Mutation, Medicine, Female, lcsh:Q, Research Article, Signal Transduction
Abstract

Treatment of EGFR-mutant non-small cell lung cancer patients with the tyrosine kinase inhibitors erlotinib or gefitinib results in high response rates and prolonged progression-free survival. Despite the development of sensitive mutation detection approaches, a thorough validation of these in a clinical setting has so far been lacking. We performed, in a clinical setting, a systematic validation of dideoxy 'Sanger' sequencing and pyrosequencing against massively parallel sequencing as one of the most sensitive mutation detection technologies available. Mutational annotation of clinical lung tumor samples revealed that of all patients with a confirmed response to EGFR inhibition, only massively parallel sequencing detected all relevant mutations. By contrast, dideoxy sequencing missed four responders and pyrosequencing missed two responders, indicating a dramatic lack of sensitivity of dideoxy sequencing, which is widely applied for this purpose. Furthermore, precise quantification of mutant alleles revealed a low correlation (r(2) = 0.27) of histopathological estimates of tumor content and frequency of mutant alleles, thereby questioning the use of histopathology for stratification of specimens for individual analytical procedures. Our results suggest that enhanced analytical sensitivity is critically required to correctly identify patients responding to EGFR inhibition. More broadly, our results emphasize the need for thorough evaluation of all mutation detection approaches against massively parallel sequencing as a prerequisite for any clinical implementation.

Published
2011

33. Durability and characteristics of objective tumor responses with the innate immune cell modulator Imprime PGG in combination with standard of care frontline treatment for patients (Pts) with metastatic non-squamous NSCLC.

Author

Engel-Riedel, Walburga, primary, Schneller, Folker, additional, Wolf, Martin, additional, Schuette, Wolfgang, additional, Ma, Mable, additional, Mattson, Paulette, additional, Lowe, Jamie R., additional, and Braun, Ada H., additional

Published
2015
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34. Safety of Imprime PGG, a novel innate immune cell modulator, in adults with stage IV non-small cell lung cancer: an integrated analysis of two randomized phase 2 studies.

Author

Schneller, Folker, primary, Engel-Riedel, Walburga, additional, Thomas, Michael, additional, Kollmeier, Jens, additional, Sadjadian, Parvis, additional, Wolf, Martin, additional, Schuette, Wolfgang, additional, Taitt, Corina Candiani, additional, Huhn, Richard Dale, additional, Ma, Mable, additional, Mattson, Paulette, additional, Lowe, Jamie R., additional, and Braun, Ada H., additional

Published
2015
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35. Final results from a Phase II study of pemetrexed and cisplatin with concurrent thoracic radiation after Pem-Cis induction in patients with unresectable locally advanced non-squamous non-small cell lung cancer (NSCLC)

Author

Garrido, Pilar, primary, Engel-Riedel, Walburga, additional, Serke, Monika, additional, Giraud, Philippe, additional, Ricardi, Umberto, additional, Vallejo, Carmen, additional, Visseren-Grul, Carla, additional, Ameryckx, Sophie, additional, Soldatenkova, Victoria, additional, Chouaki, Nadia, additional, and Novello, Silvia, additional

Published
2015
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36. MET Amplification Status in Therapy-Naïve Adeno- and Squamous Cell Carcinomas of the Lung

Author

Schildhaus, Hans-Ulrich, primary, Schultheis, Anne M., additional, Rüschoff, Josef, additional, Binot, Elke, additional, Merkelbach-Bruse, Sabine, additional, Fassunke, Jana, additional, Schulte, Wolfgang, additional, Ko, Yon-Dschun, additional, Schlesinger, Andreas, additional, Bos, Marc, additional, Gardizi, Masyar, additional, Engel-Riedel, Walburga, additional, Brockmann, Michael, additional, Serke, Monika, additional, Gerigk, Ulrich, additional, Hekmat, Khosro, additional, Frank, Konrad F., additional, Reiser, Marcel, additional, Schulz, Holger, additional, Krüger, Stefan, additional, Stoelben, Erich, additional, Zander, Thomas, additional, Wolf, Jürgen, additional, and Buettner, Reinhard, additional

Published
2015
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37. Clinical and molecular characteristics of non-small cell lung cancer patients harboring PIK3CA mutations.

