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1. Corrigendum to 'Dissecting the genetic heterogeneity of gastric cancer'

Author

Timo Hess, Carlo Maj, Jan Gehlen, Oleg Borisov, Stephan L. Haas, Ines Gockel, Michael Vieth, Guillaume Piessen, Hakan Alakus, Yogesh Vashist, Carina Pereira, Michael Knapp, Vitalia Schüller, Alexander Quaas, Heike I. Grabsch, Jessica Trautmann, Ewa Malecka-Wojciesko, Anna Mokrowiecka, Jan Speller, Andreas Mayr, Julia Schröder, Axel M. Hillmer, Dominik Heider, Florian Lordick, Ángeles Pérez-Aísa, Rafael Campo, Jesús Espinel, Fernando Geijo, Concha Thomson, Luis Bujanda, Federico Sopeña, Ángel Lanas, María Pellisé, Claudia Pauligk, Thorsten Oliver Goetze, Carolin Zelck, Julian Reingruber, Emadeldin Hassanin, Peter Elbe, Sandra Alsabeah, Mats Lindblad, Magnus Nilsson, Nicole Kreuser, René Thieme, Francesca Tavano, Roberta Pastorino, Dario Arzani, Roberto Persiani, Jin-On Jung, Henrik Nienhüser, Katja Ott, Ralf R. Schumann, Oliver Kumpf, Susen Burock, Volker Arndt, Anna Jakubowska, Małgorzta Ławniczak, Victor Moreno, Vicente Martín, Manolis Kogevinas, Marina Pollán, Justyna Dąbrowska, Antonio Salas, Olivier Cussenot, Anne Boland-Auge, Delphine Daian, Jean-Francois Deleuze, Erika Salvi, Maris Teder-Laving, Gianluca Tomasello, Margherita Ratti, Chiara Senti, Valli De Re, Agostino Steffan, Arnulf H. Hölscher, Katharina Messerle, Christiane Josephine Bruns, Armands Sīviņš, Inga Bogdanova, Jurgita Skieceviciene, Justina Arstikyte, Markus Moehler, Hauke Lang, Peter P. Grimminger, Martin Kruschewski, Nikolaos Vassos, Claus Schildberg, Philipp Lingohr, Karsten Ridwelski, Hans Lippert, Nadine Fricker, Peter Krawitz, Per Hoffmann, Markus M. Nöthen, Lothar Veits, Jakob R. Izbicki, Adrianna Mostowska, Federico Martinón-Torres, Daniele Cusi, Rolf Adolfsson, Geraldine Cancel-Tassin, Aksana Höblinger, Ernst Rodermann, Monika Ludwig, Gisela Keller, Andres Metspalu, Hermann Brenner, Joerg Heller, Markus Neef, Michael Schepke, Franz Ludwig Dumoulin, Lutz Hamann, Renato Cannizzaro, Michele Ghidini, Dominik Plaßmann, Michael Geppert, Peter Malfertheiner, Olivier Glehen, Tomasz Skoczylas, Marek Majewski, Jan Lubiński, Orazio Palmieri, Stefania Boccia, Anna Latiano, Nuria Aragones, Thomas Schmidt, Mário Dinis-Ribeiro, Rui Medeiros, Salah-Eddin Al-Batran, Mārcis Leja, Juozas Kupcinskas, María A. García-González, Marino Venerito, and Johannes Schumacher

Subjects
Medicine, Medicine (General), R5-920
Published
2023
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2. Dissecting the genetic heterogeneity of gastric cancerResearch in context

Author

Timo Hess, Carlo Maj, Jan Gehlen, Oleg Borisov, Stephan L. Haas, Ines Gockel, Michael Vieth, Guillaume Piessen, Hakan Alakus, Yogesh Vashist, Carina Pereira, Michael Knapp, Vitalia Schüller, Alexander Quaas, Heike I. Grabsch, Jessica Trautmann, Ewa Malecka-Wojciesko, Anna Mokrowiecka, Jan Speller, Andreas Mayr, Julia Schröder, Axel M. Hillmer, Dominik Heider, Florian Lordick, Ángeles Pérez-Aísa, Rafael Campo, Jesús Espinel, Fernando Geijo, Concha Thomson, Luis Bujanda, Federico Sopeña, Ángel Lanas, María Pellisé, Claudia Pauligk, Thorsten Oliver Goetze, Carolin Zelck, Julian Reingruber, Emadeldin Hassanin, Peter Elbe, Sandra Alsabeah, Mats Lindblad, Magnus Nilsson, Nicole Kreuser, René Thieme, Francesca Tavano, Roberta Pastorino, Dario Arzani, Roberto Persiani, Jin-On Jung, Henrik Nienhüser, Katja Ott, Ralf R. Schumann, Oliver Kumpf, Susen Burock, Volker Arndt, Anna Jakubowska, Małgorzta Ławniczak, Victor Moreno, Vicente Martín, Manolis Kogevinas, Marina Pollán, Justyna Dąbrowska, Antonio Salas, Olivier Cussenot, Anne Boland-Auge, Delphine Daian, Jean-Francois Deleuze, Erika Salvi, Maris Teder-Laving, Gianluca Tomasello, Margherita Ratti, Chiara Senti, Valli De Re, Agostino Steffan, Arnulf H. Hölscher, Katharina Messerle, Christiane Josephine Bruns, Armands Sīviņš, Inga Bogdanova, Jurgita Skieceviciene, Justina Arstikyte, Markus Moehler, Hauke Lang, Peter P. Grimminger, Martin Kruschewski, Nikolaos Vassos, Claus Schildberg, Philipp Lingohr, Karsten Ridwelski, Hans Lippert, Nadine Fricker, Peter Krawitz, Per Hoffmann, Markus M. Nöthen, Lothar Veits, Jakob R. Izbicki, Adrianna Mostowska, Federico Martinón-Torres, Daniele Cusi, Rolf Adolfsson, Geraldine Cancel-Tassin, Aksana Höblinger, Ernst Rodermann, Monika Ludwig, Gisela Keller, Andres Metspalu, Hermann Brenner, Joerg Heller, Markus Neef, Michael Schepke, Franz Ludwig Dumoulin, Lutz Hamann, Renato Cannizzaro, Michele Ghidini, Dominik Plaßmann, Michael Geppert, Peter Malfertheiner, Olivier Gehlen, Tomasz Skoczylas, Marek Majewski, Jan Lubiński, Orazio Palmieri, Stefania Boccia, Anna Latiano, Nuria Aragones, Thomas Schmidt, Mário Dinis-Ribeiro, Rui Medeiros, Salah-Eddin Al-Batran, Mārcis Leja, Juozas Kupcinskas, María A. García-González, Marino Venerito, and Johannes Schumacher

