220 results on '"Mareschal, Sylvain"'
Search Results
2. Improving high-resolution copy number variation analysis from next generation sequencing using unique molecular identifiers
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Viailly, Pierre-Julien, Sater, Vincent, Viennot, Mathieu, Bohers, Elodie, Vergne, Nicolas, Berard, Caroline, Dauchel, Hélène, Lecroq, Thierry, Celebi, Alison, Ruminy, Philippe, Marchand, Vinciane, Lanic, Marie-Delphine, Dubois, Sydney, Penther, Dominique, Tilly, Hervé, Mareschal, Sylvain, and Jardin, Fabrice
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- 2021
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3. Identification of Somatic Mutations in Primary Cutaneous Diffuse Large B-Cell Lymphoma, Leg Type by Massive Parallel Sequencing
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Mareschal, Sylvain, Pham-Ledard, Anne, Viailly, Pierre Julien, Dubois, Sydney, Bertrand, Philippe, Maingonnat, Catherine, Fontanilles, Maxime, Bohers, Elodie, Ruminy, Philippe, Tournier, Isabelle, Courville, Philippe, Lenormand, Bernard, Duval, Anne Bénédicte, Andrieu, Emilie, Verneuil, Laurence, Vergier, Beatrice, Tilly, Hervé, Joly, Pascal, Frebourg, Thierry, Beylot-Barry, Marie, Merlio, Jean-Philippe, and Jardin, Fabrice
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- 2017
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4. Integrated transcriptomic and genomic analysis improves prediction of complete remission and survival in elderly patients with acute myeloid leukemia
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Österroos, Albin, Björklund, My, Eriksson, Anna, Lindberg, Johan, Nilsson, Christer, Mareschal, Sylvain, Rantalainen, Mattias, Grönberg, Henrik, and Lehmann, Sören
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- 2020
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5. Chronic T cell receptor stimulation unmasks NK receptor signaling in peripheral T cell lymphomas via epigenetic reprogramming
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Carras, Sylvain, Chartoire, Dimitri, Mareschal, Sylvain, Heiblig, Mael, Marcais, Antoine, Robinot, Remy, Urb, Mirjam, Pommier, Roxane M., Julia, Edith, Chebel, Amel, Verney, Aurelie, Bertheau, Charlotte, Bardel, Emilie, Fezelot, Caroline, Courtois, Lucien, Lours, Camille, Bouska, Alyssa, Sharma, Sunandini, Lefebvre, Christine, Rouault, Jean-Pierre, Sibon, David, Ferrari, Anthony, Iqbal, Javeed, de Leval, Laurence, Gaulard, Philippe, Traverse-Glehen, Alexandra, Sujobert, Pierre, Blery, Mathieu, Salles, Gilles, Walzer, Thierry, Bachy, Emmanuel, and Genestier, Laurent
- Subjects
Oncology, Experimental ,T cells -- Receptors ,Antigen receptors, T cell -- Health aspects -- Genetic aspects ,Non-Hodgkin's lymphomas -- Genetic aspects -- Development and progression ,Killer cells -- Health aspects -- Genetic aspects ,Cellular signal transduction -- Genetic aspects -- Health aspects ,Epigenetic inheritance -- Research ,Cancer -- Research ,Health care industry - Abstract
Peripheral T cell lymphomas (PTCLs) represent a significant unmet medical need with dismal clinical outcomes. The T cell receptor (TCR) is emerging as a key driver of T lymphocyte transformation. However, the role of chronic TCR activation in lymphomagenesis and in lymphoma cell survival is still poorly understood. Using a mouse model, we report that chronic TCR stimulation drove T cell lymphomagenesis, whereas TCR signaling did not contribute to PTCL survival. The combination of kinome, transcriptome, and epigenome analyses of mouse PTCLs revealed a NK cell-like reprogramming of PTCL cells with expression of NK receptors (NKRs) and downstream signaling molecules such as Tyrobp and SYK. Activating NKRs were functional in PTCLs and dependent on SYK activity. In vivo blockade of NKR signaling prolonged mouse survival, demonstrating the addiction of PTCLs to NKRs and downstream SYK/mTOR activity for their survival. We studied a large collection of human primary samples and identified several PTCLs recapitulating the phenotype described in this model by their expression of SYK and the NKR, suggesting a similar mechanism of lymphomagenesis and establishing a rationale for clinical studies targeting such molecules., Introduction Peripheral T cell lymphomas (PTCLs) are highly heterogenous, comprising at least 30 post-thymic (i.e., mature) T or NK cell-derived entities according to the current 2016 WHO classification (1). PTCLs [...]
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- 2021
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6. Supplementary Data from Biological and Clinical Relevance of Associated Genomic Alterations in MYD88 L265P and non-L265P–Mutated Diffuse Large B-Cell Lymphoma: Analysis of 361 Cases
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Dubois, Sydney, primary, Viailly, Pierre-Julien, primary, Bohers, Elodie, primary, Bertrand, Philippe, primary, Ruminy, Philippe, primary, Marchand, Vinciane, primary, Maingonnat, Catherine, primary, Mareschal, Sylvain, primary, Picquenot, Jean-Michel, primary, Penther, Dominique, primary, Jais, Jean-Philippe, primary, Tesson, Bruno, primary, Peyrouze, Pauline, primary, Figeac, Martin, primary, Desmots, Fabienne, primary, Fest, Thierry, primary, Haioun, Corinne, primary, Lamy, Thierry, primary, Copie-Bergman, Christiane, primary, Fabiani, Bettina, primary, Delarue, Richard, primary, Peyrade, Frédéric, primary, André, Marc, primary, Ketterer, Nicolas, primary, Leroy, Karen, primary, Salles, Gilles, primary, Molina, Thierry J., primary, Tilly, Hervé, primary, and Jardin, Fabrice, primary
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- 2023
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7. Table S5. Cohort variants. from Biological and Clinical Relevance of Associated Genomic Alterations in MYD88 L265P and non-L265P–Mutated Diffuse Large B-Cell Lymphoma: Analysis of 361 Cases
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Dubois, Sydney, primary, Viailly, Pierre-Julien, primary, Bohers, Elodie, primary, Bertrand, Philippe, primary, Ruminy, Philippe, primary, Marchand, Vinciane, primary, Maingonnat, Catherine, primary, Mareschal, Sylvain, primary, Picquenot, Jean-Michel, primary, Penther, Dominique, primary, Jais, Jean-Philippe, primary, Tesson, Bruno, primary, Peyrouze, Pauline, primary, Figeac, Martin, primary, Desmots, Fabienne, primary, Fest, Thierry, primary, Haioun, Corinne, primary, Lamy, Thierry, primary, Copie-Bergman, Christiane, primary, Fabiani, Bettina, primary, Delarue, Richard, primary, Peyrade, Frédéric, primary, André, Marc, primary, Ketterer, Nicolas, primary, Leroy, Karen, primary, Salles, Gilles, primary, Molina, Thierry J., primary, Tilly, Hervé, primary, and Jardin, Fabrice, primary
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- 2023
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8. Table S2. Cell of origin according to MYD88 mutations. from Biological and Clinical Relevance of Associated Genomic Alterations in MYD88 L265P and non-L265P–Mutated Diffuse Large B-Cell Lymphoma: Analysis of 361 Cases
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Dubois, Sydney, primary, Viailly, Pierre-Julien, primary, Bohers, Elodie, primary, Bertrand, Philippe, primary, Ruminy, Philippe, primary, Marchand, Vinciane, primary, Maingonnat, Catherine, primary, Mareschal, Sylvain, primary, Picquenot, Jean-Michel, primary, Penther, Dominique, primary, Jais, Jean-Philippe, primary, Tesson, Bruno, primary, Peyrouze, Pauline, primary, Figeac, Martin, primary, Desmots, Fabienne, primary, Fest, Thierry, primary, Haioun, Corinne, primary, Lamy, Thierry, primary, Copie-Bergman, Christiane, primary, Fabiani, Bettina, primary, Delarue, Richard, primary, Peyrade, Frédéric, primary, André, Marc, primary, Ketterer, Nicolas, primary, Leroy, Karen, primary, Salles, Gilles, primary, Molina, Thierry J., primary, Tilly, Hervé, primary, and Jardin, Fabrice, primary
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- 2023
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9. Supplementary Figure 4 from RNA Splicing Alterations Induce a Cellular Stress Response Associated with Poor Prognosis in Acute Myeloid Leukemia
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Anande, Govardhan, primary, Deshpande, Nandan P., primary, Mareschal, Sylvain, primary, Batcha, Aarif M.N., primary, Hampton, Henry R., primary, Herold, Tobias, primary, Lehmann, Soren, primary, Wilkins, Marc R., primary, Wong, Jason W.H., primary, Unnikrishnan, Ashwin, primary, and Pimanda, John E., primary
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- 2023
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10. Table S7. Immunohistochemical markers and gene rearrangements according to MYD88 variants. from Biological and Clinical Relevance of Associated Genomic Alterations in MYD88 L265P and non-L265P–Mutated Diffuse Large B-Cell Lymphoma: Analysis of 361 Cases
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Dubois, Sydney, primary, Viailly, Pierre-Julien, primary, Bohers, Elodie, primary, Bertrand, Philippe, primary, Ruminy, Philippe, primary, Marchand, Vinciane, primary, Maingonnat, Catherine, primary, Mareschal, Sylvain, primary, Picquenot, Jean-Michel, primary, Penther, Dominique, primary, Jais, Jean-Philippe, primary, Tesson, Bruno, primary, Peyrouze, Pauline, primary, Figeac, Martin, primary, Desmots, Fabienne, primary, Fest, Thierry, primary, Haioun, Corinne, primary, Lamy, Thierry, primary, Copie-Bergman, Christiane, primary, Fabiani, Bettina, primary, Delarue, Richard, primary, Peyrade, Frédéric, primary, André, Marc, primary, Ketterer, Nicolas, primary, Leroy, Karen, primary, Salles, Gilles, primary, Molina, Thierry J., primary, Tilly, Hervé, primary, and Jardin, Fabrice, primary
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- 2023
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11. Supplementary Figure 2 from RNA Splicing Alterations Induce a Cellular Stress Response Associated with Poor Prognosis in Acute Myeloid Leukemia
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Anande, Govardhan, primary, Deshpande, Nandan P., primary, Mareschal, Sylvain, primary, Batcha, Aarif M.N., primary, Hampton, Henry R., primary, Herold, Tobias, primary, Lehmann, Soren, primary, Wilkins, Marc R., primary, Wong, Jason W.H., primary, Unnikrishnan, Ashwin, primary, and Pimanda, John E., primary
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- 2023
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12. Supplementary Figure 3 from RNA Splicing Alterations Induce a Cellular Stress Response Associated with Poor Prognosis in Acute Myeloid Leukemia
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Anande, Govardhan, primary, Deshpande, Nandan P., primary, Mareschal, Sylvain, primary, Batcha, Aarif M.N., primary, Hampton, Henry R., primary, Herold, Tobias, primary, Lehmann, Soren, primary, Wilkins, Marc R., primary, Wong, Jason W.H., primary, Unnikrishnan, Ashwin, primary, and Pimanda, John E., primary
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- 2023
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13. Supplementary Data from Next-Generation Sequencing in Diffuse Large B-Cell Lymphoma Highlights Molecular Divergence and Therapeutic Opportunities: a LYSA Study
