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237 results on '"Menon, Roopika"'

1. Somatic rearrangements causing oncogenic ectodomain deletions of FGFR1 in squamous cell lung cancer

Author

Malchers, Florian, Nogova, Lucia, van Attekum, Martijn H.A., Maas, Lukas, Bragelmann, Johannes, Bartenhagen, Christoph, Girard, Luc, Bosco, Graziella, Dahmen, Ilona, Michels, Sebastian, Weeden, Clare E., Scheel, Andreas H., Meder, Lydia, Golfmann, Kristina, Schuldt, Philipp, Siemanowski, Janna, Rehker, Jan, Merkelbach-Bruse, Sabine, Menon, Roopika, Gautschi, Oliver, Heuckmann, Johannes M., Brambilla, Elisabeth, Asselin-Labat, Marie-Liesse, Persigehl, Thorsten, Minna, John D., Walczak, Henning, Ullrich, Roland T., Fischer, Matthias, Reinhardt, Hans Christian, Wolf, Jurgen, Buttner, Reinhard, Peifer, Martin, George, Julie, and Thomas, Roman K.

Subjects
Thermo Fisher Scientific Inc., Pazopanib -- Health aspects, Lung cancer -- Genetic aspects -- Care and treatment, Health care industry
Abstract

The discovery of frequent 8p11-p12 amplifications in squamous cell lung cancer (SQLC) has fueled hopes that FGFR1, located inside this amplicon, might be a therapeutic target. In a clinical trial, only 11% of patients with 8p11 amplification (detected by FISH) responded to FGFR kinase inhibitor treatment. To understand the mechanism of FGFR1 dependency, we performed deep genomic characterization of 52 SQLCs with 8p11-p12 amplification, including 10 tumors obtained from patients who had been treated with FGFR inhibitors. We discovered somatically altered variants of FGFR1 with deletion of exons 1-8 that resulted from intragenic tail-to-tail rearrangements. These ectodomain-deficient FGFR1 variants ([DELTA]EC-FGFR1) were expressed in the affected tumors and were tumorigenic in both in vitro and in vivo models of lung cancer. Mechanistically, breakage-fusion-bridges were the source of 8p11-p12 amplification, resulting from frequent head-to-head and tail-to-tail rearrangements. Generally, tail-to-tail rearrangements within or in close proximity upstream of FGFR1 were associated with FGFR1 dependency. Thus, the genomic events shaping the architecture of the 8p11-p12 amplicon provide a mechanistic explanation for the emergence of FGFR1-driven SQLC. Specifically, we believe that FGFR1 ectodomain-deficient and FGFRI-centered amplifications caused by tail-to-tail rearrangements are a novel somatic genomic event that might be predictive of therapeutically relevant FGFR1 dependency., Introduction Squamous cell lung cancer (SQLC) is the second most common lung cancer subtype and among the cancers with the worst prognosis (1). Unfortunately, genetically activated kinase targets that provide [...]

Published
2023
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2. Integrative genomic profiling of large-cell neuroendocrine carcinomas reveals distinct subtypes of high-grade neuroendocrine lung tumors.

Author

George, Julie, Walter, Vonn, Peifer, Martin, Alexandrov, Ludmil B, Seidel, Danila, Leenders, Frauke, Maas, Lukas, Müller, Christian, Dahmen, Ilona, Delhomme, Tiffany M, Ardin, Maude, Leblay, Noemie, Byrnes, Graham, Sun, Ruping, De Reynies, Aurélien, McLeer-Florin, Anne, Bosco, Graziella, Malchers, Florian, Menon, Roopika, Altmüller, Janine, Becker, Christian, Nürnberg, Peter, Achter, Viktor, Lang, Ulrich, Schneider, Peter M, Bogus, Magdalena, Soloway, Matthew G, Wilkerson, Matthew D, Cun, Yupeng, McKay, James D, Moro-Sibilot, Denis, Brambilla, Christian G, Lantuejoul, Sylvie, Lemaitre, Nicolas, Soltermann, Alex, Weder, Walter, Tischler, Verena, Brustugun, Odd Terje, Lund-Iversen, Marius, Helland, Åslaug, Solberg, Steinar, Ansén, Sascha, Wright, Gavin, Solomon, Benjamin, Roz, Luca, Pastorino, Ugo, Petersen, Iver, Clement, Joachim H, Sänger, Jörg, Wolf, Jürgen, Vingron, Martin, Zander, Thomas, Perner, Sven, Travis, William D, Haas, Stefan A, Olivier, Magali, Foll, Matthieu, Büttner, Reinhard, Hayes, David Neil, Brambilla, Elisabeth, Fernandez-Cuesta, Lynnette, and Thomas, Roman K

Subjects
Humans, Neuroendocrine Tumors, Carcinoma, Neuroendocrine, Carcinoma, Non-Small-Cell Lung, Lung Neoplasms, Immunohistochemistry, In Situ Hybridization, Fluorescence, DNA Mutational Analysis, Genomics, Small Cell Lung Carcinoma, High-Throughput Nucleotide Sequencing, In Vitro Techniques, Carcinoma, Neuroendocrine, Non-Small-Cell Lung, In Situ Hybridization, Fluorescence
Abstract

Pulmonary large-cell neuroendocrine carcinomas (LCNECs) have similarities with other lung cancers, but their precise relationship has remained unclear. Here we perform a comprehensive genomic (n = 60) and transcriptomic (n = 69) analysis of 75 LCNECs and identify two molecular subgroups: "type I LCNECs" with bi-allelic TP53 and STK11/KEAP1 alterations (37%), and "type II LCNECs" enriched for bi-allelic inactivation of TP53 and RB1 (42%). Despite sharing genomic alterations with adenocarcinomas and squamous cell carcinomas, no transcriptional relationship was found; instead LCNECs form distinct transcriptional subgroups with closest similarity to SCLC. While type I LCNECs and SCLCs exhibit a neuroendocrine profile with ASCL1high/DLL3high/NOTCHlow, type II LCNECs bear TP53 and RB1 alterations and differ from most SCLC tumors with reduced neuroendocrine markers, a pattern of ASCL1low/DLL3low/NOTCHhigh, and an upregulation of immune-related pathways. In conclusion, LCNECs comprise two molecularly defined subgroups, and distinguishing them from SCLC may allow stratified targeted treatment of high-grade neuroendocrine lung tumors.