Author

Michels, Sebastian Yves Friedrich, Scheffler, Matthias, Gardizi, Masyar, Christiaan, Marc, Bos, Allardt, Nogova, Lucia, Koenig, Katharine, Fassunke, Jana, Heydt, Carina, Michaela, Ihle, Kuenstlinger, Helen, Toepit, Karin, Ueckeroth, Frank, Albus, Kerstin, Serke, Monika Heidi, Randerath, Winfried, Engel-Riedel, Walburga, Merkelbach-Bruse, Sabine, Heukamp, Lukas Carl, Buettner, Reinhard, Wolf, Juergen, Michels, Sebastian Yves Friedrich, Scheffler, Matthias, Gardizi, Masyar, Christiaan, Marc, Bos, Allardt, Nogova, Lucia, Koenig, Katharine, Fassunke, Jana, Heydt, Carina, Michaela, Ihle, Kuenstlinger, Helen, Toepit, Karin, Ueckeroth, Frank, Albus, Kerstin, Serke, Monika Heidi, Randerath, Winfried, Engel-Riedel, Walburga, Merkelbach-Bruse, Sabine, Heukamp, Lukas Carl, Buettner, Reinhard, and Wolf, Juergen

Published
2014

38. Combined point mutation in KRAS or EGFR genes and EML4-ALK translocation in lung cancer patients

Author

Juergens, Jessica, Engel-Riedel, Walburga, Prickartz, Alexander, Ludwig, Corinna, Schildgen, Oliver, Tillmann, Ramona-Liza, Stoelben, Erich, Brockmann, Michael, Schildgen, Verena, Juergens, Jessica, Engel-Riedel, Walburga, Prickartz, Alexander, Ludwig, Corinna, Schildgen, Oliver, Tillmann, Ramona-Liza, Stoelben, Erich, Brockmann, Michael, and Schildgen, Verena

Abstract

A total of three cases with novel constellations regarding mutation patterns in non-small-cell lung cancer (NSCLC) are reported. The mutation patterns that are observed are novel and unexpected. First, a combined simultaneous KRAS mutation and EML4-ALK translocation, both in the main tumor and a bone metastasis, were observed, these mutations are assumed to mutually exclude each other. A further two cases include a father and a daughter, both of whom are suffering from NSCLC with different EGFR mutation patterns. A common cause was assumed; however, could not be deduced to mutations in the KRAS, BRAF and EGFR genes. The aforementioned cases are important, as it must be taken into account that mutations previously assumed to be exclusive can occur in combination, may influence the clinical outcome and may require different therapy compared with single mutated tumors. It has to be discussed whether diagnostic algorithms need to be adapted. The cases of father and daughter show that further unknown factors can influence development of NSCLC.

Published
2014

39. MIMEB: A phase II trial to evaluate FDG-PET/FLT-PET, DCE-MRI and molecular biomarkers for early prediction of nonprogression in patients with advanced non-small cell lung cancer treated with erlotinib and bevacizumab.

Author

Scheffier, Matthias, Boa, Marc Christiaan Allardt, Sos, Martin L., Heukamp, Lukas Carl, Nogova, Lucia, Koenig, Katharina, Gardizi, Masyar, Mattonet, Christian, Kahraman, Manz, Kobe, Ca, Boellaard, Ronald, Lammertsma, Adriaan A., Persigehl, Thorsten, Engel-Riedel, Walburga, Toepelt, Karin, Neumaier, Bernd, Buettner, Reinhard, Zander, Thomas, Wolf, Juergen, Scheffier, Matthias, Boa, Marc Christiaan Allardt, Sos, Martin L., Heukamp, Lukas Carl, Nogova, Lucia, Koenig, Katharina, Gardizi, Masyar, Mattonet, Christian, Kahraman, Manz, Kobe, Ca, Boellaard, Ronald, Lammertsma, Adriaan A., Persigehl, Thorsten, Engel-Riedel, Walburga, Toepelt, Karin, Neumaier, Bernd, Buettner, Reinhard, Zander, Thomas, and Wolf, Juergen