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Dubois, Sydney, primary, Viailly, Pierre-Julien, primary, Mareschal, Sylvain, primary, Bohers, Elodie, primary, Bertrand, Philippe, primary, Ruminy, Philippe, primary, Maingonnat, Catherine, primary, Jais, Jean-Philippe, primary, Peyrouze, Pauline, primary, Figeac, Martin, primary, Molina, Thierry J., primary, Desmots, Fabienne, primary, Fest, Thierry, primary, Haioun, Corinne, primary, Lamy, Thierry, primary, Copie-Bergman, Christiane, primary, Brière, Josette, primary, Petrella, Tony, primary, Canioni, Danielle, primary, Fabiani, Bettina, primary, Coiffier, Bertrand, primary, Delarue, Richard, primary, Peyrade, Frédéric, primary, Bosly, André, primary, André, Marc, primary, Ketterer, Nicolas, primary, Salles, Gilles, primary, Tilly, Hervé, primary, Leroy, Karen, primary, and Jardin, Fabrice, primary
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- 2023
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14. Supplementary Figure 1 from RNA Splicing Alterations Induce a Cellular Stress Response Associated with Poor Prognosis in Acute Myeloid Leukemia
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Anande, Govardhan, primary, Deshpande, Nandan P., primary, Mareschal, Sylvain, primary, Batcha, Aarif M.N., primary, Hampton, Henry R., primary, Herold, Tobias, primary, Lehmann, Soren, primary, Wilkins, Marc R., primary, Wong, Jason W.H., primary, Unnikrishnan, Ashwin, primary, and Pimanda, John E., primary
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- 2023
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15. Table S10. Clinical characteristics of patients with CNS relapse. from Biological and Clinical Relevance of Associated Genomic Alterations in MYD88 L265P and non-L265P–Mutated Diffuse Large B-Cell Lymphoma: Analysis of 361 Cases
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Dubois, Sydney, primary, Viailly, Pierre-Julien, primary, Bohers, Elodie, primary, Bertrand, Philippe, primary, Ruminy, Philippe, primary, Marchand, Vinciane, primary, Maingonnat, Catherine, primary, Mareschal, Sylvain, primary, Picquenot, Jean-Michel, primary, Penther, Dominique, primary, Jais, Jean-Philippe, primary, Tesson, Bruno, primary, Peyrouze, Pauline, primary, Figeac, Martin, primary, Desmots, Fabienne, primary, Fest, Thierry, primary, Haioun, Corinne, primary, Lamy, Thierry, primary, Copie-Bergman, Christiane, primary, Fabiani, Bettina, primary, Delarue, Richard, primary, Peyrade, Frédéric, primary, André, Marc, primary, Ketterer, Nicolas, primary, Leroy, Karen, primary, Salles, Gilles, primary, Molina, Thierry J., primary, Tilly, Hervé, primary, and Jardin, Fabrice, primary
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- 2023
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16. Table S1. Clinical and immunohistochemical data according to MYD88 mutation status. from Biological and Clinical Relevance of Associated Genomic Alterations in MYD88 L265P and non-L265P–Mutated Diffuse Large B-Cell Lymphoma: Analysis of 361 Cases
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Dubois, Sydney, primary, Viailly, Pierre-Julien, primary, Bohers, Elodie, primary, Bertrand, Philippe, primary, Ruminy, Philippe, primary, Marchand, Vinciane, primary, Maingonnat, Catherine, primary, Mareschal, Sylvain, primary, Picquenot, Jean-Michel, primary, Penther, Dominique, primary, Jais, Jean-Philippe, primary, Tesson, Bruno, primary, Peyrouze, Pauline, primary, Figeac, Martin, primary, Desmots, Fabienne, primary, Fest, Thierry, primary, Haioun, Corinne, primary, Lamy, Thierry, primary, Copie-Bergman, Christiane, primary, Fabiani, Bettina, primary, Delarue, Richard, primary, Peyrade, Frédéric, primary, André, Marc, primary, Ketterer, Nicolas, primary, Leroy, Karen, primary, Salles, Gilles, primary, Molina, Thierry J., primary, Tilly, Hervé, primary, and Jardin, Fabrice, primary
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- 2023
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17. Table S6. Cohort copy number variations. from Biological and Clinical Relevance of Associated Genomic Alterations in MYD88 L265P and non-L265P–Mutated Diffuse Large B-Cell Lymphoma: Analysis of 361 Cases
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Dubois, Sydney, primary, Viailly, Pierre-Julien, primary, Bohers, Elodie, primary, Bertrand, Philippe, primary, Ruminy, Philippe, primary, Marchand, Vinciane, primary, Maingonnat, Catherine, primary, Mareschal, Sylvain, primary, Picquenot, Jean-Michel, primary, Penther, Dominique, primary, Jais, Jean-Philippe, primary, Tesson, Bruno, primary, Peyrouze, Pauline, primary, Figeac, Martin, primary, Desmots, Fabienne, primary, Fest, Thierry, primary, Haioun, Corinne, primary, Lamy, Thierry, primary, Copie-Bergman, Christiane, primary, Fabiani, Bettina, primary, Delarue, Richard, primary, Peyrade, Frédéric, primary, André, Marc, primary, Ketterer, Nicolas, primary, Leroy, Karen, primary, Salles, Gilles, primary, Molina, Thierry J., primary, Tilly, Hervé, primary, and Jardin, Fabrice, primary
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- 2023
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18. Supplementary Figures from Biological and Clinical Relevance of Associated Genomic Alterations in MYD88 L265P and non-L265P–Mutated Diffuse Large B-Cell Lymphoma: Analysis of 361 Cases
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Dubois, Sydney, primary, Viailly, Pierre-Julien, primary, Bohers, Elodie, primary, Bertrand, Philippe, primary, Ruminy, Philippe, primary, Marchand, Vinciane, primary, Maingonnat, Catherine, primary, Mareschal, Sylvain, primary, Picquenot, Jean-Michel, primary, Penther, Dominique, primary, Jais, Jean-Philippe, primary, Tesson, Bruno, primary, Peyrouze, Pauline, primary, Figeac, Martin, primary, Desmots, Fabienne, primary, Fest, Thierry, primary, Haioun, Corinne, primary, Lamy, Thierry, primary, Copie-Bergman, Christiane, primary, Fabiani, Bettina, primary, Delarue, Richard, primary, Peyrade, Frédéric, primary, André, Marc, primary, Ketterer, Nicolas, primary, Leroy, Karen, primary, Salles, Gilles, primary, Molina, Thierry J., primary, Tilly, Hervé, primary, and Jardin, Fabrice, primary
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- 2023
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19. HACE1 is a putative tumor suppressor gene in B-cell lymphomagenesis and is down-regulated by both deletion and epigenetic alterations
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Bouzelfen, Abdelilah, Alcantara, Marion, Kora, Hafid, Picquenot, Jean-Michel, Bertrand, Philippe, Cornic, Marie, Mareschal, Sylvain, Bohers, Elodie, Maingonnat, Catherine, Ruminy, Philippe, Adriouch, Sahil, Boyer, Olivier, Dubois, Sydney, Bastard, Christian, Tilly, Hervé, Latouche, Jean-Baptiste, and Jardin, Fabrice
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- 2016
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20. The gene expression profile of inflammatory, hypoxic and metabolic genes predicts the metastatic spread of human head and neck squamous cell carcinoma
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Clatot, Florian, Gouérant, Sophie, Mareschal, Sylvain, Cornic, Marie, Berghian, Anca, Choussy, Olivier, El Ouakif, Faissal, François, Arnaud, Bénard, Magalie, Ruminy, Philippe, Picquenot, Jean-Michel, and Jardin, Fabrice
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- 2014
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21. Mediation analysis reveals common mechanisms of RUNX1 point mutations and RUNX1/RUNX1T1 fusions influencing survival of patients with acute myeloid leukemia
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Hornung, Roman, Jurinovic, Vindi, Batcha, Aarif M. N., Bamopoulos, Stefanos A., Rothenberg-Thurley, Maja, Amler, Susanne, Sauerland, Maria Cristina, Berdel, Wolfgang E., Wörmann, Bernhard J., Bohlander, Stefan K., Braess, Jan, Hiddemann, Wolfgang, Lehmann, Sören, Mareschal, Sylvain, Spiekermann, Karsten, Metzeler, Klaus H., Herold, Tobias, and Boulesteix, Anne-Laure
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- 2018
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22. Oncogenic events rather than antigen selection pressure may be the main driving forces for relapse in diffuse large B‐cell lymphomas
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Rizzo, David, Viailly, Pierre‐Julien, Mareschal, Sylvain, Bohers, Elodie, Picquenot, Jean‐Michel, Penther, Dominique, Dubois, Sydney, Marchand, Vinciane, Bertrand, Philippe, Maingonnat, Catherine, Etancelin, Pascaline, Feuillard, Jean, Bastard, Christian, Tilly, Hervé, Jardin, Fabrice, and Ruminy, Philippe
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- 2017
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23. PET/CT before autologous stem cell transplantation predicts outcome in refractory/relapsed follicular lymphoma
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Alcantara, Marion, Dupuis, Jehan, Mareschal, Sylvain, Julian, Anne, Cottereau, Anne Ségolène, Becker, Stéphanie, Dubois, Sydney, Oberic, Lucie, Huynh, Anne, Meignan, Michel, Laurent, Guy, Tilly, Hervé, Haioun, Corinne, and Ysebaert, Loïc
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- 2015
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24. Chromatin Accessibility Profiling to Increase Diagnostic Accuracy and Refine Cell-of-Origin Classification of Mature T-Cell Lymphomas
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Julia, Edith, primary, Mareschal, Sylvain, additional, Chebel, Amel, additional, Golfier, Camille, additional, Müller, Tony Andreas, additional, Lours, Camille, additional, Hadj-Hamou, Sofiane, additional, Bissay, Nathalie, additional, Tschanz, Manon, additional, Ceribelli, Michele, additional, Chartoire, Dimitri, additional, Vernay, Aurélie, additional, Carras, Sylvain, additional, Sibon, David, additional, Marçais, Ambroise, additional, Laurent, Camille, additional, Martin, Laurent, additional, Asnafi, Vahid, additional, Payen, Lea, additional, Sanlaville, Damien, additional, Bardel-Danjean, Claire, additional, Roussel, Mikael, additional, Szablewski, Vanessa, additional, Drieux, Fanny, additional, Ruminy, Philippe, additional, Herling, Marco, additional, Chassagne-Clément, Catherine, additional, Salles, Gilles, additional, Sujobert, Pierre, additional, Traverse-Glehen, Alexandra, additional, Baseggio, Lucile, additional, De Leval, Laurence, additional, Staudt, Louis M., additional, Gaulard, Philippe, additional, Genestier, Laurent, additional, and Bachy, Emmanuel, additional
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- 2021
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25. Outcome of patients older than 60 years with classical Hodgkin lymphoma treated with front line ABVD chemotherapy: frequent pulmonary events suggest limiting the use of bleomycin in the elderly
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Stamatoullas, Aspasia, Brice, Pauline, Bouabdallah, Reda, Mareschal, Sylvain, Camus, Vincent, Rahal, Ilhem, Franchi, Patricia, Lanic, Hélène, and Tilly, Hervé
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- 2015
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26. Additional file 1 of Improving high-resolution copy number variation analysis from next generation sequencing using unique molecular identifiers
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Viailly, Pierre-Julien, Sater, Vincent, Viennot, Mathieu, Bohers, Elodie, Vergne, Nicolas, Berard, Caroline, Dauchel, Hélène, Lecroq, Thierry, Celebi, Alison, Ruminy, Philippe, Marchand, Vinciane, Marie-Delphine Lanic, Dubois, Sydney, Penther, Dominique, Tilly, Hervé, Mareschal, Sylvain, and Jardin, Fabrice
- Abstract
Additional file 1. Supplementary Figures S1–S5, Supplementary Tables S1–S3.