Published
2018

3. ALK alterations in salivary gland carcinomas

Author

Majewska, Hanna, Gorczyński, Adam, Czapiewski, Piotr, Menon, Roopika, Mueller, Judith, Lakis, Sotirios, Heuckmann, Johannes M., Laco, Jan, Gupta, Ruta, Andreasen, Simon, Stodulski, Dominik, Iliszko, Mariola, Dziadziuszko, Rafał, Jassem, Jacek, Heukamp, Lukas C., and Biernat, Wojciech

Published
2021
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4. A mechanistic classification of clinical phenotypes in neuroblastoma

Author

Ackermann, Sandra, Cartolano, Maria, Hero, Barbara, Welte, Anne, Kahlert, Yvonne, Roderwieser, Andrea, Bartenhagen, Christoph, Walter, Esther, Gecht, Judith, Kerschke, Laura, Volland, Ruth, Menon, Roopika, Heuckmann, Johannes M., Gartlgruber, Moritz, Hartlieb, Sabine, Henrich, Kai-Oliver, Okonechnikov, Konstantin, Altmüller, Janine, Nürnberg, Peter, Lefever, Steve, de Wilde, Bram, Sand, Frederik, Ikram, Fakhera, Rosswog, Carolina, Fischer, Janina, Theissen, Jessica, Hertwig, Falk, Singhi, Aatur D., Simon, Thorsten, Vogel, Wenzel, Perner, Sven, Krug, Barbara, Schmidt, Matthias, Rahmann, Sven, Achter, Viktor, Lang, Ulrich, Vokuhl, Christian, Ortmann, Monika, Büttner, Reinhard, Eggert, Angelika, Speleman, Frank, O’Sullivan, Roderick J., Thomas, Roman K., Berthold, Frank, Vandesompele, Jo, Schramm, Alexander, Westermann, Frank, Schulte, Johannes H., Peifer, Martin, and Fischer, Matthias

Published
2018

5. Comprehensive genomic profiles of small cell lung cancer

Author

George, Julie, Lim, Jing Shan, Jang, Se Jin, Cun, Yupeng, Ozretić, Luka, Kong, Gu, Leenders, Frauke, Lu, Xin, Fernández-Cuesta, Lynnette, Bosco, Graziella, Müller, Christian, Dahmen, Ilona, Jahchan, Nadine S, Park, Kwon-Sik, Yang, Dian, Karnezis, Anthony N, Vaka, Dedeepya, Torres, Angela, Wang, Maia Segura, Korbel, Jan O, Menon, Roopika, Chun, Sung-Min, Kim, Deokhoon, Wilkerson, Matt, Hayes, Neil, Engelmann, David, Pützer, Brigitte, Bos, Marc, Michels, Sebastian, Vlasic, Ignacija, Seidel, Danila, Pinther, Berit, Schaub, Philipp, Becker, Christian, Altmüller, Janine, Yokota, Jun, Kohno, Takashi, Iwakawa, Reika, Tsuta, Koji, Noguchi, Masayuki, Muley, Thomas, Hoffmann, Hans, Schnabel, Philipp A, Petersen, Iver, Chen, Yuan, Soltermann, Alex, Tischler, Verena, Choi, Chang-min, Kim, Yong-Hee, Massion, Pierre P, Zou, Yong, Jovanovic, Dragana, Kontic, Milica, Wright, Gavin M, Russell, Prudence A, Solomon, Benjamin, Koch, Ina, Lindner, Michael, Muscarella, Lucia A, la Torre, Annamaria, Field, John K, Jakopovic, Marko, Knezevic, Jelena, Castaños-Vélez, Esmeralda, Roz, Luca, Pastorino, Ugo, Brustugun, Odd-Terje, Lund-Iversen, Marius, Thunnissen, Erik, Köhler, Jens, Schuler, Martin, Botling, Johan, Sandelin, Martin, Sanchez-Cespedes, Montserrat, Salvesen, Helga B, Achter, Viktor, Lang, Ulrich, Bogus, Magdalena, Schneider, Peter M, Zander, Thomas, Ansén, Sascha, Hallek, Michael, Wolf, Jürgen, Vingron, Martin, Yatabe, Yasushi, Travis, William D, Nürnberg, Peter, Reinhardt, Christian, Perner, Sven, Heukamp, Lukas, Büttner, Reinhard, Haas, Stefan A, Brambilla, Elisabeth, Peifer, Martin, Sage, Julien, and Thomas, Roman K

Subjects
Biological Sciences, Biomedical and Clinical Sciences, Genetics, Oncology and Carcinogenesis, Human Genome, Cancer, Rare Diseases, Lung, Lung Cancer, Aetiology, 2.1 Biological and endogenous factors, Alleles, Animals, Cell Line, Tumor, Chromosome Breakpoints, Cyclin D1, DNA-Binding Proteins, Disease Models, Animal, Female, Gene Expression Profiling, Genome, Human, Genomics, Humans, Lung Neoplasms, Male, Mice, Mutation, Neurosecretory Systems, Nuclear Proteins, Receptors, Notch, Retinoblastoma Protein, Signal Transduction, Small Cell Lung Carcinoma, Tumor Protein p73, Tumor Suppressor Protein p53, Tumor Suppressor Proteins, General Science & Technology
Abstract

We have sequenced the genomes of 110 small cell lung cancers (SCLC), one of the deadliest human cancers. In nearly all the tumours analysed we found bi-allelic inactivation of TP53 and RB1, sometimes by complex genomic rearrangements. Two tumours with wild-type RB1 had evidence of chromothripsis leading to overexpression of cyclin D1 (encoded by the CCND1 gene), revealing an alternative mechanism of Rb1 deregulation. Thus, loss of the tumour suppressors TP53 and RB1 is obligatory in SCLC. We discovered somatic genomic rearrangements of TP73 that create an oncogenic version of this gene, TP73Δex2/3. In rare cases, SCLC tumours exhibited kinase gene mutations, providing a possible therapeutic opportunity for individual patients. Finally, we observed inactivating mutations in NOTCH family genes in 25% of human SCLC. Accordingly, activation of Notch signalling in a pre-clinical SCLC mouse model strikingly reduced the number of tumours and extended the survival of the mutant mice. Furthermore, neuroendocrine gene expression was abrogated by Notch activity in SCLC cells. This first comprehensive study of somatic genome alterations in SCLC uncovers several key biological processes and identifies candidate therapeutic targets in this highly lethal form of cancer.

