35 results on '"Guerrini-Rousseau, Lea"'
Search Results
2. Constitutional Microsatellite Instability, Genotype, and Phenotype Correlations in Constitutional Mismatch Repair Deficiency
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Gallon, Richard, Phelps, Rachel, Hayes, Christine, Brugieres, Laurence, Guerrini-Rousseau, Léa, Colas, Chrystelle, Muleris, Martine, Ryan, Neil A.J., Evans, D. Gareth, Grice, Hannah, Jessop, Emily, Kunzemann-Martinez, Annabel, Marshall, Lilla, Schamschula, Esther, Oberhuber, Klaus, Azizi, Amedeo A., Baris Feldman, Hagit, Beilken, Andreas, Brauer, Nina, Brozou, Triantafyllia, Dahan, Karin, Demirsoy, Ugur, Florkin, Benoît, Foulkes, William, Januszkiewicz-Lewandowska, Danuta, Jones, Kristi J., Kratz, Christian P., Lobitz, Stephan, Meade, Julia, Nathrath, Michaela, Pander, Hans-Jürgen, Perne, Claudia, Ragab, Iman, Ripperger, Tim, Rosenbaum, Thorsten, Rueda, Daniel, Sarosiek, Tomasz, Sehested, Astrid, Spier, Isabel, Suerink, Manon, Zimmermann, Stefanie-Yvonne, Zschocke, Johannes, Borthwick, Gillian M., Wimmer, Katharina, Burn, John, Jackson, Michael S., and Santibanez-Koref, Mauro
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- 2023
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3. Spectrum and prevalence of genetic predisposition in medulloblastoma: a retrospective genetic study and prospective validation in a clinical trial cohort.
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Waszak, Sebastian M, Northcott, Paul A, Buchhalter, Ivo, Robinson, Giles W, Sutter, Christian, Groebner, Susanne, Grund, Kerstin B, Brugières, Laurence, Jones, David TW, Pajtler, Kristian W, Morrissy, A Sorana, Kool, Marcel, Sturm, Dominik, Chavez, Lukas, Ernst, Aurelie, Brabetz, Sebastian, Hain, Michael, Zichner, Thomas, Segura-Wang, Maia, Weischenfeldt, Joachim, Rausch, Tobias, Mardin, Balca R, Zhou, Xin, Baciu, Cristina, Lawerenz, Christian, Chan, Jennifer A, Varlet, Pascale, Guerrini-Rousseau, Lea, Fults, Daniel W, Grajkowska, Wiesława, Hauser, Peter, Jabado, Nada, Ra, Young-Shin, Zitterbart, Karel, Shringarpure, Suyash S, De La Vega, Francisco M, Bustamante, Carlos D, Ng, Ho-Keung, Perry, Arie, MacDonald, Tobey J, Hernáiz Driever, Pablo, Bendel, Anne E, Bowers, Daniel C, McCowage, Geoffrey, Chintagumpala, Murali M, Cohn, Richard, Hassall, Timothy, Fleischhack, Gudrun, Eggen, Tone, Wesenberg, Finn, Feychting, Maria, Lannering, Birgitta, Schüz, Joachim, Johansen, Christoffer, Andersen, Tina V, Röösli, Martin, Kuehni, Claudia E, Grotzer, Michael, Kjaerheim, Kristina, Monoranu, Camelia M, Archer, Tenley C, Duke, Elizabeth, Pomeroy, Scott L, Shelagh, Redmond, Frank, Stephan, Sumerauer, David, Scheurlen, Wolfram, Ryzhova, Marina V, Milde, Till, Kratz, Christian P, Samuel, David, Zhang, Jinghui, Solomon, David A, Marra, Marco, Eils, Roland, Bartram, Claus R, von Hoff, Katja, Rutkowski, Stefan, Ramaswamy, Vijay, Gilbertson, Richard J, Korshunov, Andrey, Taylor, Michael D, Lichter, Peter, Malkin, David, Gajjar, Amar, Korbel, Jan O, and Pfister, Stefan M
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Humans ,Medulloblastoma ,Cerebellar Neoplasms ,Genetic Predisposition to Disease ,Risk Factors ,Retrospective Studies ,Prospective Studies ,Reproducibility of Results ,Predictive Value of Tests ,Gene Expression Profiling ,Pedigree ,DNA Mutational Analysis ,DNA Methylation ,Heredity ,Phenotype ,Germ-Line Mutation ,Models ,Genetic ,Adolescent ,Adult ,Child ,Child ,Preschool ,Infant ,Female ,Male ,Young Adult ,Genetic Testing ,Transcriptome ,Biomarkers ,Tumor ,Progression-Free Survival ,Exome Sequencing ,Brain Cancer ,Genetics ,Cancer ,Human Genome ,Pediatric ,Pediatric Cancer ,Rare Diseases ,Brain Disorders ,Aetiology ,2.1 Biological and endogenous factors ,Oncology and Carcinogenesis ,Oncology & Carcinogenesis - Abstract