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- 2021
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27. Rgb: a scriptable genome browser for R
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Mareschal, Sylvain, Dubois, Sydney, Lecroq, Thierry, and Jardin, Fabrice
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- 2014
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28. RNA Splicing Alterations Induce a Cellular Stress Response Associated with Poor Prognosis in Acute Myeloid Leukemia
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Anande, Govardhan, Deshpande, Nandan P., Mareschal, Sylvain, Batcha, Aarif M. N., Hampton, Henry R., Herold, Tobias, Lehmann, Sören, Wilkins, Marc R., Wong, Jason W. H., Unnikrishnan, Ashwin, Pimanda, John E., Anande, Govardhan, Deshpande, Nandan P., Mareschal, Sylvain, Batcha, Aarif M. N., Hampton, Henry R., Herold, Tobias, Lehmann, Sören, Wilkins, Marc R., Wong, Jason W. H., Unnikrishnan, Ashwin, and Pimanda, John E.
- Abstract
Purpose: RNA splicing is a fundamental biological process that generates protein diversity from a finite set of genes. Recurrent somatic mutations of splicing factor genes are common in some hematologic cancers but are relatively uncommon in acute myeloid leukemia (AML, < 20% of patients). We examined whether RNA splicing differences exist in AML, even in the absence of splicing factor mutations. Experimental Design: We developed a bioinformatics pipeline to study alternative RNA splicing in RNA-sequencing data from large cohorts of patients with AML. Results: We have identified recurrent differential alternative splicing between patients with poor and good prognosis. These splicing events occurred even in patients without any discernible splicing factor mutations. Alternative splicing recurrently occurred in genes with specific molecular functions, primarily related to protein translation. Developing tools to predict the functional impact of alternative splicing on the translated protein, we discovered that approximately 45% of the splicing events directly affected highly conserved protein domains. Several splicing factors were themselves misspliced and the splicing of their target transcripts were altered. Studying differential gene expression in the same patients, we identified that alternative splicing of protein translation genes in ELNAdv patients resulted in the induction of an integrated stress response and upregulation of inflammation-related genes. Finally, using machine learning techniques, we identified a splicing signature of four genes which refine the accuracy of existing risk prognosis schemes and validated it in a completely independent cohort. Conclusions: Our discoveries therefore identify aberrant alternative splicing as a molecular feature of adverse AML with clinical relevance.
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- 2020
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29. Performances of Targeted RNA Sequencing for the Analysis of Fusion Transcripts, Gene Mutation, and Expression in Hematological Malignancies
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Hayette, Sandrine, primary, Grange, Béatrice, additional, Vallee, Maxime, additional, Bardel, Claire, additional, Huet, Sarah, additional, Mosnier, Isabelle, additional, Chabane, Kaddour, additional, Simonet, Thomas, additional, Balsat, Marie, additional, Heiblig, Maël, additional, Tigaud, Isabelle, additional, Nicolini, Franck E., additional, Mareschal, Sylvain, additional, Salles, Gilles, additional, and Sujobert, Pierre, additional
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- 2021
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30. Performances of targeted RNA-sequencing for the analysis of fusion transcripts, gene mutation and expression in haematological malignancies
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Hayette, Sandrine, primary, Grange, Béatrice, additional, Vallee, Maxime, additional, Bardel, Claire, additional, Huet, Sarah, additional, Mosnier, Isabelle, additional, Chabane, Kaddour, additional, Simonet, Thomas, additional, Balsat, Marie, additional, Heiblig, Maël, additional, Tigaud, Isabelle, additional, Nicolini, Franck E., additional, Mareschal, Sylvain, additional, Salles, Gilles, additional, and Sujobert, Pierre, additional
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- 2020
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31. RNA Splicing Alterations Induce a Cellular Stress Response Associated with Poor Prognosis in Acute Myeloid Leukemia
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Anande, Govardhan, primary, Deshpande, Nandan P., additional, Mareschal, Sylvain, additional, Batcha, Aarif M.N., additional, Hampton, Henry R., additional, Herold, Tobias, additional, Lehmann, Soren, additional, Wilkins, Marc R., additional, Wong, Jason W.H., additional, Unnikrishnan, Ashwin, additional, and Pimanda, John E., additional
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- 2020
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32. RNA splicing alterations induce a cellular stress response associated with poor prognosis in AML
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Anande, Govardhan, primary, Deshpande, Nandan P., additional, Mareschal, Sylvain, additional, Batcha, Aarif M. N., additional, Hampton, Henry R., additional, Herold, Tobias, additional, Lehmann, Soren, additional, Wilkins, Marc R., additional, Wong, Jason W.H., additional, Unnikrishnan, Ashwin, additional, and Pimanda, John E., additional
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- 2020
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33. Identification of Recurrent Alternative RNA Splicing in Adverse-Risk Acute Myeloid Leukemia
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Anande, Govardhan, primary, Unnikrishnan, Ashwin, primary, Deshpande, Nandan, primary, Mareschal, Sylvain, primary, Batcha, Aarif M. N., primary, Herold, Tobias, primary, Lehmann, Sören, primary, Wilkins, Marc, primary, Wong, Jason, primary, and Pimanda, John, primary
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- 2019
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34. Refining diffuse large B-cell lymphoma subgroups using integrated analysis of molecular profiles
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Dubois, Sydney, primary, Tesson, Bruno, additional, Mareschal, Sylvain, additional, Viailly, Pierre-Julien, additional, Bohers, Elodie, additional, Ruminy, Philippe, additional, Etancelin, Pascaline, additional, Peyrouze, Pauline, additional, Copie-Bergman, Christiane, additional, Fabiani, Bettina, additional, Petrella, Tony, additional, Jais, Jean-Philippe, additional, Haioun, Corinne, additional, Salles, Gilles, additional, Molina, Thierry Jo, additional, Leroy, Karen, additional, Tilly, Hervé, additional, and Jardin, Fabrice, additional
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- 2019
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35. Prévalence, cinétique et valeur pronostique de la mutation XPO1 E571K dans le lymphome de Hodgkin
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Camus, Vincent, Stamatoullas, Aspasia, Mareschal, Sylvain, Viailly, Pierre-Julien, Sarafan-Vasseur, Nasrin, Bohers, Elodie, Dubois, Sydney, Picquenot, Jean-Michel, Ruminy, Philippe, Maingonnat, Catherine, Cornic, Marie, Tallon-Simon, Valérie, Becker, Stéphanie, Veresezan, Elena-Liana, Frebourg, Thierry, Vera, Pierre, Bastard, Christian, Tilly, Hervé, Jardin, Fabrice, Génomique et Médecine Personnalisée du Cancer et des Maladies Neuropsychiatriques (GPMCND), Université de Rouen Normandie (UNIROUEN), Normandie Université (NU)-Normandie Université (NU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre de Lutte Contre le Cancer Henri Becquerel Normandie Rouen (CLCC Henri Becquerel), service d'anatomo-pathologie, Service de médecine nucléaire [Rouen], CRLCC Haute Normandie-Centre de Lutte Contre le Cancer Henri Becquerel Normandie Rouen (CLCC Henri Becquerel), Equipe Quantification en Imagerie Fonctionnelle (QuantIF-LITIS), Laboratoire d'Informatique, de Traitement de l'Information et des Systèmes (LITIS), Institut national des sciences appliquées Rouen Normandie (INSA Rouen Normandie), Institut National des Sciences Appliquées (INSA)-Normandie Université (NU)-Institut National des Sciences Appliquées (INSA)-Normandie Université (NU)-Université de Rouen Normandie (UNIROUEN), Normandie Université (NU)-Université Le Havre Normandie (ULH), Normandie Université (NU)-Institut national des sciences appliquées Rouen Normandie (INSA Rouen Normandie), and Normandie Université (NU)
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[SDV.CAN]Life Sciences [q-bio]/Cancer ,ComputingMilieux_MISCELLANEOUS - Abstract
International audience
- Published
- 2017
36. Authors’ Reply
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Bobée, Victor, primary, Ruminy, Philippe, additional, Marchand, Vinciane, additional, Viailly, Pierre-Julien, additional, Abdel Sater, Ahmad, additional, Veresezan, Liana, additional, Drieux, Fanny, additional, Bérard, Caroline, additional, Bohers, Elodie, additional, Mareschal, Sylvain, additional, Dubois, Sydney, additional, Jais, Jean-Philippe, additional, Leroy, Karen, additional, Figeac, Martin, additional, Picquenot, Jean-Michel, additional, Molina, Thierry J., additional, Salles, Gilles, additional, Haioun, Corinne, additional, Tilly, Hervé, additional, and Jardin, Fabrice, additional
- Published
- 2018
- Full Text
- View/download PDF
37. Next-Generation Sequencing in Diffuse Large B-Cell Lymphoma Highlights Molecular Divergence and Therapeutic Opportunities: a LYSA Study