Published
2015

6. Safety and Efficacy of Crizotinib in Patients With Advanced or Metastatic ROS1-Rearranged Lung Cancer (EUCROSS): A European Phase II Clinical Trial

Author

Michels, Sebastian, Massutí, Bartomeu, Schildhaus, Hans-Ulrich, Franklin, Jeremy, Sebastian, Martin, Felip, Enriqueta, Grohé, Christian, Rodriguez-Abreu, Delvys, Abdulla, Diana S.Y., Bischoff, Helge, Brandts, Christian, Carcereny, Enric, Corral, Jesús, Dingemans, Anne-Marie C., Pereira, Eva, Fassunke, Jana, Fischer, Rieke N., Gardizi, Masyar, Heukamp, Lukas, Insa, Amelia, Kron, Anna, Menon, Roopika, Persigehl, Thorsten, Reck, Martin, Riedel, Richard, Rothschild, Sacha I., Scheel, Andreas H., Scheffler, Matthias, Schmalz, Petra, Smit, Egbert F., Limburg, Meike, Provencio, Mariano, Karachaliou, Niki, Merkelbach-Bruse, Sabine, Hellmich, Martin, Nogova, Lucia, Büttner, Reinhard, Rosell, Rafael, and Wolf, Jürgen

Published
2019
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8. Data from CD74–NRG1 Fusions in Lung Adenocarcinoma

Author

Fernandez-Cuesta, Lynnette, primary, Plenker, Dennis, primary, Osada, Hirotaka, primary, Sun, Ruping, primary, Menon, Roopika, primary, Leenders, Frauke, primary, Ortiz-Cuaran, Sandra, primary, Peifer, Martin, primary, Bos, Marc, primary, Daßler, Juliane, primary, Malchers, Florian, primary, Schöttle, Jakob, primary, Vogel, Wenzel, primary, Dahmen, Ilona, primary, Koker, Mirjam, primary, Ullrich, Roland T., primary, Wright, Gavin M., primary, Russell, Prudence A., primary, Wainer, Zoe, primary, Solomon, Benjamin, primary, Brambilla, Elisabeth, primary, Nagy-Mignotte, Hélène, primary, Moro-Sibilot, Denis, primary, Brambilla, Christian G., primary, Lantuejoul, Sylvie, primary, Altmüller, Janine, primary, Becker, Christian, primary, Nürnberg, Peter, primary, Heuckmann, Johannes M., primary, Stoelben, Erich, primary, Petersen, Iver, primary, Clement, Joachim H., primary, Sänger, Jörg, primary, Muscarella, Lucia A., primary, la Torre, Annamaria, primary, Fazio, Vito M., primary, Lahortiga, Idoya, primary, Perera, Timothy, primary, Ogata, Souichi, primary, Parade, Marc, primary, Brehmer, Dirk, primary, Vingron, Martin, primary, Heukamp, Lukas C., primary, Buettner, Reinhard, primary, Zander, Thomas, primary, Wolf, Jürgen, primary, Perner, Sven, primary, Ansén, Sascha, primary, Haas, Stefan A., primary, Yatabe, Yasushi, primary, and Thomas, Roman K., primary

Published
2023
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9. Supplementary text from Genomic and Functional Fidelity of Small Cell Lung Cancer Patient-Derived Xenografts

Author

Drapkin, Benjamin J., primary, George, Julie, primary, Christensen, Camilla L., primary, Mino-Kenudson, Mari, primary, Dries, Ruben, primary, Sundaresan, Tilak, primary, Phat, Sarah, primary, Myers, David T., primary, Zhong, Jun, primary, Igo, Peter, primary, Hazar-Rethinam, Mehlika H., primary, Licausi, Joseph A., primary, Gomez-Caraballo, Maria, primary, Kem, Marina, primary, Jani, Kandarp N., primary, Azimi, Roxana, primary, Abedpour, Nima, primary, Menon, Roopika, primary, Lakis, Sotirios, primary, Heist, Rebecca S., primary, Büttner, Reinhard, primary, Haas, Stefan, primary, Sequist, Lecia V., primary, Shaw, Alice T., primary, Wong, Kwok-Kin, primary, Hata, Aaron N., primary, Toner, Mehmet, primary, Maheswaran, Shyamala, primary, Haber, Daniel A., primary, Peifer, Martin, primary, Dyson, Nicholas, primary, Thomas, Roman K., primary, and Farago, Anna F., primary

Published
2023
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10. Supplementary Tables from CD74–NRG1 Fusions in Lung Adenocarcinoma

Author

Fernandez-Cuesta, Lynnette, primary, Plenker, Dennis, primary, Osada, Hirotaka, primary, Sun, Ruping, primary, Menon, Roopika, primary, Leenders, Frauke, primary, Ortiz-Cuaran, Sandra, primary, Peifer, Martin, primary, Bos, Marc, primary, Daßler, Juliane, primary, Malchers, Florian, primary, Schöttle, Jakob, primary, Vogel, Wenzel, primary, Dahmen, Ilona, primary, Koker, Mirjam, primary, Ullrich, Roland T., primary, Wright, Gavin M., primary, Russell, Prudence A., primary, Wainer, Zoe, primary, Solomon, Benjamin, primary, Brambilla, Elisabeth, primary, Nagy-Mignotte, Hélène, primary, Moro-Sibilot, Denis, primary, Brambilla, Christian G., primary, Lantuejoul, Sylvie, primary, Altmüller, Janine, primary, Becker, Christian, primary, Nürnberg, Peter, primary, Heuckmann, Johannes M., primary, Stoelben, Erich, primary, Petersen, Iver, primary, Clement, Joachim H., primary, Sänger, Jörg, primary, Muscarella, Lucia A., primary, la Torre, Annamaria, primary, Fazio, Vito M., primary, Lahortiga, Idoya, primary, Perera, Timothy, primary, Ogata, Souichi, primary, Parade, Marc, primary, Brehmer, Dirk, primary, Vingron, Martin, primary, Heukamp, Lukas C., primary, Buettner, Reinhard, primary, Zander, Thomas, primary, Wolf, Jürgen, primary, Perner, Sven, primary, Ansén, Sascha, primary, Haas, Stefan A., primary, Yatabe, Yasushi, primary, and Thomas, Roman K., primary

Published
2023
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11. Data from Genomic and Functional Fidelity of Small Cell Lung Cancer Patient-Derived Xenografts

Author

Drapkin, Benjamin J., primary, George, Julie, primary, Christensen, Camilla L., primary, Mino-Kenudson, Mari, primary, Dries, Ruben, primary, Sundaresan, Tilak, primary, Phat, Sarah, primary, Myers, David T., primary, Zhong, Jun, primary, Igo, Peter, primary, Hazar-Rethinam, Mehlika H., primary, Licausi, Joseph A., primary, Gomez-Caraballo, Maria, primary, Kem, Marina, primary, Jani, Kandarp N., primary, Azimi, Roxana, primary, Abedpour, Nima, primary, Menon, Roopika, primary, Lakis, Sotirios, primary, Heist, Rebecca S., primary, Büttner, Reinhard, primary, Haas, Stefan, primary, Sequist, Lecia V., primary, Shaw, Alice T., primary, Wong, Kwok-Kin, primary, Hata, Aaron N., primary, Toner, Mehmet, primary, Maheswaran, Shyamala, primary, Haber, Daniel A., primary, Peifer, Martin, primary, Dyson, Nicholas, primary, Thomas, Roman K., primary, and Farago, Anna F., primary

Published
2023
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12. Supplementary Tables S3-S8 from Genomic and Functional Fidelity of Small Cell Lung Cancer Patient-Derived Xenografts