BackgroundMedulloblastoma is associated with rare hereditary cancer predisposition syndromes; however, consensus medulloblastoma predisposition genes have not been defined and screening guidelines for genetic counselling and testing for paediatric patients are not available. We aimed to assess and define these genes to provide evidence for future screening guidelines.MethodsIn this international, multicentre study, we analysed patients with medulloblastoma from retrospective cohorts (International Cancer Genome Consortium [ICGC] PedBrain, Medulloblastoma Advanced Genomics International Consortium [MAGIC], and the CEFALO series) and from prospective cohorts from four clinical studies (SJMB03, SJMB12, SJYC07, and I-HIT-MED). Whole-genome sequences and exome sequences from blood and tumour samples were analysed for rare damaging germline mutations in cancer predisposition genes. DNA methylation profiling was done to determine consensus molecular subgroups: WNT (MBWNT), SHH (MBSHH), group 3 (MBGroup3), and group 4 (MBGroup4). Medulloblastoma predisposition genes were predicted on the basis of rare variant burden tests against controls without a cancer diagnosis from the Exome Aggregation Consortium (ExAC). Previously defined somatic mutational signatures were used to further classify medulloblastoma genomes into two groups, a clock-like group (signatures 1 and 5) and a homologous recombination repair deficiency-like group (signatures 3 and 8), and chromothripsis was investigated using previously established criteria. Progression-free survival and overall survival were modelled for patients with a genetic predisposition to medulloblastoma.FindingsWe included a total of 1022 patients with medulloblastoma from the retrospective cohorts (n=673) and the four prospective studies (n=349), from whom blood samples (n=1022) and tumour samples (n=800) were analysed for germline mutations in 110 cancer predisposition genes. In our rare variant burden analysis, we compared these against 53 105 sequenced controls from ExAC and identified APC, BRCA2, PALB2, PTCH1, SUFU, and TP53 as consensus medulloblastoma predisposition genes according to our rare variant burden analysis and estimated that germline mutations accounted for 6% of medulloblastoma diagnoses in the retrospective cohort. The prevalence of genetic predispositions differed between molecular subgroups in the retrospective cohort and was highest for patients in the MBSHH subgroup (20% in the retrospective cohort). These estimates were replicated in the prospective clinical cohort (germline mutations accounted for 5% of medulloblastoma diagnoses, with the highest prevalence [14%] in the MBSHH subgroup). Patients with germline APC mutations developed MBWNT and accounted for most (five [71%] of seven) cases of MBWNT that had no somatic CTNNB1 exon 3 mutations. Patients with germline mutations in SUFU and PTCH1 mostly developed infant MBSHH. Germline TP53 mutations presented only in childhood patients in the MBSHH subgroup and explained more than half (eight [57%] of 14) of all chromothripsis events in this subgroup. Germline mutations in PALB2 and BRCA2 were observed across the MBSHH, MBGroup3, and MBGroup4 molecular subgroups and were associated with mutational signatures typical of homologous recombination repair deficiency. In patients with a genetic predisposition to medulloblastoma, 5-year progression-free survival was 52% (95% CI 40-69) and 5-year overall survival was 65% (95% CI 52-81); these survival estimates differed significantly across patients with germline mutations in different medulloblastoma predisposition genes.InterpretationGenetic counselling and testing should be used as a standard-of-care procedure in patients with MBWNT and MBSHH because these patients have the highest prevalence of damaging germline mutations in known cancer predisposition genes. We propose criteria for routine genetic screening for patients with medulloblastoma based on clinical and molecular tumour characteristics.FundingGerman Cancer Aid; German Federal Ministry of Education and Research; German Childhood Cancer Foundation (Deutsche Kinderkrebsstiftung); European Research Council; National Institutes of