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Dubois , Sydney, Viailly , J., Mareschal , Sylvain, Bohers , Elodie, Bertrand , P., Ruminy , Philippe, Maingonnat , Catherine, Jais , Jean-Philippe, Peyrouze , Pauline, Figeac , Martin, Molina , Thierry, Desmots , Fabienne, Fest , Thierry, Haioun , Corinne, Lamy , Thierry, Copie-Bergman , Christiane, Briere , J., Petrella , Tony, Canioni , Danielle, Fabiani , Bettina, Coiffier , Bertrand, Delarue , Richard, Peyrade , Frédéric, Bosly , A., Andre , M., Ketterer , Nicolas, Salles , Gilles, Tilly , Hervé, Leroy , Karen, Jardin , Fabrice, Viailly , Pierre-Julien, Bertrand , Bertrand, Brière , Josette, André , André, André , Marc, Groupe d'étude des proliférations lymphoïdes (GPL), Université de Rouen Normandie (UNIROUEN), Normandie Université (NU)-Normandie Université (NU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Laboratoire d'Informatique, de Traitement de l'Information et des Systèmes (LITIS), Université Le Havre Normandie (ULH), Normandie Université (NU)-Normandie Université (NU)-Université de Rouen Normandie (UNIROUEN), Normandie Université (NU)-Institut national des sciences appliquées Rouen Normandie (INSA Rouen Normandie), Institut National des Sciences Appliquées (INSA)-Normandie Université (NU)-Institut National des Sciences Appliquées (INSA), Service d'informatique médicale et biostatistiques [CHU Necker], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Necker - Enfants Malades [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Centre de recherche des Cordeliers - Equipe 20 'ingénierie des connaissances en santé', Centre de Recherche des Cordeliers (CRC (UMR_S 872)), Université Pierre et Marie Curie - Paris 6 (UPMC)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Faculté de Médecine Henri Warembourg - Université de Lille, Plateforme de génomique fonctionnelle et structurelle [Lille], Institut pour la recherche sur le cancer de Lille [Lille] (IRCL)-Université de Lille, Droit et Santé, Service d'anatomie pathologique [CHU Necker], Microenvironnement et cancer (MiCa), Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), CHU Pontchaillou [Rennes], Service d'hématologie clinique, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Henri Mondor-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), INSERM U955, équipe 9, Département de pathologie [Mondor], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Henri Mondor-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Henri Mondor-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12)-Institut Mondor de Recherche Biomédicale (IMRB), Institut National de la Santé et de la Recherche Médicale (INSERM)-IFR10-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12)-Institut National de la Santé et de la Recherche Médicale (INSERM)-IFR10-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Gvh et Gvl : Physiopathologie Chez l'Homme et Chez l'Animal, Incidence et Role Therapeutique, Université Paris Diderot - Paris 7 (UPD7)-Institut National de la Santé et de la Recherche Médicale (INSERM), Service d'anatomo-pathologie [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Diderot - Paris 7 (UPD7)-Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], Hôpital Maisonneuve-Rosemont, Centre de référence des mastocytoses (CEREMAST), CHU Necker - Enfants Malades [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Service d'anatomie et cytologie pathologiques [CHU Saint-Antoine], Université Pierre et Marie Curie - Paris 6 (UPMC)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU), Service d'Hematologie, Hospices Civils de Lyon (HCL)-Centre Hospitalier Lyon Sud [CHU - HCL] (CHLS), Hospices Civils de Lyon (HCL), Laboratoire de Biologie Moléculaire de la Cellule (LBMC), École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Service d'immuno-hématologie pédiatrique [CHU Necker], Centre de Lutte contre le Cancer Antoine Lacassagne [Nice] (UNICANCER/CAL), UNICANCER-Université Côte d'Azur (UCA), CHU Dinant-Godinne UCL Namur, Department of Oncology, Lausanne Hospital, Lausanne Hospital, Centre Hospitalier Lyon Sud [CHU - HCL] (CHLS), Service de Pathologie, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Henri Mondor, Institut Mondor de Recherche Biomédicale (IMRB), Institut National de la Santé et de la Recherche Médicale (INSERM)-IFR10-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Institut National du Cancer (INCA), Université de Rennes (UR)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), Jonchère, Laurent, Rouen Business School, Groupe d'étude des proliférations lymphoïdes ( GPL ), Université de Rouen Normandie ( UNIROUEN ), Normandie Université ( NU ) -Normandie Université ( NU ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ), Centre de Recherche des Cordeliers ( CRC ), Université Paris Diderot - Paris 7 ( UPD7 ) -École pratique des hautes études ( EPHE ) -Université Pierre et Marie Curie - Paris 6 ( UPMC ) -Université Paris Descartes - Paris 5 ( UPD5 ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ), Université Lille 2 - Faculté de Médecine, Institut pour la recherche sur le cancer de Lille [Lille] ( IRCL ) -Université de Lille, Droit et Santé, AP-HP - Hôpital Cochin Broca Hôtel Dieu [Paris], Microenvironment, Cell Differentiation, Immunology and Cancer ( MICMAC ), Université de Rennes 1 ( UR1 ), Université de Rennes ( UNIV-RENNES ) -Université de Rennes ( UNIV-RENNES ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), Assistance publique - Hôpitaux de Paris (AP-HP)-Hôpital Henri Mondor-Université Paris-Est Créteil Val-de-Marne - Paris 12 ( UPEC UP12 ), Groupe Henri Mondor-Albert Chenevier, Assistance publique - Hôpitaux de Paris (AP-HP)-Hôpital Henri Mondor-Hôpital Albert Chenevier, Maisonneuve-Rosemont Hospital Research Center, University of Montreal, Service de pathologie [CHU Necker], Assistance publique - Hôpitaux de Paris (AP-HP)-CHU Necker - Enfants Malades [AP-HP], Centre de Recherche en Cancérologie de Lyon ( CRCL ), Université Claude Bernard Lyon 1 ( UCBL ), Université de Lyon-Université de Lyon-Centre Léon Bérard [Lyon]-Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Centre National de la Recherche Scientifique ( CNRS ), Service d’Hématologie [Centre Hospitalier Lyon Sud - HCL], Centre Hospitalier Lyon Sud [CHU - HCL] ( CHLS ), Hospices Civils de Lyon ( HCL ) -Hospices Civils de Lyon ( HCL ), Centre Antoine Lacassagne, CRLCC Antoine Lacassagne, Service d'hématologie [Hôpital Edouard Herriot - HCL], Hôpital Edouard Herriot [CHU - HCL], Institut Mondor de Recherche Biomédicale ( IMRB ), Institut National de la Santé et de la Recherche Médicale ( INSERM ) -IFR10-Université Paris-Est Créteil Val-de-Marne - Paris 12 ( UPEC UP12 ), Laboratoire d'Informatique, de Traitement de l'Information et des Systèmes ( LITIS ), Université Le Havre Normandie ( ULH ), Normandie Université ( NU ) -Normandie Université ( NU ) -Université de Rouen Normandie ( UNIROUEN ), Normandie Université ( NU ) -Institut national des sciences appliquées Rouen Normandie ( INSA Rouen Normandie ), Normandie Université ( NU ), Unité de Taphonomie médico-légale ( UTML ), Université de Lille-Centre Hospitalier Régional Universitaire [Lille] ( CHRU Lille ), Centre de Recherche des Cordeliers ( CRC (UMR_S 872) ), Université Pierre et Marie Curie - Paris 6 ( UPMC ) -Université Paris Descartes - Paris 5 ( UPD5 ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Centre National de la Recherche Scientifique ( CNRS ) -Université Pierre et Marie Curie - Paris 6 ( UPMC ) -Université Paris Descartes - Paris 5 ( UPD5 ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Centre National de la Recherche Scientifique ( CNRS ), Microenvironnement et cancer ( MiCa ), Assistance publique - Hôpitaux de Paris (AP-HP)-Hôpital Henri Mondor-Université Paris-Est Créteil Val-de-Marne - Paris 12 ( UPEC UP12 ) -Assistance publique - Hôpitaux de Paris (AP-HP)-Hôpital Henri Mondor-Université Paris-Est Créteil Val-de-Marne - Paris 12 ( UPEC UP12 ) -Institut Mondor de Recherche Biomédicale ( IMRB ), Institut National de la Santé et de la Recherche Médicale ( INSERM ) -IFR10-Université Paris-Est Créteil Val-de-Marne - Paris 12 ( UPEC UP12 ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -IFR10, Université Paris Diderot - Paris 7 ( UPD7 ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ), Assistance publique - Hôpitaux de Paris (AP-HP)-Université Paris Diderot - Paris 7 ( UPD7 ) -Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], Centre de référence des mastocytoses, Service d'anatomie et cytologie pathologiques, Université Pierre et Marie Curie - Paris 6 ( UPMC ) -Assistance publique - Hôpitaux de Paris (AP-HP)-CHU Saint-Antoine [APHP], Hospices Civils de Lyon ( HCL ) -Centre Hospitalier Lyon Sud [CHU - HCL] ( CHLS ), Hospices Civils de Lyon ( HCL ), Laboratoire de Biologie Moléculaire de la Cellule ( LBMC ), École normale supérieure - Lyon ( ENS Lyon ) -Université Claude Bernard Lyon 1 ( UCBL ), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Centre National de la Recherche Scientifique ( CNRS ), Assistance publique - Hôpitaux de Paris (AP-HP)-Hôpital Henri Mondor, Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Rouen Normandie (UNIROUEN), Normandie Université (NU)-Normandie Université (NU), Institut national des sciences appliquées Rouen Normandie (INSA Rouen Normandie), Institut National des Sciences Appliquées (INSA)-Normandie Université (NU)-Institut National des Sciences Appliquées (INSA)-Normandie Université (NU)-Université de Rouen Normandie (UNIROUEN), Normandie Université (NU)-Université Le Havre Normandie (ULH), Normandie Université (NU), Université Paris Descartes - Paris 5 (UPD5)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Descartes - Paris 5 (UPD5)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Université Paris Diderot - Paris 7 (UPD7)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], Université Côte d'Azur (UCA)-UNICANCER, CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), École normale supérieure de Lyon (ENS de Lyon)-Université Claude Bernard Lyon 1 (UCBL), UCL - SSS/IREC/MIRO - Pôle d'imagerie