Author

Drapkin, Benjamin J., primary, George, Julie, primary, Christensen, Camilla L., primary, Mino-Kenudson, Mari, primary, Dries, Ruben, primary, Sundaresan, Tilak, primary, Phat, Sarah, primary, Myers, David T., primary, Zhong, Jun, primary, Igo, Peter, primary, Hazar-Rethinam, Mehlika H., primary, Licausi, Joseph A., primary, Gomez-Caraballo, Maria, primary, Kem, Marina, primary, Jani, Kandarp N., primary, Azimi, Roxana, primary, Abedpour, Nima, primary, Menon, Roopika, primary, Lakis, Sotirios, primary, Heist, Rebecca S., primary, Büttner, Reinhard, primary, Haas, Stefan, primary, Sequist, Lecia V., primary, Shaw, Alice T., primary, Wong, Kwok-Kin, primary, Hata, Aaron N., primary, Toner, Mehmet, primary, Maheswaran, Shyamala, primary, Haber, Daniel A., primary, Peifer, Martin, primary, Dyson, Nicholas, primary, Thomas, Roman K., primary, and Farago, Anna F., primary

Published
2023
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13. Supplementary Figures 1-11 from Genomic and Functional Fidelity of Small Cell Lung Cancer Patient-Derived Xenografts

Author

Drapkin, Benjamin J., primary, George, Julie, primary, Christensen, Camilla L., primary, Mino-Kenudson, Mari, primary, Dries, Ruben, primary, Sundaresan, Tilak, primary, Phat, Sarah, primary, Myers, David T., primary, Zhong, Jun, primary, Igo, Peter, primary, Hazar-Rethinam, Mehlika H., primary, Licausi, Joseph A., primary, Gomez-Caraballo, Maria, primary, Kem, Marina, primary, Jani, Kandarp N., primary, Azimi, Roxana, primary, Abedpour, Nima, primary, Menon, Roopika, primary, Lakis, Sotirios, primary, Heist, Rebecca S., primary, Büttner, Reinhard, primary, Haas, Stefan, primary, Sequist, Lecia V., primary, Shaw, Alice T., primary, Wong, Kwok-Kin, primary, Hata, Aaron N., primary, Toner, Mehmet, primary, Maheswaran, Shyamala, primary, Haber, Daniel A., primary, Peifer, Martin, primary, Dyson, Nicholas, primary, Thomas, Roman K., primary, and Farago, Anna F., primary

Published
2023
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14. Supplementary Figures from CD74–NRG1 Fusions in Lung Adenocarcinoma

Author

Fernandez-Cuesta, Lynnette, primary, Plenker, Dennis, primary, Osada, Hirotaka, primary, Sun, Ruping, primary, Menon, Roopika, primary, Leenders, Frauke, primary, Ortiz-Cuaran, Sandra, primary, Peifer, Martin, primary, Bos, Marc, primary, Daßler, Juliane, primary, Malchers, Florian, primary, Schöttle, Jakob, primary, Vogel, Wenzel, primary, Dahmen, Ilona, primary, Koker, Mirjam, primary, Ullrich, Roland T., primary, Wright, Gavin M., primary, Russell, Prudence A., primary, Wainer, Zoe, primary, Solomon, Benjamin, primary, Brambilla, Elisabeth, primary, Nagy-Mignotte, Hélène, primary, Moro-Sibilot, Denis, primary, Brambilla, Christian G., primary, Lantuejoul, Sylvie, primary, Altmüller, Janine, primary, Becker, Christian, primary, Nürnberg, Peter, primary, Heuckmann, Johannes M., primary, Stoelben, Erich, primary, Petersen, Iver, primary, Clement, Joachim H., primary, Sänger, Jörg, primary, Muscarella, Lucia A., primary, la Torre, Annamaria, primary, Fazio, Vito M., primary, Lahortiga, Idoya, primary, Perera, Timothy, primary, Ogata, Souichi, primary, Parade, Marc, primary, Brehmer, Dirk, primary, Vingron, Martin, primary, Heukamp, Lukas C., primary, Buettner, Reinhard, primary, Zander, Thomas, primary, Wolf, Jürgen, primary, Perner, Sven, primary, Ansén, Sascha, primary, Haas, Stefan A., primary, Yatabe, Yasushi, primary, and Thomas, Roman K., primary

Published
2023
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15. Supplementary Figures 1-5 from Mechanisms of Primary Drug Resistance in FGFR1-Amplified Lung Cancer

Author

Malchers, Florian, primary, Ercanoglu, Meryem, primary, Schütte, Daniel, primary, Castiglione, Roberta, primary, Tischler, Verena, primary, Michels, Sebastian, primary, Dahmen, Ilona, primary, Brägelmann, Johannes, primary, Menon, Roopika, primary, Heuckmann, Johannes M., primary, George, Julie, primary, Ansén, Sascha, primary, Sos, Martin L., primary, Soltermann, Alex, primary, Peifer, Martin, primary, Wolf, Jürgen, primary, Büttner, Reinhard, primary, and Thomas, Roman K., primary

Published
2023
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17. Clinical Impact of Immune Checkpoint Inhibitor (ICI) Response, DNA Damage Repair (DDR) Gene Mutations and Immune-Cell Infiltration in Metastatic Melanoma Subtypes

Author

Andrieu, Charlotte, primary, McNamee, Niamh, additional, Larkin, Anne-Marie, additional, Maguire, Alanna, additional, Menon, Roopika, additional, Mueller-Eisert, Judith, additional, Horgan, Noel, additional, Kennedy, Susan, additional, Gullo, Giuseppe, additional, Crown, John, additional, and Walsh, Naomi, additional

Published
2022
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18. ALKG1269A mutation as a potential mechanism of acquired resistance to crizotinib in an ALK-rearranged inflammatory myofibroblastic tumor

Author

Michels, Sebastian Y. F., Scheel, Andreas H., Wündisch, Thomas, Heuckmann, Johannes M., Menon, Roopika, Puesken, Michael, Kobe, Carsten, Pasternack, Helen, Heydt, Carina, Scheffler, Matthias, Fischer, Rieke, Schultheis, Anne M., Merkelbach-Bruse, Sabine, Heukamp, Lukas, Büttner, Reinhard, and Wolf, Jürgen

Published
2017
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20. Cell-free tumor DNA, CA125 and HE4 for the objective assessment of tumor burden in patients with advanced high-grade serous ovarian cancer

Author

Heitz, Florian, primary, Lakis, Sotirios, additional, Harter, Philipp, additional, Heikaus, Sebastian, additional, Sehouli, Jalid, additional, Talwar, Jatin, additional, Menon, Roopika, additional, Ataseven, Beyhan, additional, Bertrand, Miriam, additional, Schneider, Stephanie, additional, Mariotti, Erika, additional, Bommert, Mareike, additional, Müller, Judith N., additional, Prader, Sonia, additional, Leenders, Frauke, additional, Hengsbach, Alexandra, additional, Gloeckner, Christian, additional, Braicu, Elena Ioana, additional, Heukamp, Lukas C., additional, du Bois, Andreas, additional, and Heuckmann, Johannes M., additional

Published
2022
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21. Neuroblastoma Risk Assessment and Treatment Stratification with Hybrid Capture-Based Panel Sequencing

Author

Szymansky, Annabell, Kruetzfeldt, Louisa-Marie, Heukamp, Lukas C., Hertwig, Falk, Theissen, Jessica, Deubzer, Hedwig E., Willing, Eva-Maria, Menon, Roopika, Fuchs, Steffen, Thole, Theresa, Schulte, Stefanie, Schmelz, Karin, Künkele, Annette, Lang, Peter, Fuchs, Jörg, Eggert, Angelika, Eckert, Cornelia, Fischer, Matthias, Henssen, Anton G., Rodriguez-Fos, Elias, and Schulte, Johannes H.