Published
2014

40. PIK3CA mutations in non-small cell lung cancer (NSCLC): Genetic heterogeneity, prognostic impact and incidence of prior malignancies

Author

Scheffler, Matthias, primary, Bos, Marc, additional, Gardizi, Masyar, additional, König, Katharina, additional, Michels, Sebastian, additional, Fassunke, Jana, additional, Heydt, Carina, additional, Künstlinger, Helen, additional, Ihle, Michaela, additional, Ueckeroth, Frank, additional, Albus, Kerstin, additional, Serke, Monika, additional, Gerigk, Ulrich, additional, Schulte, Wolfgang, additional, Töpelt, Karin, additional, Nogova, Lucia, additional, Zander, Thomas, additional, Engel-Riedel, Walburga, additional, Stoelben, Erich, additional, Ko, Yon-Dschun, additional, Randerath, Winfried, additional, Kaminsky, Britta, additional, Panse, Jens, additional, Becker, Carolin, additional, Hellmich, Martin, additional, Merkelbach-Bruse, Sabine, additional, Heukamp, Lukas C., additional, Büttner, Reinhard, additional, and Wolf, Jürgen, additional

Published
2014
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43. Clinical and molecular characteristics of non-small cell lung cancer patients harboring PIK3CA mutations.

Author

Michels, Sebastian Yves Friedrich, primary, Scheffler, Matthias, additional, Gardizi, Masyar, additional, Bos, Marc Christiaan Allardt, additional, Nogova, Lucia, additional, Koenig, Katharina, additional, Fassunke, Jana, additional, Heydt, Carina, additional, Michaela, Ihle, additional, Kuenstlinger, Helen, additional, Toepelt, Karin, additional, Ueckeroth, Frank, additional, Albus, Kerstin, additional, Serke, Monika Heidi, additional, Randerath, Winfried, additional, Engel-Riedel, Walburga, additional, Merkelbach-Bruse, Sabine, additional, Heukamp, Lukas Carl, additional, Buettner, Reinhard, additional, and Wolf, Juergen, additional

Published
2014
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45. Final overall survival (OS) results from a phase II study of pemetrexed (Pem) and cisplatin (Cis) with concurrent thoracic radiation (RT) after Pem-Cis induction in patients with unresectable locally advanced (LA) nonsquamous non-small cell lung cancer (NS-NSCLC).

Author

Novello, Silvia, primary, Engel-Riedel, Walburga, additional, Serke, Monika, additional, Giraud, Philippe, additional, Visseren-Grul, Carla, additional, Ameryckx, Sophie, additional, Soldatenkova, Victoria, additional, Chouaki, Nadia, additional, and Garrido, Pilar, additional

Published
2014
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46. MIMEB: A phase II trial to evaluate FDG-PET/FLT-PET, DCE-MRI and molecular biomarkers for early prediction of nonprogression in patients with advanced non-small cell lung cancer treated with erlotinib and bevacizumab.