moléculaire, radiothérapie et oncologie, UCL - (MGD) Service d'hématologie, Groupe d'étude des proliférations lymphoïdes, Université de Rouen - Institut National de la Santé et de la Recherche Médicale (INSERM), Centre de Recherche des Cordeliers (CRC), Université Pierre et Marie Curie - Paris 6 (UPMC) - École pratique des hautes études (EPHE) - Université Paris Diderot - Paris 7 (UPD7) - Université Paris Descartes - Paris 5 (UPD5) - Institut National de la Santé et de la Recherche Médicale (INSERM), Institut pour la recherche sur le cancer de Lille [Lille] (IRCL) - Université de Lille, Droit et Santé, Université de Rennes 1 (UR1) - Institut National de la Santé et de la Recherche Médicale (INSERM) - Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), Assistance publique - Hôpitaux de Paris (AP-HP) - Hôpital Henri Mondor - Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Assistance publique - Hôpitaux de Paris (AP-HP) - Hôpital Henri Mondor - Hôpital Albert Chenevier, Assistance publique - Hôpitaux de Paris (AP-HP) - Groupe Hospitalier Saint-Louis-Lariboisière- Fernand-Widal - Université Paris Diderot - Paris 7 (UPD7), Centre de pathologie, Assistance publique - Hôpitaux de Paris (AP-HP) - AP-HP Hôpital Necker - Enfants Malades [Paris], Université Pierre et Marie Curie - Paris 6 (UPMC) - Assistance publique - Hôpitaux de Paris (AP-HP) - CHU Saint-Antoine [APHP], Service de Radio-Oncologie [Lyon], Hospices Civils de Lyon - Centre Hospitalier Lyon Sud [Pierre Bénite], Service d'hématologie biologique, Assistance publique - Hôpitaux de Paris (AP-HP) - Université Paris Descartes - Paris 5 (UPD5) - AP-HP Hôpital Necker - Enfants Malades [Paris], Institut National de la Santé et de la Recherche Médicale (INSERM) - IFR10 - Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Université Le Havre Normandie (ULH) - Université de Rouen - Institut National des Sciences Appliquées - Rouen (INSA Rouen), and Institut National des Sciences Appliquées (INSA) - Institut National des Sciences Appliquées (INSA)
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0301 basic medicine ,[SDV.MHEP.HEM] Life Sciences [q-bio]/Human health and pathology/Hematology ,Cancer Research ,Receptors, Cytoplasmic and Nuclear ,Cell Cycle Proteins ,TUMOR-SUPPRESSOR GENE ,Genome ,[ SDV.CAN ] Life Sciences [q-bio]/Cancer ,Antibodies, Monoclonal, Murine-Derived ,0302 clinical medicine ,hemic and lymphatic diseases ,Antineoplastic Combined Chemotherapy Protocols ,PROGNOSTIC-SIGNIFICANCE ,[ SDV.MHEP.HEM ] Life Sciences [q-bio]/Human health and pathology/Hematology ,[ SDV.IMM ] Life Sciences [q-bio]/Immunology ,Molecular Targeted Therapy ,Prospective Studies ,Precision Medicine ,Exome sequencing ,Genetics ,Oncogene Proteins ,B-Lymphocytes ,High-Throughput Nucleotide Sequencing ,[SDV.MHEP.HEM]Life Sciences [q-bio]/Human health and pathology/Hematology ,3. Good health ,DNA-Binding Proteins ,GENOME ,Phosphotransferases (Alcohol Group Acceptor) ,Oncology ,Vincristine ,030220 oncology & carcinogenesis ,[SDV.IMM]Life Sciences [q-bio]/Immunology ,Rituximab ,Lymphoma, Large B-Cell, Diffuse ,medicine.drug ,EXPRESSION ,[SDV.IMM] Life Sciences [q-bio]/Immunology ,Antineoplastic Agents ,[SDV.CAN]Life Sciences [q-bio]/Cancer ,FREQUENT ,Biology ,Karyopherins ,DNA sequencing ,03 medical and health sciences ,[SDV.CAN] Life Sciences [q-bio]/Cancer ,TARGETS ,Exome Sequencing ,medicine ,Humans ,RITUXIMAB ,Cyclophosphamide ,Tumor Necrosis Factor alpha-Induced Protein 3 ,Gene Expression Profiling ,CLASSICAL HODGKIN LYMPHOMA ,SOMATIC MUTATIONS ,Precision medicine ,medicine.disease ,Lymphoma ,Gene expression profiling ,030104 developmental biology ,Doxorubicin ,GTP-Binding Protein alpha Subunits, Gq-G11 ,Prednisone ,BURKITT-LYMPHOMA ,Diffuse large B-cell lymphoma - Abstract
Purpose: Next-generation sequencing (NGS) has detailed the genomic characterization of diffuse large B-cell lymphoma (DLBCL) by identifying recurrent somatic mutations. We set out to design a clinically feasible NGS panel focusing on genes whose mutations hold potential therapeutic impact. Furthermore, for the first time, we evaluated the prognostic value of these mutations in prospective clinical trials. Experimental Design: A Lymphopanel was designed to identify mutations in 34 genes, selected according to literature and a whole exome sequencing study of relapsed/refractory DLBCL patients. The tumor DNA of 215 patients with CD20+de novo DLBCL in the prospective, multicenter, and randomized LNH-03B LYSA clinical trials was sequenced to deep, uniform coverage with the Lymphopanel. Cell-of-origin molecular classification was obtained through gene expression profiling with HGU133+2.0 Affymetrix GeneChip arrays. Results: The Lymphopanel was informative for 96% of patients. A clear depiction of DLBCL subtype molecular heterogeneity was uncovered with the Lymphopanel, confirming that activated B-cell–like (ABC), germinal center B-cell like (GCB), and primary mediastinal B-cell lymphoma (PMBL) are frequently affected by mutations in NF-κB, epigenetic, and JAK–STAT pathways, respectively. Novel truncating immunity pathway, ITPKB, MFHAS1, and XPO1 mutations were identified as highly enriched in PMBL. Notably, TNFAIP3 and GNA13 mutations in ABC patients treated with R-CHOP were associated with significantly less favorable prognoses. Conclusions: This study demonstrates the contribution of NGS with a consensus gene panel to personalized therapy in DLBCL, highlighting the molecular heterogeneity of subtypes and identifying somatic mutations with therapeutic and prognostic impact. Clin Cancer Res; 22(12); 2919–28. ©2016 AACR. See related commentary by Lim and Elenitoba-Johnson, p. 2829
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- 2016
38. Recurrent mutations of the exportin 1 gene (XPO1) and their impact on selective inhibitor of nuclear export compounds sensitivity in primary mediastinal B-cell lymphoma
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Jardin, Fabrice, Pujals, Anais, Pelletier, Laura, Bohers, Elodie, Camus, Vincent, Mareschal, Sylvain, Dubois, Sydney, Sola, Brigitte, Ochmann, Marlène, Lemonnier, François, Viailly, Pierre-Julien, Bertrand, Philippe, Maingonnat, Catherine, Traverse-Glehen, Alexandra, Gaulard, Philippe, Damotte, Diane, Delarue, Richard, Haioun, Corinne, Argueta, Christian, Landesman, Yosef, Salles, Gilles, Jais, Jean-Philippe, Figeac, Martin, Copie-Bergman, Christiane, Molina, Thierry Jo, Picquenot, Jean Michel, Cornic, Marie, Fest, Thierry, Milpied, Noel, Lemasle, Emilie, Stamatoullas, Aspasia, Moeller, Peter, Dyer, Martin J S, Sundström, Christer, Bastard, Christian, Tilly, Hervé, Leroy, Karen, Groupe d'étude des proliférations lymphoïdes ( GPL ), Université de Rouen Normandie ( UNIROUEN ), Normandie Université ( NU ) -Normandie Université ( NU ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ), Service d'hématologie clinique, Assistance publique - Hôpitaux de Paris (AP-HP)-Hôpital Henri Mondor-Université Paris-Est Créteil Val-de-Marne - Paris 12 ( UPEC UP12 ), Microenvironnement cellulaire et pathologie ( MILPAT ), Université de Caen Normandie ( UNICAEN ), Normandie Université ( NU ) -Normandie Université ( NU ), Microenvironnement et cancer ( MiCa ), Université de Rennes 1 ( UR1 ), Université de Rennes ( UNIV-RENNES ) -Université de Rennes ( UNIV-RENNES ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), Centre de Recherche des Cordeliers ( CRC (UMR_S 872) ), Université Pierre et Marie Curie - Paris 6 ( UPMC ) -Université Paris Descartes - Paris 5 ( UPD5 ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Centre National de la Recherche Scientifique ( CNRS ), CHU Necker - Enfants Malades [AP-HP], Service d'hématologie [Hôpital Edouard Herriot - HCL], Hôpital Edouard Herriot [CHU - HCL], Hospices Civils de Lyon ( HCL ) -Hospices Civils de Lyon ( HCL ), Institut pour la recherche sur le cancer de Lille [Lille] ( IRCL ), Institut Mondor de Recherche Biomédicale ( IMRB ), Institut National de la Santé et de la Recherche Médicale ( INSERM ) -IFR10-Université Paris-Est Créteil Val-de-Marne - Paris 12 ( UPEC UP12 ), Université Paris Descartes - Paris 5 ( UPD5 ), Centre hospitalier universitaire de Nantes ( CHU Nantes ), Institute of Human Genetics, University of Ulm, Albert-Einstein-Allee 11, Ulm, Germany, University of Leicester, Department of Immunology, Genetics and Pathology, Science for Life Laboratory, Uppsala University, Uppsala, Sweden, Service hématologie Poitiers, Centre hospitalier universitaire de Poitiers ( CHU Poitiers ), The authors thank Dr. Lin Chook for her critical review and for providing the molecular data on the conformation of XPO1/CRM1 protein residues., Groupe d'étude des proliférations lymphoïdes (GPL), Université de Rouen Normandie (UNIROUEN), Normandie Université (NU)-Normandie Université (NU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Henri Mondor-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Microenvironnement cellulaire et pathologie (MILPAT), Université de Caen Normandie (UNICAEN), Normandie Université (NU)-Normandie Université (NU), Microenvironnement et cancer (MiCa), Université de Rennes (UR)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), Centre de Recherche des Cordeliers (CRC (UMR_S 872)), Université Pierre et Marie Curie - Paris 6 (UPMC)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Hospices Civils de Lyon (HCL)-Hospices Civils de Lyon (HCL), Institut pour la recherche sur le cancer de Lille [Lille] (IRCL), Institut Mondor de Recherche Biomédicale (IMRB), Institut National de la Santé et de la Recherche Médicale (INSERM)-IFR10-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Université Paris Descartes - Paris 5 (UPD5), Centre hospitalier universitaire de Nantes (CHU Nantes), Universität Ulm - Ulm University [Ulm, Allemagne], Uppsala University, Centre hospitalier universitaire de Poitiers (CHU Poitiers), Chard-Hutchinson, Xavier, Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), Université Paris Descartes - Paris 5 (UPD5)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), and Institute of Human Genetics, University of Ulm