Health; Canadian Institutes for Health Research; German Cancer Research Center; St Jude Comprehensive Cancer Center; American Lebanese Syrian Associated Charities; Swiss National Science Foundation; European Molecular Biology Organization; Cancer Research UK; Hertie Foundation; Alexander and Margaret Stewart Trust; V Foundation for Cancer Research; Sontag Foundation; Musicians Against Childhood Cancer; BC Cancer Foundation; Swedish Council for Health, Working Life and Welfare; Swedish Research Council; Swedish Cancer Society; the Swedish Radiation Protection Authority; Danish Strategic Research Council; Swiss Federal Office of Public Health; Swiss Research Foundation on Mobile Communication; Masaryk University; Ministry of Health of the Czech Republic; Research Council of Norway; Genome Canada; Genome BC; Terry Fox Research Institute; Ontario Institute for Cancer Research; Pediatric Oncology Group of Ontario; The Family of Kathleen Lorette and the Clark H Smith Brain Tumour Centre; Montreal Children's Hospital Foundation; The Hospital for Sick Children: Sonia and Arthur Labatt Brain Tumour Research Centre, Chief of Research Fund, Cancer Genetics Program, Garron Family Cancer Centre, MDT's Garron Family Endowment; BC Childhood Cancer Parents Association; Cure Search Foundation; Pediatric Brain Tumor Foundation; Brainchild; and the Government of Ontario.
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- 2018
4. Family history of cancer and the risk of childhood brain tumors : a pooled analysis of the ESCALE and ESTELLE studies (SFCE)
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Bagazgoïtia, Nicolas Vidart d’Egurbide, Bailey, Helen D., Orsi, Laurent, Guerrini-Rousseau, Léa, Bertozzi, Anne-Isabelle, Faure-Conter, Cécile, Leblond, Pierre, Pellier, Isabelle, Freycon, Claire, Doz, François, Puget, Stéphanie, Ducassou, Stéphane, Lacour, Brigitte, and Clavel, Jacqueline
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- 2019
5. Traitement des douleurs de mucite : actualités et perspectives
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Guerrini-Rousseau, Léa, Marec-Berard, Perrine, Bolle, Stéphanie, and Laurent, Sophie
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- 2019
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6. Parental smoking, maternal alcohol, coffee and tea consumption and the risk of childhood brain tumours : the ESTELLE and ESCALE studies (SFCE, France)
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Bailey, Helen D., Lacour, Brigitte, Guerrini-Rousseau, Léa, Bertozzi, Anne-Isabelle, Leblond, Pierre, Faure-Conter, Cécile, Pellier, Isabelle, Freycon, Claire, Doz, François, Puget, Stéphanie, Ducassou, Stéphane, Orsi, Laurent, and Clavel, Jacqueline
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- 2017
7. Clinical outcome of pediatric medulloblastoma patients with Li–Fraumeni syndrome
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Kolodziejczak, Anna S, primary, Guerrini-Rousseau, Lea, additional, Planchon, Julien Masliah, additional, Ecker, Jonas, additional, Selt, Florian, additional, Mynarek, Martin, additional, Obrecht, Denise, additional, Sill, Martin, additional, Autry, Robert J, additional, Stutheit-Zhao, Eric, additional, Hirsch, Steffen, additional, Amouyal, Elsa, additional, Dufour, Christelle, additional, Ayrault, Olivier, additional, Torrejon, Jacob, additional, Waszak, Sebastian M, additional, Ramaswamy, Vijay, additional, Pentikainen, Virve, additional, Demir, Haci Ahmet, additional, Clifford, Steven C, additional, Schwalbe, Ed C, additional, Massimi, Luca, additional, Snuderl, Matija, additional, Galbraith, Kristyn, additional, Karajannis, Matthias A, additional, Hill, Katherine, additional, Li, Bryan K, additional, Walsh, Mike, additional, White, Christine L, additional, Redmond, Shelagh, additional, Loizos, Loizou, additional, Jakob, Marcus, additional, Kordes, Uwe