Author

Scheffler, Matthias, primary, Bos, Marc Christiaan Allardt, additional, Sos, Martin L., additional, Heukamp, Lukas Carl, additional, Nogova, Lucia, additional, Koenig, Katharina, additional, Gardizi, Masyar, additional, Mattonet, Christian, additional, Kahraman, Deniz, additional, Kobe, Carsten, additional, Boellaard, Ronald, additional, Lammertsma, Adriaan A., additional, Persigehl, Thorsten, additional, Engel-Riedel, Walburga, additional, Toepelt, Karin, additional, Neumaier, Bernd, additional, Büttner, Reinhard, additional, Zander, Thomas, additional, and Wolf, Juergen, additional

Published
2014
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48. A Genomics-Based Classification of Human Lung Tumors

Author

Seidel, Danila, Zander, Thomas, Heukamp, Lukas C., Peifer, Martin, Bos, Marc, Fernandez-Cuesta, Lynnette, Leenders, Frauke, Lu, Xin, Ansen, Sascha, Gardizi, Masyar, Nguyen, Chau, Berg, Johannes, Russell, Prudence, Wainer, Zoe, Schildhaus, Hans-Ulrich, Rogers, Toni-Maree, Solomon, Benjamin, Pao, William, Carter, Scott L., Getz, Gad, Hayes, D. Neil, Wilkerson, Matthew D., Thunnissen, Erik, Travis, William D., Perner, Sven, Wright, Gavin, Brambilla, Elisabeth, Buettner, Reinhard, Wolf, Juergen, Thomas, Roman, Gabler, Franziska, Wilkening, Ines, Mueller, Christian, Dahmen, Ilona, Menon, Roopika, Koenig, Katharina, Albus, Kerstin, Merkelbach-Bruse, Sabine, Fassunke, Jana, Schmitz, Katja, Kuenstlinger, Helen, Kleine, Michaela, Binot, Elke, Querings, Silvia, Altmueller, Janine, Boessmann, Ingelore, Nuemberg, Peter, Schneider, Peter, Bogus, Magdalena, Soltermann, Alex, Moch, Holger, Brustugun, Odd Terje, Solberg, Steinar, Lund-Iversen, Marius, Helland, Aslaug, Muley, Thomas, Hoffmann, Hans, Schnabel, Philipp A., Chen, Yuan, Groen, Harry, Timens, Wim, Sietsma, Hannie, Clement, Joachim H., Weder, Walter, Saenger, Joerg, Stoelben, Erich, Ludwig, Corinna, Engel-Riedel, Walburga, Smit, Egbert, Heideman, Danille A. M., Snijders, Peter J. F., Nogova, Lucia, Sos, Martin L., Mattonet, Christian, Toepelt, Karin, Scheffler, Matthias, Goekkurt, Eray, Kappes, Rainer, Krueger, Stefan, Kambartel, Kato, Behringer, Dirk, Schulte, Wolfgang, Galetke, Wolfgang, Randerath, Winfried, Heldwein, Matthias, Schlesinger, Andreas, Serke, Monika, Hekmat, Khosro, Frank, Konrad