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[SDV.MHEP.HEM] Life Sciences [q-bio]/Human health and pathology/Hematology ,Adult ,Male ,Lymphoma, B-Cell ,Adolescent ,Active Transport, Cell Nucleus ,Receptors, Cytoplasmic and Nuclear ,[SDV.CAN]Life Sciences [q-bio]/Cancer ,Karyopherins ,Mediastinal Neoplasms ,[ SDV.CAN ] Life Sciences [q-bio]/Cancer ,Young Adult ,[SDV.CAN] Life Sciences [q-bio]/Cancer ,Cell Line, Tumor ,[ SDV.MHEP.HEM ] Life Sciences [q-bio]/Human health and pathology/Hematology ,Humans ,Aged ,Clinical Laboratory Medicine ,Gene Expression Profiling ,[SDV.MHEP.HEM]Life Sciences [q-bio]/Human health and pathology/Hematology ,Sequence Analysis, DNA ,Middle Aged ,Triazoles ,Hodgkin Disease ,Klinisk laboratoriemedicin ,Hydrazines ,Acrylates ,Mutation ,Female ,Biomarkers - Abstract
Primary mediastinal B-cell lymphoma (PMBL) is an entity of B-cell lymphoma distinct from the other molecular subtypes of diffuse large B-cell lymphoma (DLBCL). We investigated the prevalence, specificity, and clinical relevance of mutations of XPO1, which encodes a member of the karyopherin-β nuclear transporters, in a large cohort of PMBL. PMBL cases defined histologically or by gene expression profiling (GEP) were sequenced and the XPO1 mutational status was correlated to genetic and clinical characteristics. The XPO1 mutational status was also assessed in DLBCL, Hodgkin lymphoma (HL) and mediastinal gray-zone lymphoma (MGZL).The biological impact of the mutation on Selective Inhibitor of Nuclear Export (SINE) compounds (KPT-185/330) sensitivity was investigated in vitro. XPO1 mutations were present in 28/117 (24%) PMBL cases and in 5/19 (26%) HL cases but absent/rare in MGZL (0/20) or DLBCL (3/197). A higher prevalence (50%) of the recurrent codon 571 variant (p.E571K) was observed in GEP-defined PMBL and was associated with shorter PFS. Age, International Prognostic Index and bulky mass were similar in XPO1 mutant and wild-type cases. KPT-185 induced a dose-dependent decrease in cell proliferation and increased cell-death in PMBL cell lines harboring wild type or XPO1 E571K mutant alleles. Experiments in transfected U2OS cells further confirmed that the XPO1 E571K mutation does not have a drastic impact on KPT-330 binding. To conclude the XPO1 E571K mutation represents a genetic hallmark of the PMBL subtype and serves as a new relevant PMBL biomarker. SINE compounds appear active for both mutated and wild-type protein. Am. J. Hematol. 91:923-930, 2016. © 2016 Wiley Periodicals, Inc.
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- 2016
39. Determination of Molecular Subtypes of Diffuse Large B-Cell Lymphoma Using a Reverse Transcriptase Multiplex Ligation-Dependent Probe Amplification Classifier
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Bobée, Victor, primary, Ruminy, Philippe, additional, Marchand, Vinciane, additional, Viailly, Pierre-Julien, additional, Abdel Sater, Ahmad, additional, Veresezan, Liana, additional, Drieux, Fanny, additional, Bérard, Caroline, additional, Bohers, Elodie, additional, Mareschal, Sylvain, additional, Dubois, Sydney, additional, Jais, Jean-Philippe, additional, Leroy, Karen, additional, Figeac, Martin, additional, Picquenot, Jean-Michel, additional, Molina, Thierry Jo, additional, Salles, Gilles, additional, Haioun, Corinne, additional, Tilly, Hervé, additional, and Jardin, Fabrice, additional
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- 2017
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40. Non-invasive detection of somatic mutations using next-generation sequencing in primary central nervous system lymphoma
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Fontanilles, Maxime, primary, Marguet, Florent, additional, Bohers, Élodie, additional, Viailly, Pierre-Julien, additional, Dubois, Sydney, additional, Bertrand, Philippe, additional, Camus, Vincent, additional, Mareschal, Sylvain, additional, Ruminy, Philippe, additional, Maingonnat, Catherine, additional, Lepretre, Stéphane, additional, Veresezan, Elena-Liana, additional, Derrey, Stéphane, additional, Tilly, Hervé, additional, Picquenot, Jean-Michel, additional, Laquerrière, Annie, additional, and Jardin, Fabrice, additional
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- 2017
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41. Application of the cghRA framework to the genomic characterization of Diffuse Large B-Cell Lymphoma
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Mareschal, Sylvain, primary, Ruminy, Philippe, additional, Alcantara, Marion, additional, Villenet, Céline, additional, Figeac, Martin, additional, Dubois, Sydney, additional, Bertrand, Philippe, additional, Bouzelfen, Abdelilah, additional, Viailly, Pierre-Julien, additional, Penther, Dominique, additional, Tilly, Hervé, additional, Bastard, Christian, additional, and Jardin, Fabrice, additional
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- 2017
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42. Biological and Clinical Relevance of Associated Genomic Alterations in MYD88 L265P and non-L265P–Mutated Diffuse Large B-Cell Lymphoma: Analysis of 361 Cases
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Dubois, Sydney, primary, Viailly, Pierre-Julien, additional, Bohers, Elodie, additional, Bertrand, Philippe, additional, Ruminy, Philippe, additional, Marchand, Vinciane, additional, Maingonnat, Catherine, additional, Mareschal, Sylvain, additional, Picquenot, Jean-Michel, additional, Penther, Dominique, additional, Jais, Jean-Philippe, additional, Tesson, Bruno, additional, Peyrouze, Pauline, additional, Figeac, Martin, additional, Desmots, Fabienne, additional, Fest, Thierry, additional, Haioun, Corinne, additional, Lamy, Thierry, additional, Copie-Bergman, Christiane, additional, Fabiani, Bettina, additional, Delarue, Richard, additional, Peyrade, Frédéric, additional, André, Marc, additional, Ketterer, Nicolas, additional, Leroy, Karen, additional, Salles, Gilles, additional, Molina, Thierry J., additional, Tilly, Hervé, additional, and Jardin, Fabrice, additional
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- 2017
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43. Oncogenic events rather than antigen selection pressure may be the main driving forces for relapse in diffuse large B‐cell lymphomas
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Rizzo, David, primary, Viailly, Pierre‐Julien, additional, Mareschal, Sylvain, additional, Bohers, Elodie, additional, Picquenot, Jean‐Michel, additional, Penther, Dominique, additional, Dubois, Sydney, additional, Marchand, Vinciane, additional, Bertrand, Philippe, additional, Maingonnat, Catherine, additional, Etancelin, Pascaline, additional, Feuillard, Jean, additional, Bastard, Christian, additional, Tilly, Hervé, additional, Jardin, Fabrice, additional, and Ruminy, Philippe, additional
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- 2016
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44. Biological and Clinical Relevance of Associated Genomic Alterations in MYD88 L265P and Non-L265P Mutated Diffuse Large B-Cell Lymphoma: Analysis of 361 Cases
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Dubois, Sydney, primary, Viailly, Pierre-Julien, additional, Bohers, Elodie, additional, Bertrand, Philippe, additional, Ruminy, Philippe, additional, Marchand, Vinciane, additional, Maingonnat, Catherine, additional, Mareschal, Sylvain, additional, Picquenot, Jean-Michel, additional, Penther, Dominique, additional, Jais, Jean-Philippe, additional, Tesson, Bruno, additional, Peyrouze, Pauline, additional, Figeac, Martin, additional, Desmots, Fabienne, additional, Fest, Thierry, additional, Haioun, Corinne, additional, Lamy, Thierry, additional, Copie-Bergman, Christiane, additional, Fabiani, Bettina, additional, Delarue, Richard, additional, Peyrade, Frédéric, additional, Andre, Marc, additional, Ketterer, Nicolas, additional, Leroy, Karen, additional, Salles, Gilles A., additional, Molina, Thierry Jo, additional, Tilly, Hervé, additional, and Jardin, Fabrice, additional
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- 2016
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45. Integrated Analysis of IGHV Gene Status, Cell-of-Origin Signature and Genomic Features in Diffuse Large B-Cell Lymphoma
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Etancelin, Pascaline, primary, Dubois, Sydney, additional, Viailly, Pierre-Julien, additional, Bohers, Elodie, additional, Bertrand, Philippe, additional, Ruminy, Philippe, additional, Maingonnat, Catherine, additional, Picquenot, Jean-Michel, additional, Mareschal, Sylvain, additional, Jais, Jean-Philippe, additional, Tesson, Bruno, additional, Peyrouze, Pauline, additional, Figeac, Martin, additional, Fest, Thierry, additional, Haioun, Corinne, additional, Lamy, Thierry, additional, Copie-Bergman, Christiane, additional, Fabiani, Bettina, additional, Delarue, Richard, additional, Peyrade, Frédéric, additional, Marc, André, additional, Ketterer, Nicolas, additional, Leroy, Karen, additional, Salles, Gilles A., additional, Molina, Thierry Jo, additional, Tilly, Hervé, additional, Stevenson, Freda K, additional, and Jardin, Fabrice, additional
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- 2016
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46. GenerateReports: an Ion Torrent plugin summarizing a whole NGS experiment for clinical interpretation