Subjects
Cancer Research, NB-HCPS assay, MYCN, risk stratification, ALK, Article, targeted therapies, neuroblastoma, hybrid capture panel sequencing, Medicine, 600 Technik, Medizin, angewandte Wissenschaften::610 Medizin und Gesundheit::610 Medizin und Gesundheit
Abstract

For many years, the risk-based therapy stratification of children with neuroblastoma has relied on clinical and molecular covariates. In recent years, genome analysis has revealed further alterations defining risk, tumor biology, and therapeutic targets. The implementation of a robust and scalable method for analyzing traditional and new molecular markers in routine diagnostics is an urgent clinical need. Here, we investigated targeted panel sequencing as a diagnostic approach to analyze all relevant genomic neuroblastoma risk markers in one assay. Our “neuroblastoma hybrid capture sequencing panel” (NB-HCSP) assay employs a technology for the high-coverage sequencing (&gt, 1000×) of 55 selected genes and neuroblastoma-relevant genomic regions, which allows for the detection of single nucleotide changes, structural rearrangements, and copy number alterations. We validated our assay by analyzing 15 neuroblastoma cell lines and a cohort of 20 neuroblastomas, for which reference routine diagnostic data and genome sequencing data were available. We observed a high concordance for risk markers identified by the NB-HSCP assay, clinical routine diagnostics, and genome sequencing. Subsequently, we demonstrated clinical applicability of the NB-HCSP assay by analyzing routine clinical samples. We conclude that the NB-HCSP assay may be implemented into routine diagnostics as a single assay that covers all essential covariates for initial neuroblastoma classification, extended risk stratification, and targeted therapy selection.

Published
2021

29. ALK alterations in salivary gland carcinomas

Author

Majewska, Hanna, primary, Gorczyński, Adam, additional, Czapiewski, Piotr, additional, Menon, Roopika, additional, Mueller, Judith, additional, Lakis, Sotirios, additional, Heuckmann, Johannes M., additional, Laco, Jan, additional, Gupta, Ruta, additional, Andreasen, Simon, additional, Stodulski, Dominik, additional, Iliszko, Mariola, additional, Dziadziuszko, Rafał, additional, Jassem, Jacek, additional, Heukamp, Lukas C., additional, and Biernat, Wojciech, additional

Published
2020
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30. Integration of Tumor Mutation Burden and PD-L1 Testing in Routine Laboratory Diagnostics in Non-Small Cell Lung Cancer

Author

Schatz, Stefanie, primary, Falk, Markus, additional, Jóri, Balázs, additional, Ramdani, Hayat O., additional, Schmidt, Stefanie, additional, Willing, Eva-Maria, additional, Menon, Roopika, additional, Groen, Harry J. M., additional, Diehl, Linda, additional, Kröger, Matthias, additional, Wesseler, Claas, additional, Griesinger, Frank, additional, Hoffknecht, Petra, additional, Tiemann, Markus, additional, and Heukamp, Lukas C., additional

Published
2020
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31. Impact of Somatic Mutations on Outcome in Patients > 60 Years Old with Newly Diagnosed AML Treated with Response-Adapted Sequential Azacitidine and Induction Chemotherapy within the DRKS00004519 Trial (RAS-AZIC) of the East German Study Group of Hematology and Oncology (OSHO)

Author

Jaekel, Nadja, primary, Schulze, Susann, additional, Siebolts, Udo, additional, Haak, Anja, additional, Pazaitis, Nikolaos, additional, Cross, Michael, additional, Niederwieser, Dietger, additional, Hänel, Mathias, additional, Maschmeyer, Georg, additional, Wass, Maxi, additional, Heukamp, Lukas, additional, Menon, Roopika, additional, Bertrand, Miriam, additional, Wickenhauser, Claudia, additional, Brosteanu, Oana, additional, and Al-Ali, Haifa Kathrin, additional

Published
2019
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32. The HOPE fixation technique - a promising alternative to common prostate cancer biobanking approaches

Author

Braun Martin, Menon Roopika, Nikolov Pavel, Kirsten Robert, Petersen Karen, Schilling David, Schott Christina, Gündisch Sibylle, Fend Falko, Becker Karl-Friedrich, and Perner Sven

Subjects
HOPE technique, HOPE fixation, Prostate cancer, Neoplasms. Tumors. Oncology. Including cancer and carcinogens, RC254-282
Abstract

Abstract Background The availability of well-annotated prostate tissue samples through biobanks is key for research. Whereas fresh-frozen tissue is well suited for a broad spectrum of molecular analyses, its storage and handling is complex and cost-intensive. Formalin-fixed paraffin-embedded specimens (FFPE) are easy to handle and economic to store, but their applicability for molecular methods is restricted. The recently introduced Hepes-glutamic acid-buffer mediated Organic solvent Protection Effect (HOPE) is a promising alternative, which might have the potential to unite the benefits of FFPE and fresh-frozen specimen. Aim of the study was to compare HOPE-fixed, FFPE and fresh-frozen bio-specimens for their accessibility for diagnostic and research purposes. Methods 10 prostate cancer samples were each preserved with HOPE, formalin, and liquid nitrogen and studied with in-situ and molecular methods. Samples were H&E stained, and assessed by immunohistochemistry (i.e. PSA, GOLPH2, p63) and FISH (i.e. ERG rearrangement). We assessed DNA integrity by PCR, using control genes ranging from 100 to 600 bp amplicon size. RNA integrity was assessed through qRT-PCR on three housekeeping genes (TBP, GAPDH, β-actin). Protein expression was analysed by performing western blot analysis using GOLPH2 and PSA antibodies. Results Of the HOPE samples, morphologic quality of H&E sections, immunohistochemical staining, and the FISH assay was at least equal to FFPE tissue, and significantly better than the fresh-frozen specimens. DNA, RNA, and protein analysis of HOPE samples provided similar results as compared to fresh-frozen specimens. As expected, FFPE-samples were inferior for most of the molecular analyses. Conclusions This is the first study, comparatively assessing the suitability of these fixation methods for diagnostic and research utilization. Overall, HOPE-fixed bio-specimens combine the benefits of FFPE- and fresh-frozen samples. Results of this study have the potential to expand on contemporary prostate tissue biobanking approaches and can serve as a model for other organs and tumors.