F., Schnell, Roland, Reiser, Marcel, Huenerlituerkoglu, Ali-Nuri, Schmitz, Stephan, Meffert, Lisa, Ko, Yon-Dschun, Litt-Lampe, Markus, Gerigk, Ulrich, Fricke, Rainer, Besse, Benjamin, Brambilla, Christian, Lantuejoul, Sylvie, Lorimier, Philippe, Moro-Sibilot, Denis, Cappuzzo, Federico, Ligorio, Claudia, Damiani, Stefania, Field, John K., Hyde, Russell, Validire, Pierre, Girard, Philippe, Muscarella, Lucia A., Fazio, Vito M., Hallek, Michael, Soria, Jean-Charles, Achter, Viktor, Lang, Ulrich, Thomas, Roman K., Seidel, Danila, Zander, Thomas, Heukamp, Lukas C., Peifer, Martin, Bos, Marc, Fernandez-Cuesta, Lynnette, Leenders, Frauke, Lu, Xin, Ansen, Sascha, Gardizi, Masyar, Nguyen, Chau, Berg, Johannes, Russell, Prudence, Wainer, Zoe, Schildhaus, Hans-Ulrich, Rogers, Toni-Maree, Solomon, Benjamin, Pao, William, Carter, Scott L., Getz, Gad, Hayes, D. Neil, Wilkerson, Matthew D., Thunnissen, Erik, Travis, William D., Perner, Sven, Wright, Gavin, Brambilla, Elisabeth, Buettner, Reinhard, Wolf, Juergen, Thomas, Roman, Gabler, Franziska, Wilkening, Ines, Mueller, Christian, Dahmen, Ilona, Menon, Roopika, Koenig, Katharina, Albus, Kerstin, Merkelbach-Bruse, Sabine, Fassunke, Jana, Schmitz, Katja, Kuenstlinger, Helen, Kleine, Michaela, Binot, Elke, Querings, Silvia, Altmueller, Janine, Boessmann, Ingelore, Nuemberg, Peter, Schneider, Peter, Bogus, Magdalena, Soltermann, Alex, Moch, Holger, Brustugun, Odd Terje, Solberg, Steinar, Lund-Iversen, Marius, Helland, Aslaug, Muley, Thomas, Hoffmann, Hans, Schnabel, Philipp A., Chen, Yuan, Groen, Harry, Timens, Wim, Sietsma, Hannie, Clement, Joachim H., Weder, Walter, Saenger, Joerg, Stoelben, Erich, Ludwig, Corinna, Engel-Riedel, Walburga, Smit, Egbert, Heideman, Danille A. M., Snijders, Peter J. F., Nogova, Lucia, Sos, Martin L., Mattonet, Christian, Toepelt, Karin, Scheffler, Matthias, Goekkurt, Eray, Kappes, Rainer, Krueger, Stefan, Kambartel, Kato, Behringer, Dirk, Schulte, Wolfgang, Galetke, Wolfgang, Randerath, Winfried, Heldwein, Matthias, Schlesinger, Andreas, Serke, Monika, Hekmat, Khosro, Frank, Konrad F., Schnell, Roland, Reiser, Marcel, Huenerlituerkoglu, Ali-Nuri, Schmitz, Stephan, Meffert, Lisa, Ko, Yon-Dschun, Litt-Lampe, Markus, Gerigk, Ulrich, Fricke, Rainer, Besse, Benjamin, Brambilla, Christian, Lantuejoul, Sylvie, Lorimier, Philippe, Moro-Sibilot, Denis, Cappuzzo, Federico, Ligorio, Claudia, Damiani, Stefania, Field, John K., Hyde, Russell, Validire, Pierre, Girard, Philippe, Muscarella, Lucia A., Fazio, Vito M., Hallek, Michael, Soria, Jean-Charles, Achter, Viktor, Lang, Ulrich, and Thomas, Roman K.