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Viailly, Pierre Julien, Mareschal, Sylvain, Bertrand, Philippe, Dubois, Sydney, Bohers, Elodie, Maingonnat, Catherine, Lecroq, Thierry, Dauchel, Hélène, Tilly, Herve, Jardin, Fabrice, Groupe d'étude des proliférations lymphoïdes (GPL), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Rouen Normandie (UNIROUEN), Normandie Université (NU)-Normandie Université (NU), Génomique et Médecine Personnalisée du Cancer et des Maladies Neuropsychiatriques (GPMCND), Université de Rouen Normandie (UNIROUEN), Normandie Université (NU)-Normandie Université (NU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Institute for Research and Innovation in Biomedicine (IRIB), Normandie Université (NU)-Normandie Université (NU)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM), Equipe Traitement de l'information en Biologie Santé (TIBS - LITIS), Laboratoire d'Informatique, de Traitement de l'Information et des Systèmes (LITIS), Institut national des sciences appliquées Rouen Normandie (INSA Rouen Normandie), Institut National des Sciences Appliquées (INSA)-Normandie Université (NU)-Institut National des Sciences Appliquées (INSA)-Normandie Université (NU)-Université de Rouen Normandie (UNIROUEN), Normandie Université (NU)-Université Le Havre Normandie (ULH), Normandie Université (NU)-Institut national des sciences appliquées Rouen Normandie (INSA Rouen Normandie), Normandie Université (NU), Institut Mondor de Recherche Biomédicale (IMRB), Institut National de la Santé et de la Recherche Médicale (INSERM)-IFR10-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Bohers, Elodie, Université Le Havre Normandie (ULH), Normandie Université (NU)-Normandie Université (NU)-Université de Rouen Normandie (UNIROUEN), Institut National des Sciences Appliquées (INSA)-Normandie Université (NU)-Institut National des Sciences Appliquées (INSA)-Université Le Havre Normandie (ULH), Institut National des Sciences Appliquées (INSA)-Normandie Université (NU)-Institut National des Sciences Appliquées (INSA), and Lecroq, Thierry
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[SDV] Life Sciences [q-bio] ,[SDV]Life Sciences [q-bio] ,ComputingMethodologies_GENERAL ,[INFO.INFO-BI]Computer Science [cs]/Bioinformatics [q-bio.QM] ,ComputingMilieux_MISCELLANEOUS ,[INFO.INFO-BI] Computer Science [cs]/Bioinformatics [q-bio.QM] - Abstract
International audience; The increasing arrival of Next Generation Sequencing technologies in diagnostic laboratories creates a need to develop tools for rapid data interpretation. For example, targeted cancer sequencing allows biologists to focus on a selected range of known cancer-relevant genes and has become a choice strategy to quickly screen patients' mutational profiles. Although these profiles can aid in developing personalized therapy, their interpretation remains difficult. The aim is now to develop tools to provide a quick understanding of mutation profiles, highlighting the most impactful anomalies.Here, we present an open-source integrated IonTorrent plugin called GenerateReports. This tool aggregates data in a single clinical report, enabling the clear visualization of the main results for each sample sequenced. GenerateReports is based on CoverageAnalysis and VariantCaller Torrent Suite plugins results but goes even further by performing annotation of single nucleotide variants and searching for copy-number variations (CNVs). Thus, the biologist has access to sample identification, run and sample quality metrics, annotated and stratified variants, CNVs detected with statistical relevance and information about experimental and informatics traceability, all in a single PDF report for each sample sequenced. An associated interfaced database allows for further statistical studies. It could help to identify sequencing artifacts by Sanger validation storing and to stratify thousands of anomalies in several runs.We illustrate the results obtained using this plugin through the sequencing of a patient suffering from Diffuse Large B-Cell Lymphoma.
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- 2015
47. Whole Exome Sequencing of refractory aggressive B-cell lymphomas identified recurrent mutations of the exportin 1 gene (XPO1) in Primary Mediastinal B-cell Lymphoma subtype. A LYSA study
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Jardin, Fabrice, Pujals, Anaïs, Pelletier, Laura, Bohers, Elodie, Mareschal, Sylvain, Ochmann, Marlène, Lemonnier, Francois, Camus, Vincent, Bertrand, Philippe, Traverse-Glehen, Alexandra, Gaulard, Philippe, Damotte, Diane, Delarue, Richard, Haioun, Corinne, Landesman, Yosef, Salles, Gilles, Jais, Jean Philippe, Jo Molina, Thierry, Picquenot, Jean Michel, Fest, Thierry, Milpied, Noel, Lemasle, Emilie, Tilly, Herve, Leroy, Karen, Génomique et Médecine Personnalisée du Cancer et des Maladies Neuropsychiatriques (GPMCND), Université de Rouen Normandie (UNIROUEN), Normandie Université (NU)-Normandie Université (NU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Groupe d'étude des proliférations lymphoïdes (GPL), Institut Mondor de Recherche Biomédicale (IMRB), Institut National de la Santé et de la Recherche Médicale (INSERM)-IFR10-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Microenvironnement et cancer (MiCa), Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), Centre Hospitalier Lyon Sud [CHU - HCL] (CHLS), Hospices Civils de Lyon (HCL), Centre de Recherche des Cordeliers (CRC (UMR_S_1138 / U1138)), École pratique des hautes études (EPHE), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Université Paris Diderot - Paris 7 (UPD7)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), Service d'immuno-hématologie pédiatrique [CHU Necker], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Necker - Enfants Malades [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Service d'hématologie clinique, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Henri Mondor-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Karyopharm Therapeutics Inc., Newton, MA, U918, Service d'hématologie [Hôpital Edouard Herriot - HCL], Hôpital Edouard Herriot [CHU - HCL], Hospices Civils de Lyon (HCL)-Hospices Civils de Lyon (HCL), Service d'informatique médicale et biostatistiques [CHU Necker], CHU Necker - Enfants Malades [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Service d'Hématologie et Thérapie Cellulaire, CHU Bordeaux [Bordeaux]-Hôpital Haut-Lévêque [CHU Bordeaux], CHU Bordeaux [Bordeaux], Centre de Lutte Contre le Cancer Henri Becquerel Normandie Rouen (CLCC Henri Becquerel), Université de Rennes (UR)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), École Pratique des Hautes Études (EPHE), Bohers, Elodie, École pratique des hautes études (EPHE)-Université Paris Diderot - Paris 7 (UPD7)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-CHU Necker - Enfants Malades [AP-HP], and Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Hôpital Henri Mondor-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12)
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[SDV] Life Sciences [q-bio] ,[SDV]Life Sciences [q-bio] - Abstract
International audience; Introduction: Although diffuse large B‐cell lymphoma (DLBCL) has largely benefited from immunochemotherapy combinations in the past decade, 30% to 40% of patients still do not respond to treatment or relapse rapidly, underlying the need for understanding the mechanisms involved and identifying predictive biomarkers. To address this issue, we performed whole exome sequencing (WES) in a cohort of refractory/relapsed (RR) DLBCLs included in the LYSA clinical trial program. Methods: Fourteen normal/tumoural pairs of exomes from patients who progressed or relapsed within 12 months were sequenced on a HiSeq2000 platform. These cases had been classified as GCB (n = 4), ABC (n = 4), primary mediastinal B‐cell lymphoma (PMBL) (n = 4) subtypes or unclassified (n = 2), using Affymetrix U133 + 2 arrays. To refine the results obtained with WES, we performed high‐throughput targeted resequencing in 216 patients enroled in the LNH03 LYSA (LYmphoma Study Association) clinical trial programme and sequenced additional cohorts by Sanger method to assess the frequency and specificity of the candidate mutations. Results: WES identified several recurrent somatic mutations that are under investigation. Among candidate mutations, we identified a recurrent point mutation (p.E571K) targeting the Exportin 1 gene (XPO1) in 2/4 RR PMBL. XPO1 encodes a cargo protein mediating the nuclear export of multiple tumour suppressor proteins, including p53. Targeted resequencing was performed in four cohorts including GEP‐defined PMBLs (n = 36, cohort 1), PMBLs defined by histological criteria (n = 81, cohort 2), Hodgkin lymphoma (HL) cases and gray‐zone lymphomas (GZL) (22 HLs and 19 Reed–Sternberg micro‐dissected HLs, 20 GZLs, cohort 3) and DLBCL‐NOS (n = 194, 81 ABC, 81 GCB, 32 unclassified, cohort 4). XPO1 mutations were observed in 16/36 (44%) cases of PMBL cohort 1 and 10/81cases (12%) of cohort 2. By contrast, no mutation was observed in cohort 3, and only 3 cases (1.5%) were mutated in cohort 4. Copy number gains of XPO1 were observed in 8/22 PMBL cases (3 to 7 copies). In cohort 1, XPO1 mutation was significantly associated with a decreased PFS and OS [3y OS = 74% CI95% (55–100) as compared to 3y OS = 95% (86–100), log‐rank test p = 0.04]. The highly recurrent E571K variant (27/29 mutations) is located in the NES binding groove related to the cargo function. The effects of KPT‐185, a small inhibitor of nuclear export (SINE) that blocks XPO1‐dependent nuclear export, were assessed in 3 PMBL cell lines (MedB‐1, Karpas1106 and U2940) using cell proliferation and apoptosis assays. The XPO1 E571K mutated MedB‐1 cells showed a decreased response to the compound compared to the 2 other cell lines which are XPO1 wild type. Conclusions: XPO1 mutations represent a new distinctive genetic feature of the PMBL subtype and could be a biomarker with prognostic impact. The effect of the recurrent E571K variant on the cargo function of XPO1 is currently investigated.