Published
2011
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33. Structural Alterations of MET Trigger Response to MET Kinase Inhibition in Lung Adenocarcinoma Patients

Author

Plenker, Dennis, Bertrand, Miriam, de Langen, Adrianus J., Riedel, Richard, Lorenz, Carina, Scheel, Andreas H., Mueller, Judith, Braegelmann, Johannes, Dassler-Plenker, Juliane, Kobe, Carsten, Persigehl, Thorsten, Kluge, Alexander, Wurdinger, Thomas, Schellen, Pepijn, Hartmann, Gunther, Zacherle, Tobias, Menon, Roopika, Thunnissen, Erik, Buettner, Reinhard, Griesinger, Frank, Wolf, Juergen, Heukamp, Lukas, Sos, Martin L., Heuckmann, Johannes M., Plenker, Dennis, Bertrand, Miriam, de Langen, Adrianus J., Riedel, Richard, Lorenz, Carina, Scheel, Andreas H., Mueller, Judith, Braegelmann, Johannes, Dassler-Plenker, Juliane, Kobe, Carsten, Persigehl, Thorsten, Kluge, Alexander, Wurdinger, Thomas, Schellen, Pepijn, Hartmann, Gunther, Zacherle, Tobias, Menon, Roopika, Thunnissen, Erik, Buettner, Reinhard, Griesinger, Frank, Wolf, Juergen, Heukamp, Lukas, Sos, Martin L., and Heuckmann, Johannes M.

Abstract

Purpose: We sought to investigate the clinical response to MET inhibition in patients diagnosed with structural MET alterations and to characterize their functional relevance in cellular models. Experimental Design: Patients were selected for treatment with crizotinib upon results of hybrid capture-based next-generation sequencing. To confirm the clinical observations, we analyzed cellular models that express these MET kinase alterations. Results: Three individual patients were identified to harbor alterations within the MET receptor. Two patients showed genomic rearrangements, leading to a gene fusion of KIF5B or STARD3NL and MET. One patient diagnosed with an EML4-ALK rearrangement developed a MET kinase domain duplication as a resistance mechanism to ceritinib. All 3 patients showed a partial response to crizotinib that effectively inhibits MET and ALK among other kinases. The results were further confirmed using orthogonal cellular models. Conclusions: Crizotinib leads to a clinical response in patients with MET rearrangements. Our functional analyses together with the clinical data suggest that these structural alterations may represent actionable targets in lung cancer patients. (C) 2017 AACR.

Published
2018

34. Genomic and Functional Fidelity of Small Cell Lung Cancer Patient-Derived Xenografts

Author

Drapkin, Benjamin J., George, Julie, Christensen, Camilla L., Mino-Kenudson, Mari, Dries, Ruben, Sundaresan, Tilak, Phat, Sarah, Myers, David T., Zhong, Jun, Igo, Peter, Hazar-Rethinam, Mehlika H., Licausi, Joseph A., Gomez-Caraballo, Maria, Kem, Marina, Jani, Kandarp N., Azimi, Roxana, Abedpour, Nima, Menon, Roopika, Lakis, Sotirios, Heist, Rebecca S., Buettner, Reinhard, Haas, Stefan, Sequist, Lecia V., Shaw, Alice T., Wong, Kwok-Kin, Hata, Aaron N., Toner, Mehmet, Maheswaran, Shyamala, Haber, Daniel A., Peifer, Martin, Dyson, Nicholas, Thomas, Roman K., Farago, Anna F., Drapkin, Benjamin J., George, Julie, Christensen, Camilla L., Mino-Kenudson, Mari, Dries, Ruben, Sundaresan, Tilak, Phat, Sarah, Myers, David T., Zhong, Jun, Igo, Peter, Hazar-Rethinam, Mehlika H., Licausi, Joseph A., Gomez-Caraballo, Maria, Kem, Marina, Jani, Kandarp N., Azimi, Roxana, Abedpour, Nima, Menon, Roopika, Lakis, Sotirios, Heist, Rebecca S., Buettner, Reinhard, Haas, Stefan, Sequist, Lecia V., Shaw, Alice T., Wong, Kwok-Kin, Hata, Aaron N., Toner, Mehmet, Maheswaran, Shyamala, Haber, Daniel A., Peifer, Martin, Dyson, Nicholas, Thomas, Roman K., and Farago, Anna F.

Abstract

Small cell lung cancer (SCLC) patient-derived xenografts (PDX) can be generated from biopsies or circulating tumor cells (CTC), though scarcity of tissue and low efficiency of tumor growth have previously limited these approaches. Applying an established clinical-translational pipeline for tissue collection and an automated microfluidic platform for CTC enrichment, we generated 17 biopsy-derived PDXs and 17 CTC-derived PDXs in a 2-year timeframe, at 89% and 38% efficiency, respectively. Whole-exome sequencing showed that somatic alterations are stably maintained between patient tumors and PDXs. Early-passage PDXs maintain the genomic and transcriptional profiles of the founder PDX. In vivo treatment with etoposide and platinum (EP) in 30 PDX models demonstrated greater sensitivity in PDXs from EP-naive patients, and resistance to EP corresponded to increased expression of a MYC gene signature. Finally, serial CTC-derived PDXs generated from an individual patient at multiple time points accurately recapitulated the evolving drug sensitivities of that patient's disease. Collectively, this work highlights the translational potential of this strategy. SIGNIFICANCE: Effective translational research utilizing SCLC PDX models requires both efficient generation of models from patients and fidelity of those models in representing patient tumor characteristics. We present approaches for efficient generation of PDXs from both biopsies and CTCs, and demonstrate that these models capture the mutational landscape and functional features of the donor tumors. (C) 2018 AACR.