Published
2013

49. Mapping the Hallmarks of Lung Adenocarcinoma with Massively Parallel Sequencing

Author

Imielinski, Marcin, Berger, Alice H., Hammerman, Peter S., Hernandez, Bryan, Pugh, Trevor J., Hodis, Eran, Cho, Jeonghee, Suh, James, Capelletti, Marzia, Sivachenko, Andrey, Sougnez, Carrie, Auclair, Daniel, Lawrence, Michael S., Stojanov, Petar, Cibulskis, Kristian, Choi, Kyusam, de Waal, Luc, Sharifnia, Tanaz, Brooks, Angela, Greulich, Heidi, Banerji, Shantanu, Zander, Thomas, Seidel, Danila, Leenders, Frauke, Ansen, Sascha, Ludwig, Corinna, Engel-Riedel, Walburga, Stoelben, Erich, Wolf, Juergen, Goparju, Chandra, Thompson, Kristin, Winckler, Wendy, Kwiatkowski, David, Johnson, Bruce E., Jaenne, Pasi A., Miller, Vincent A., Pao, William, Travis, William D., Pass, Harvey I., Gabriel, Stacey B., Lander, Eric S., Thomas, Roman K., Garraway, Levi A., Getz, Gad, Meyerson, Matthew, Imielinski, Marcin, Berger, Alice H., Hammerman, Peter S., Hernandez, Bryan, Pugh, Trevor J., Hodis, Eran, Cho, Jeonghee, Suh, James, Capelletti, Marzia, Sivachenko, Andrey, Sougnez, Carrie, Auclair, Daniel, Lawrence, Michael S., Stojanov, Petar, Cibulskis, Kristian, Choi, Kyusam, de Waal, Luc, Sharifnia, Tanaz, Brooks, Angela, Greulich, Heidi, Banerji, Shantanu, Zander, Thomas, Seidel, Danila, Leenders, Frauke, Ansen, Sascha, Ludwig, Corinna, Engel-Riedel, Walburga, Stoelben, Erich, Wolf, Juergen, Goparju, Chandra, Thompson, Kristin, Winckler, Wendy, Kwiatkowski, David, Johnson, Bruce E., Jaenne, Pasi A., Miller, Vincent A., Pao, William, Travis, William D., Pass, Harvey I., Gabriel, Stacey B., Lander, Eric S., Thomas, Roman K., Garraway, Levi A., Getz, Gad, and Meyerson, Matthew