Subjects
Gastric cancer, Oesophageal adenocarcinoma, Genome-wide association study (GWAS), Transcriptome-wide association study (TWAS), Medicine, Medicine (General), R5-920
Abstract

Summary: Background: Gastric cancer (GC) is clinically heterogenous according to location (cardia/non-cardia) and histopathology (diffuse/intestinal). We aimed to characterize the genetic risk architecture of GC according to its subtypes. Another aim was to examine whether cardia GC and oesophageal adenocarcinoma (OAC) and its precursor lesion Barrett’s oesophagus (BO), which are all located at the gastro-oesophageal junction (GOJ), share polygenic risk architecture. Methods: We did a meta-analysis of ten European genome-wide association studies (GWAS) of GC and its subtypes. All patients had a histopathologically confirmed diagnosis of gastric adenocarcinoma. For the identification of risk genes among GWAS loci we did a transcriptome-wide association study (TWAS) and expression quantitative trait locus (eQTL) study from gastric corpus and antrum mucosa. To test whether cardia GC and OAC/BO share genetic aetiology we also used a European GWAS sample with OAC/BO. Findings: Our GWAS consisting of 5816 patients and 10,999 controls highlights the genetic heterogeneity of GC according to its subtypes. We newly identified two and replicated five GC risk loci, all of them with subtype-specific association. The gastric transcriptome data consisting of 361 corpus and 342 antrum mucosa samples revealed that an upregulated expression of MUC1, ANKRD50, PTGER4, and PSCA are plausible GC-pathomechanisms at four GWAS loci. At another risk locus, we found that the blood-group 0 exerts protective effects for non-cardia and diffuse GC, while blood-group A increases risk for both GC subtypes. Furthermore, our GWAS on cardia GC and OAC/BO (10,279 patients, 16,527 controls) showed that both cancer entities share genetic aetiology at the polygenic level and identified two new risk loci on the single-marker level. Interpretation: Our findings show that the pathophysiology of GC is genetically heterogenous according to location and histopathology. Moreover, our findings point to common molecular mechanisms underlying cardia GC and OAC/BO. Funding: German Research Foundation (DFG).

Published
2023
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3. Overcoming EGFR G724S-mediated osimertinib resistance through unique binding characteristics of second-generation EGFR inhibitors

Author

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

Subjects
Science
Abstract

Acquired resistance to targeted drugs remains a major clinical challenge in lung adenocarcinoma patients. Here, the authors show how the acquired EGFR G724S mutation induces resistance to third-generation EGFR inhibitors and why the mutant kinase remains susceptible to second-generation inhibitors.

Published
2018
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4. Curative treatment in a patient with gastric cancer stage IV: a case report [v1; ref status: indexed, http://f1000r.es/S85RQ2]

Author

Andreas Diel, Ernst Rodermann, Hans-Friedrich Kienzle, Denis Meuthen, and Ingo Meuthen

Subjects
Cancer Therapeutics, Gastrointestinal Cancers, Medicine, Science
Abstract

A 39-year old patient with gastric adenocarcinoma stage IV failed to respond to preoperative chemotherapies containing 5-FU and cisplatin as well as 5-FU and irinotecan. After third-line chemotherapy with two cycles of docetaxel and cisplatin we confirmed a clinical partial response. A complete histologically confirmed remission was detected after complete resection of the tumor. Following two postoperative cycles of docetaxel and cisplatin, the tumor is still in complete remission after more than eight years.

Published
2012
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5. Curative treatment in a patient with gastric cancer stage IV: a case report [version 1; referees: 3 approved, 1 not approved]

Author

Andreas Diel, Ernst Rodermann, Hans-Friedrich Kienzle, Denis Meuthen, and Ingo Meuthen

Subjects
Case Report, Articles, Cancer Therapeutics, Gastrointestinal Cancers
Abstract

A 39-year old patient with gastric adenocarcinoma stage IV failed to respond to preoperative chemotherapies containing 5-FU and cisplatin as well as 5-FU and irinotecan. After third-line chemotherapy with two cycles of docetaxel and cisplatin we confirmed a clinical partial response. A complete histologically confirmed remission was detected after complete resection of the tumor. Following two postoperative cycles of docetaxel and cisplatin, the tumor is still in complete remission after more than eight years.

Published
2012
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