Published
2018

35. Mechanisms of primary drug resistance in FGFR1-amplified lung cancer

Author

Malchers, Florian, Ercanoglu, Meryem, Schütte, Daniel, Castiglione, Roberta, Tischler, Verena, Michels, Sebastian, Dahmen, Ilona, Brägelmann, Johannes, Menon, Roopika, Heuckmann, Johannes M, George, Julie, Ansén, Sascha, Sos, Martin L, Soltermann, Alex, Peifer, Martin, Wolf, Jürgen, Büttner, Reinhard, Thomas, Roman K, University of Zurich, and Thomas, Roman K

Subjects
10049 Institute of Pathology and Molecular Pathology, 610 Medicine & health, 2730 Oncology, 1306 Cancer Research
Published
2017

36. Genomic and Functional Fidelity of Small Cell Lung Cancer Patient-Derived Xenografts

Author

Drapkin, Benjamin J., primary, George, Julie, additional, Christensen, Camilla L., additional, Mino-Kenudson, Mari, additional, Dries, Ruben, additional, Sundaresan, Tilak, additional, Phat, Sarah, additional, Myers, David T., additional, Zhong, Jun, additional, Igo, Peter, additional, Hazar-Rethinam, Mehlika H., additional, Licausi, Joseph A., additional, Gomez-Caraballo, Maria, additional, Kem, Marina, additional, Jani, Kandarp N., additional, Azimi, Roxana, additional, Abedpour, Nima, additional, Menon, Roopika, additional, Lakis, Sotirios, additional, Heist, Rebecca S., additional, Büttner, Reinhard, additional, Haas, Stefan, additional, Sequist, Lecia V., additional, Shaw, Alice T., additional, Wong, Kwok-Kin, additional, Hata, Aaron N., additional, Toner, Mehmet, additional, Maheswaran, Shyamala, additional, Haber, Daniel A., additional, Peifer, Martin, additional, Dyson, Nicholas, additional, Thomas, Roman K., additional, and Farago, Anna F., additional

Published
2018
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37. Structural Alterations of MET Trigger Response to MET Kinase Inhibition in Lung Adenocarcinoma Patients

Author

Plenker, Dennis, primary, Bertrand, Miriam, additional, de Langen, Adrianus J., additional, Riedel, Richard, additional, Lorenz, Carina, additional, Scheel, Andreas H., additional, Müller, Judith, additional, Brägelmann, Johannes, additional, Daßler-Plenker, Juliane, additional, Kobe, Carsten, additional, Persigehl, Thorsten, additional, Kluge, Alexander, additional, Wurdinger, Thomas, additional, Schellen, Pepijn, additional, Hartmann, Gunther, additional, Zacherle, Tobias, additional, Menon, Roopika, additional, Thunnissen, Erik, additional, Büttner, Reinhard, additional, Griesinger, Frank, additional, Wolf, Jürgen, additional, Heukamp, Lukas, additional, Sos, Martin L., additional, and Heuckmann, Johannes M., additional

Published
2018
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38. Immunohistochemical, FISH and Genomic Profiling Study of Salivary Gland Carcinomas Reveals a Novel MYO18A-ALK Gene Rearrangement

Author

Majewska, Hanna, primary, Menon, Roopika, additional, Mueller, Judith, additional, Lakis, Sotirios, additional, Heuckmann, Johannes M, additional, Czapiewski, Piotr, additional, Gorczynski, Adam, additional, Andreansen, Simon, additional, Skalova, Alena, additional, Laco, Jan, additional, Gupta, Ruta, additional, Simpson, Roderick, additional, Stodulski, Dominik, additional, Iliszko, Mariola, additional, Dziadziuszko, Rafal, additional, Jassem, Jacek, additional, Heukamp, Lukas C, additional, and Biernat, Wojciech, additional

Published
2018
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39. Concordance between Comprehensive Cancer Genome Profiling in Plasma and Tumor Specimens

Author

Mueller, Judith N., Falk, Markus, Talwar, Jatin, Neemann, Nicole, Mariotti, Erika, Bertrand, Miriam, Zacherle, Tobias, Lakis, Sotirios, Menon, Roopika, Gloeckner, Christian, Tiemann, Markus, Heukamp, Lukas C., Thomas, Roman K., Griesinger, Frank, Heuckmann, Johannes M., Mueller, Judith N., Falk, Markus, Talwar, Jatin, Neemann, Nicole, Mariotti, Erika, Bertrand, Miriam, Zacherle, Tobias, Lakis, Sotirios, Menon, Roopika, Gloeckner, Christian, Tiemann, Markus, Heukamp, Lukas C., Thomas, Roman K., Griesinger, Frank, and Heuckmann, Johannes M.

Abstract

Introduction: Detection of somatic genomic alterations in the plasma of patients with cancer (liquid biopsy) are increasingly being used in the clinic. However, the concordance of alterations identified in liquid biopsies with those detected in cancer specimens is not routinely being determined. Methods: We sought to systematically compare alterations found by a massively parallel sequencing liquid biopsy assay covering 39 genes (NEOliquid [NEO New Oncology GmbH, Koln, Germany]) with those identified through routine diagnostic testing in a certified central pathology laboratory in a cohort of patients with nonsquamous NSCLC. NEOliquid is based on enrichment of the genomic territory of interest by hybrid capture and is thus capable of detecting point mutations, small insertions and deletions, copy number alterations, and gene rearrangements/fusions in a single assay. Results: In a cohort of 82 patients with matched blood/tissue samples, the concordance between NEOliquid and tissue-based routine testing was 98%, the sensitivity of NEOliquid was higher than 70%, and the specificity was 100%. Discordant cases included those with insufficient amounts of circulaating tumor DNA in plasma and cases in which known driver mutations (e.g., isocitrate dehydrogenase (NADP(+)), 1 systolic gene [IDH1] R132H, kinesin family member 5B gene [KIFSb-ret proto-oncogene [RET], or MNNG HOS Transforming gene [MET] exon 14) were found in the plasma but were not interrogated by routine tissue analyses. Conclusions: In summary, NEOliquid offers accurate and reliable detection of clinically relevant driver alterations in plasma of patients with cancer. (C) 2017 International Association for the Study of Lung Cancer. Published by Elsevier Inc. All rights reserved.

Published
2017

40. Mechanisms of Primary Drug Resistance in FGFR1-Amplified Lung Cancer

Author

Malchers, Florian, primary, Ercanoglu, Meryem, additional, Schütte, Daniel, additional, Castiglione, Roberta, additional, Tischler, Verena, additional, Michels, Sebastian, additional, Dahmen, Ilona, additional, Brägelmann, Johannes, additional, Menon, Roopika, additional, Heuckmann, Johannes M., additional, George, Julie, additional, Ansén, Sascha, additional, Sos, Martin L., additional, Soltermann, Alex, additional, Peifer, Martin, additional, Wolf, Jürgen, additional, Büttner, Reinhard, additional, and Thomas, Roman K., additional

Published
2017
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41. Cell-free tumor DNA in peri-operative blood samples from advanced high-grade serous ovarian cancer patients with and without complete resection.

Author

Heitz, Florian, primary, Lakis, Sotirios, additional, Harter, Philipp, additional, Sehouli, Jalid, additional, Talwar, Jatin, additional, Sprokmann, Mareike, additional, Bertrand, Miriam, additional, Ataseven, Beyhan, additional, Mariotti, Erika, additional, Schneider, Stephanie, additional, Müller, Judith N, additional, Menon, Roopika, additional, Prader, Sonia, additional, Leenders, Frauke, additional, Hengsbach, Alexandra, additional, Gloeckner, Christian, additional, Braicu, Elena Ioana, additional, Heukamp, Lukas C., additional, Heuckmann, Johannes, additional, and Du Bois, Andreas, additional

Published
2017
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42. Concordance between comprehensive cancer genome profiling in plasma and matched tumor specimens.