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- 2015
48. Séquençage à haut débit dans les lymphomes diffus à grandes cellules : de la biopsie ganglionnaire à la biopsie « liquide » ?
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Bohers, Elodie, Viailly, Pierre Julien, Dubois, Sydney, Bertrand, Philippe, Maingonnat, Catherine, Mareschal, Sylvain, Ruminy, Philippe, Picquenot, Jean Michel, Bastard, Christian, Tilly, Herve, Jardin, Fabrice, Groupe d'étude des proliférations lymphoïdes (GPL), Université de Rouen Normandie (UNIROUEN), Normandie Université (NU)-Normandie Université (NU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Génomique et Médecine Personnalisée du Cancer et des Maladies Neuropsychiatriques (GPMCND), and Centre de Lutte Contre le Cancer Henri Becquerel Normandie Rouen (CLCC Henri Becquerel)
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[SDV]Life Sciences [q-bio] - Abstract
International audience; IntroductionLes techniques de Next generation sequencing (NGS) ont permis d’identifier des mutations récurrentes et fréquentes dans les lymphomes diffus à grandes cellules de phénotype B (LDGCB) touchant des gènes impliqués dans des voies biologiques fondamentales telles que la signalisation du BCR (CD79A/CD79B), la voie NF-B (CARD11), la voie des Toll-like récepteurs (MYD88), l’immunité (CD58, TNFSRF14, B2M), le cycle cellulaire (TP53, BCL2) ou la régulation épigénétique (EZH2,CREBBP, MLL2) . Dans les tumeurs solides, l’ADN libre circulant contenu dans le plasma (ADNp), libéré par les cellules tumorales apoptotiques ou nécrotiques est considéré comme un biomarqueur reflétant les caractéristiques génétiques de la tumeur primitive et, de ce fait, à l’origine du concept de « biopsie liquide ». La pertinence clinique et biologique de l’ADNp et la validité de ce concept dans les LDGCB ne sont en revanche pas connues.Matériels et méthodes12 cas de LDGCB (6 sous-types GCB, 5 ABC, 1 non classé, stade I = 3 ; stade III =5 ; stade IV = 4, aucune atteinte médullaire) non préalablement traités pour lesquels de l’ADN extrait d’une biopsie tumorale ganglionnaire (ADNg) et de l’ADN extrait de plasma étaient disponibles ont été inclus. Un lymphopanel permettant le séquençage de 34 gènes a été établi, certains gènes pouvant faire l’objet d’une thérapie ciblée. Après PCR multiplexe générant 872 amplicons, le séquençage de l’ADNg a été réalisé par PGM ® (Life technologies). Afin d’améliorer la sensibilité du séquençage de l’ADNp (10 ng), les variants nucléotidiques (SNV) identifiés dans la tumeur ont été recherchés en ciblant spécifiquement les amplicons d’intérêt. RésultatsDes profils mutationnels caractéristiques touchant les gènes MYD88, CD79A/B, PIM1, PRDM1, CARD11 et IRF4 ou les gènes EZH2, BCL2, GNA13 et TNFSRF14 ont été observés respectivement dans les LDGCB-ABC et les LDGCB-GCB. Le nombre moyen de reads (profondeur) ciblant les régions mutées était de 241 pour l’ADNg (range 23-741) et de 5987 (6-22 541) pour l’ADNp (soit une profondeur 24 fois supérieure). Dans 11/12 cas, le profil mutationnel observé dans l’ADNg était détectable dans l’ADNp. La fréquence allélique des variants (VAF) était en moyenne de 35% (17-64%) dans l’ADNg et de 11% dans l’ADNp correspondant (2-89%). Les LDGCB de faible masse tumorale (stade I, taux de LDH normaux) ont les VAF et les concentrations d’ADNp les plus faibles. En revanche, les LDGCB ayant les VAF les plus élevées dans l’ADNp sont de stade III / IV. De plus dans ces derniers cas, la distribution sous-clonale des SNV observée dans la tumeur est conservée dans l’ADNp.ConclusionNotre étude valide la faisabilité et la pertinence d’une analyse par NGS de l’ADNp, confirmant le concept de « biopsie liquide » dans les LDGCB. Une étude prospective est en cours pour confirmer ces résultats et utiliser le séquençage de l’ADNp pour le choix d’une thérapie ciblée ou le suivi de la maladie résiduelle.
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- 2015
49. Recurrent somatic mutations in diffuse large B cell lymphoma assessed by high throughput targeted sequencing highlight molecular subtypes’ genetic divergence: a LYSA study
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Dubois, Sydney, Viailly, Pierre Julien, Mareschal, Sylvain, Bertrand, Philippe, Bohers, Elodie, Maingonnat, Catherine, Jais, Jean Philippe, Figeac, Martin, Jo Molina, Thierry, Desmots-Loyer, Fabienne, Fest, Thierry, Salles, Gilles, Haioun, Corinne, Lamy, Thierry, Tilly, Herve, Leroy, Karen, Jardin, Fabrice, Bohers, Elodie, Groupe d'étude des proliférations lymphoïdes (GPL), Université de Rouen Normandie (UNIROUEN), Normandie Université (NU)-Normandie Université (NU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Génomique et Médecine Personnalisée du Cancer et des Maladies Neuropsychiatriques (GPMCND), Service d'informatique médicale et biostatistiques [CHU Necker], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Necker - Enfants Malades [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Plateforme de génomique fonctionnelle et structurelle [Lille], Institut pour la recherche sur le cancer de Lille [Lille] (IRCL)-Université de Lille, Droit et Santé, Département de Pathologie [CHU Necker], Université Paris Descartes - Paris 5 (UPD5)-Université Sorbonne Paris Cité (USPC)-CHU Necker - Enfants Malades [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Microenvironment, Cell Differentiation, Immunology and Cancer (MICMAC), Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), Microenvironnement et cancer (MiCa), Service d'hématologie [Hôpital Edouard Herriot - HCL], Hôpital Edouard Herriot [CHU - HCL], Hospices Civils de Lyon (HCL)-Hospices Civils de Lyon (HCL), Laboratoire de biologie et modélisation de la cellule (LBMC UMR 5239), École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Service d'hématologie clinique, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Henri Mondor-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Institut Mondor de Recherche Biomédicale (IMRB), Institut National de la Santé et de la Recherche Médicale (INSERM)-IFR10-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Université de Rennes (UR)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), École normale supérieure de Lyon (ENS de Lyon)-Université Claude Bernard Lyon 1 (UCBL), Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-CHU Necker - Enfants Malades [AP-HP], and Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Hôpital Henri Mondor-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12)
- Subjects
[SDV] Life Sciences [q-bio] ,[SDV]Life Sciences [q-bio] - Abstract
International audience; Introduction: Gene expression profiling (GEP) has identified three main subtypes of diffuse large B cell lymphoma (DLBCL): germinal centre B‐cell like (GCB), activated B‐cell like (ABC) and primary mediastinal B‐cell lymphoma (PMBL). Although next generation sequencing (NGS) has enabled a more detailed genomic characterization of DLBCL, the mutation patterns observed in different studies have been heterogeneous, highlighting the need for a consensus gene panel. Furthermore, the prognostic value of these mutations has yet to be evaluated in prospective clinical trials. Methods: A Lymphopanel designed to identify mutations in 34 genes important for lymphomagenesis was used to sequence tumour DNA of 216 patients with de novo DLBCL in prospective, multicentric and randomized LNH‐03B clinical trials led by the Groupe d'Etude du Lymphome Adulte (GELA), using the Ion PGM™ system. GEP identified 81 GCB, 81 ABC, 32 unclassified and 22 PMBL samples. Results: The Lymphopanel was informative for 96% of patients: 13975 variants were identified with a median sequencing depth of 225x, and 1075 (7.7%) were validated after filtering for variant quality, SNPs and functional relevance. The mean mutation rate per megabase was 56.7, and PMBL subtype was significantly more mutated than the other subtypes (p = 7.4 × 10e−5). We confirmed that the ABC subtype is dominated by NFkB pathway mutations (46% of variants), the GCB subtype is dominated by epigenetic pathway mutations (34% of variants) and the PMBL subtype is frequently mutated in JAK‐STAT and immunity pathways (respectively 27% and 22% of variants). The Lymphopanel confirmed subtype‐enriched mutations such as MYD88, PIM1, CD79B and IRF4 variants among ABC, BCL2, CREBBP, EZH2, MEF2B and TNFRSF14 variants among GCB and SOCS1, STAT6 and TNFAIP3 variants among PMBL. The immunity pathway seems to play a crucial role in PMBL, with respectively 59%, 36% and 45% of patients presenting mutations in B2M, CD58 and CIITA. These mutations mostly lead to truncated proteins, suggesting a predilection for immune system escape in PMBL. ITPKB, MFHAS1 and XPO1 mutations, whose roles in lymphomagenesis are unclear, were heavily weighted toward PMBL and presented mutations in respectively 40.9%, 27.3% and 31.8% of PMBL patients. XPO1 mutations especially were almost exclusively PMBL specific. Furthermore, clinical correlations were found for certain gene mutations among the total cohort, notably with age (B2M, CD79B, CIITA, KMT2D, MYD88, SOCS1, STAT6, ITPKB and XPO1), Ann Arbor stage (B2M) and IPI (B2M and STAT6). TNFAIP3 mutations in ABC patients were associated with a less favourable OS (FDR
- Published
- 2015
50. Molecular Profile and FDG-PET/CT Total Metabolic Tumor Volume Improve Risk Classification at Diagnosis for Patients with Diffuse Large B-Cell Lymphoma
- Author
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Cottereau, Anne-Ségolène, primary, Lanic, Hélène, additional, Mareschal, Sylvain, additional, Meignan, Michel, additional, Vera, Pierre, additional, Tilly, Hervé, additional, Jardin, Fabrice, additional, and Becker, Stéphanie, additional
- Published
- 2016
- Full Text
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