Abstract

Lung adenocarcinoma, the most common subtype of non-small cell lung cancer, is responsible for more than 500,000 deaths per year worldwide. Here, we report exome and genome sequences of 183 lung adenocarcinoma tumor/normal DNA pairs. These analyses revealed a mean exonic somatic mutation rate of 12.0 events/megabase and identified the majority of genes previously reported as significantly mutated in lung adenocarcinoma. In addition, we identified statistically recurrent somatic mutations in the splicing factor gene U2AF1 and truncating mutations affecting RBM10 and ARID1A. Analysis of nucleotide context-specific mutation signatures grouped the sample set into distinct clusters that correlated with smoking history and alterations of reported lung adenocarcinoma genes. Whole-genome sequence analysis revealed frequent structural rearrangements, including in-frame exonic alterations within EGFR and SIK2 kinases. The candidate genes identified in this study are attractive targets for biological characterization and therapeutic targeting of lung adenocarcinoma.

Published
2012

50. Integrative genome analyses identify key somatic driver mutations of small-cell lung cancer

Author

Peifer, Martin, Fernandez-Cuesta, Lynnette, Sos, Martin L., George, Julie, Seidel, Danila, Kasper, Lawryn H., Plenker, Dennis, Leenders, Frauke, Sun, Ruping, Zander, Thomas, Menon, Roopika, Koker, Mirjam, Dahmen, Ilona, Mueller, Christian, Di Cerbo, Vincenzo, Schildhaus, Hans-Ulrich, Altmueller, Janine, Baessmann, Ingelore, Becker, Christian, de Wilde, Bram, Vandesompele, Jo, Boehm, Diana, Ansen, Sascha, Gabler, Franziska, Wilkening, Ines, Heynck, Stefanie, Heuckmann, Johannes M., Lu, Xin, Carter, Scott L., Cibulskis, Kristian, Banerji, Shantanu, Getz, Gad, Park, Kwon-Sik, Rauh, Daniel, Gruetter, Christian, Fischer, Matthias, Pasqualucci, Laura, Wright, Gavin, Wainer, Zoe, Russell, Prudence, Petersen, Iver, Chen, Yuan, Stoelben, Erich, Ludwig, Corinna, Schnabel, Philipp, Hoffmann, Hans, Muley, Thomas, Brockmann, Michael, Engel-Riedel, Walburga, Muscarella, Lucia A., Fazio, Vito M., Groen, Harry, Timens, Wim, Sietsma, Hannie, Thunnissen, Erik, Smit, Egbert, Heideman, Danielle A. M., Snijders, Peter J. F., Cappuzzo, Federico, Ligorio, Claudia, Damiani, Stefania, Field, John, Solberg, Steinar, Brustugun, Odd Terje, Lund-Iversen, Marius, Saenger, Joerg, Clement, Joachim H., Soltermann, Alex, Moch, Holger, Weder, Walter, Solomon, Benjamin, Soria, Jean-Charles, Validire, Pierre, Besse, Benjamin, Brambilla, Elisabeth, Brambilla, Christian, Lantuejoul, Sylvie, Lorimier, Philippe, Schneider, Peter M., Hallek, Michael, Pao, William, Meyerson, Matthew, Sage, Julien, Shendure, Jay, Schneider, Robert, Buettner, Reinhard, Wolf, Juergen, Nuernberg, Peter, Perner, Sven, Heukamp, Lukas C., Brindle, Paul K., Haas, Stefan, Thomas, Roman K., Peifer, Martin, Fernandez-Cuesta, Lynnette, Sos, Martin L., George, Julie, Seidel, Danila, Kasper, Lawryn H., Plenker, Dennis, Leenders, Frauke, Sun, Ruping, Zander, Thomas, Menon, Roopika, Koker, Mirjam, Dahmen, Ilona, Mueller, Christian, Di Cerbo, Vincenzo, Schildhaus, Hans-Ulrich, Altmueller, Janine, Baessmann, Ingelore, Becker, Christian, de Wilde, Bram, Vandesompele, Jo, Boehm, Diana, Ansen, Sascha, Gabler, Franziska, Wilkening, Ines, Heynck, Stefanie, Heuckmann, Johannes M., Lu, Xin, Carter, Scott L., Cibulskis, Kristian, Banerji, Shantanu, Getz, Gad, Park, Kwon-Sik, Rauh, Daniel, Gruetter, Christian, Fischer, Matthias, Pasqualucci, Laura, Wright, Gavin, Wainer, Zoe, Russell, Prudence, Petersen, Iver, Chen, Yuan, Stoelben, Erich, Ludwig, Corinna, Schnabel, Philipp, Hoffmann, Hans, Muley, Thomas, Brockmann, Michael, Engel-Riedel, Walburga, Muscarella, Lucia A., Fazio, Vito M., Groen, Harry, Timens, Wim, Sietsma, Hannie, Thunnissen, Erik, Smit, Egbert, Heideman, Danielle A. M., Snijders, Peter J. F., Cappuzzo, Federico, Ligorio, Claudia, Damiani, Stefania, Field, John, Solberg, Steinar, Brustugun, Odd Terje, Lund-Iversen, Marius, Saenger, Joerg, Clement, Joachim H., Soltermann, Alex, Moch, Holger, Weder, Walter, Solomon, Benjamin, Soria, Jean-Charles, Validire, Pierre, Besse, Benjamin, Brambilla, Elisabeth, Brambilla, Christian, Lantuejoul, Sylvie, Lorimier, Philippe, Schneider, Peter M., Hallek, Michael, Pao, William, Meyerson, Matthew, Sage, Julien, Shendure, Jay, Schneider, Robert, Buettner, Reinhard, Wolf, Juergen, Nuernberg, Peter, Perner, Sven, Heukamp, Lukas C., Brindle, Paul K., Haas, Stefan, and Thomas, Roman K.

Abstract

Small-cell lung cancer (SCLC) is an aggressive lung tumor subtype with poor prognosis(1-3). We sequenced 29 SCLC exomes, 2 genomes and 15 transcriptomes and found an extremely high mutation rate of 7.4 +/- 1 protein-changing mutations per million base pairs. Therefore, we conducted integrated analyses of the various data sets to identify pathogenetically relevant mutated genes. In all cases, we found evidence for inactivation of TP53 and RB1 and identified recurrent mutations in the CREBBP, EP300 and MLL genes that encode histone modifiers. Furthermore, we observed mutations in PTEN, SLIT2 and EPHA7, as well as focal amplifications of the FGFR1 tyrosine kinase gene. Finally, we detected many of the alterations found in humans in SCLC tumors from Tp53 and Rb1 double knockout mice(4). Our study implicates histone modification as a major feature of SCLC, reveals potentially therapeutically tractable genomic alterations and provides a generalizable framework for the identification of biologically relevant genes in the context of high mutational background.

Published
2012

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