Author

Menon, Roopika, primary, Müller, Judith N, additional, Falk, Markus, additional, Lakis, Sotirios, additional, Mariotti, Erika, additional, Leenders, Frauke, additional, Bertrand, Miriam, additional, Neemann, Nicole, additional, Netchaeva, Maria, additional, Heukamp, Lukas C., additional, Gloeckner, Christian, additional, Tiemann, Markus, additional, Heuckmann, Johannes, additional, and Griesinger, Frank, additional

Published
2017
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43. ALK G1269A mutation as a potential mechanism of acquired resistance to crizotinib in an ALK-rearranged inflammatory myofibroblastic tumor

Author

Michels, Sebastian Y. F., primary, Scheel, Andreas H., additional, Wündisch, Thomas, additional, Heuckmann, Johannes M., additional, Menon, Roopika, additional, Puesken, Michael, additional, Kobe, Carsten, additional, Pasternack, Helen, additional, Heydt, Carina, additional, Scheffler, Matthias, additional, Fischer, Rieke, additional, Schultheis, Anne M., additional, Merkelbach-Bruse, Sabine, additional, Heukamp, Lukas, additional, Büttner, Reinhard, additional, and Wolf, Jürgen, additional

Published
2017
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47. Comprehensive genomic profiles of small cell lung cancer

Author

Menon, Roopika, Korbel, Jan O., Chun, Sung-Min, Park, Kwon-Sik, Yang, Dian, Jahchan, Nadine S., Wilkerson, Matt, Müller, Christian, Karnezis, Anthony N., Cun, Yupeng, Michels, Sebastian, Dahmen, Ilona, Kim, Deokhoon, Vlasic, Ignacija, Hayes, Neil, George, Julie, Pützer, Brigitte, Wang, Maia Segura, Pinther, Berit, Fernández-Cuesta, Lynnette, Leenders, Frauke, Vaka, Dedeepya, Engelmann, David, Ozretić, Luka, Kong, Gu, Torres, Angela, Jang, Se Jin, Seidel, Danila, Lu, Xin, Bosco, Graziella, Lim, Jing Shan, and Bos, Marc

Subjects
neoplasms, respiratory tract diseases
Abstract

We have sequenced the genomes of 110 small cell lung cancers (SCLC), one of the deadliest human cancers. In nearly all the tumours analysed we found bi-allelic inactivation of TP53 and RB1, sometimes by complex genomic rearrangements. Two tumours with wild-type RB1 had evidence of chromothripsis leading to overexpression of cyclin D1 (encoded by the CCND1 gene), revealing an alternative mechanism of Rb1 deregulation. Thus, loss of the tumour suppressors TP53 and RB1 is obligatory in SCLC. We discovered somatic genomic rearrangements of TP73 that create an oncogenic version of this gene, TP73Δex2/3. In rare cases, SCLC tumours exhibited kinase gene mutations, providing a possible therapeutic opportunity for individual patients. Finally, we observed inactivating mutations in NOTCH family genes in 25% of human SCLC. Accordingly, activation of Notch signalling in a pre-clinical SCLC mouse model strikingly reduced the number of tumours and extended the survival of the mutant mice. Furthermore, neuroendocrine gene expression was abrogated by Notch activity in SCLC cells. This first comprehensive study of somatic genome alterations in SCLC uncovers several key biological processes and identifies candidate therapeutic targets in this highly lethal form of cancer.

Published
2015
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48. Effectiveness of crizotinib in a patient with ALK IHC-positive/FISH-negative metastatic lung adenocarcinoma.

Author

UCL - SSS/IREC/MONT - Pôle Mont Godinne, UCL - (MGD) Service de pneumologie, UCL - SSS/IREC/MORF - Pôle de Morphologie, UCL - (MGD) Service d'anatomie pathologique, UCL - SSS/IREC/PNEU - Pôle de Pneumologie, ORL et Dermatologie, Rosoux, Adeline, Pauwels, Patrick, Duplaquet, Fabrice, D'Haene, Nicky, Weynand, Birgit, Delos, Monique, Menon, Roopika, Heukamp, Lukas Carl, Thunnissen, Erik, Ocak, Sebahat, UCL - SSS/IREC/MONT - Pôle Mont Godinne, UCL - (MGD) Service de pneumologie, UCL - SSS/IREC/MORF - Pôle de Morphologie, UCL - (MGD) Service d'anatomie pathologique, UCL - SSS/IREC/PNEU - Pôle de Pneumologie, ORL et Dermatologie, Rosoux, Adeline, Pauwels, Patrick, Duplaquet, Fabrice, D'Haene, Nicky, Weynand, Birgit, Delos, Monique, Menon, Roopika, Heukamp, Lukas Carl, Thunnissen, Erik, and Ocak, Sebahat

Abstract

We report a case of crizotinib effectiveness in a heavily pretreated patient with a metastatic NSCLC initially considered IHC-positive and FISH-negative for ALK rearrangement. After repeated analyses of tumor samples, borderline ALK FISH-positivity (18.5% positive cells) was demonstrated.

Published
2016

49. A Novel EGFR(C797) Variant Detected in a Pleural Biopsy Specimen from an Osimertinib-Treated Patient Using a Comprehensive Hybrid Capture-Based Next-Generation Sequencing Assay

Author

Menon, Roopika, Mueller, Judith, Schneider, Petra, Lakis, Sotirios, Thress, Kenneth, Wolf, Juergen, Heukamp, Lukas, Heuckmann, Johannes M., Griesinger, Frank, Menon, Roopika, Mueller, Judith, Schneider, Petra, Lakis, Sotirios, Thress, Kenneth, Wolf, Juergen, Heukamp, Lukas, Heuckmann, Johannes M., and Griesinger, Frank

Published
2016

50. Effectiveness of crizotinib in a patient with ALK IHC-positive/FISH-negative metastatic lung adenocarcinoma

Author

Rosoux, Adeline, Ocak, Sebahat, Pauwels, Patrick, Duplaquet, Fabrice, D'Haene, Nicky, Weynand, Birgit, Delos, Monique, Menon, Roopika, Heukamp, Lukas Carl Arl L.C., Thunnissen, Erik, Rosoux, Adeline, Ocak, Sebahat, Pauwels, Patrick, Duplaquet, Fabrice, D'Haene, Nicky, Weynand, Birgit, Delos, Monique, Menon, Roopika, Heukamp, Lukas Carl Arl L.C., and Thunnissen, Erik

Abstract

We report a case of crizotinib effectiveness in a heavily pretreated patient with a metastatic NSCLC initially considered IHC-positive and FISH-negative for ALK rearrangement. After repeated analyses of tumor samples, borderline ALK FISH-positivity (18.5% positive cells) was demonstrated., SCOPUS: ar.j, info:eu-repo/semantics/published

Published
2016

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