R, additional, Schmid, Irene, additional, Hauer, Julia, additional, Blattmann, Claudia, additional, Filippidou, Maria, additional, Piccolo, Gianluca, additional, Scheurlen, Wolfram, additional, Farrag, Ahmed, additional, Grund, Kerstin, additional, Sutter, Christian, additional, Pietsch, Torsten, additional, Frank, Stephan, additional, Schewe, Denis M, additional, Malkin, David, additional, Ben-Arush, Myriam, additional, Sehested, Astrid, additional, Wong, Tai-Tong, additional, Wu, Kuo-Sheng, additional, Liu, Yen-Lin, additional, Carceller, Fernando, additional, Mueller, Sabine, additional, Stoller, Schuyler, additional, Taylor, Michael D, additional, Tabori, Uri, additional, Bouffet, Eric, additional, Kool, Marcel, additional, Sahm, Felix, additional, von Deimling, Andreas, additional, Korshunov, Andrey, additional, von Hoff, Katja, additional, Kratz, Christian P, additional, Sturm, Dominik, additional, Jones, David T W, additional, Rutkowski, Stefan, additional, van Tilburg, Cornelis M, additional, Witt, Olaf, additional, Bougeard, Gaëlle, additional, Pajtler, Kristian W, additional, Pfister, Stefan M, additional, Bourdeaut, Franck, additional, and Milde, Till, additional
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- 2023
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8. Mismatch Repair Deficiency and Lynch Syndrome Among Adult Patients With Glioma
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Benusiglio, Patrick R., primary, Elder, Fikret, additional, Touat, Mehdi, additional, Perrier, Alexandre, additional, Sanson, Marc, additional, Colas, Chrystelle, additional, Guerrini-Rousseau, Lea, additional, Tran, Duy Thanh, additional, Trabelsi, Nesrine, additional, Carpentier, Catherine, additional, Marie, Yannick, additional, Adam, Clovis, additional, Bernier, Michèle, additional, Cazals-Hatem, Dominique, additional, Mokhtari, Karima, additional, Tran, Suzanne, additional, Mathon, Bertrand, additional, Capelle, Laurent, additional, Dhooge, Marion, additional, Idbaih, Ahmed, additional, Alentorn, Agusti, additional, Houillier, Caroline, additional, Dehais, Caroline, additional, Hoang-Xuan, Khe, additional, Cuzzubbo, Stefania, additional, Carpentier, Antoine, additional, Duval, Alex, additional, Coulet, Florence, additional, and Bielle, Franck, additional
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- 2023
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9. Etude neuroradiologique du syndrome CMMRD et comparaison en imagerie de tumeurs gliales de haut grade selon le statut MMR
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Raveneau, Magali, primary, Dangouloff-Ross, Volodia, additional, Roux, Charles-Joris, additional, Levy, Raphael, additional, Guerrini-Rousseau, Lea, additional, Sevely, Annick, additional, Darcourt, Jean, additional, Bonneville, Fabrice, additional, and Boddaert, Nathalie, additional
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- 2023
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10. Cognitive Profile of Children With Intracranial Germ Cell Tumor According to Tumor Location
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Coutinho, Virginie, Dellatolas, Georges, Castaignede-Lalande, Clemence, Longaud-Vales, Audrey, Kieffer, Virginie, Guerrini-Rousseau, Lea, Grill, Jacques, Valteau-Couanet, Dominique, and Dufour, Christelle
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- 2018
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11. EPID-04. PREDCAP, the French registry of predisposition to pediatric cancers
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Guerrini-Rousseau, Lea, primary, Hoarau, Pauline, additional, Bougeard, Gaelle, additional, Golmard, Lisa, additional, Colas, Chrystelle, additional, Gauthier-Villars, Marion, additional, Houdayer, Claude, additional, Frebourg, Thierry, additional, Bourdeaut, Franck, additional, and Brugieres, Laurence, additional
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- 2022
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12. HGG-41. Glioma oncogenesis in the constitutional mismatch repair deficiency (CMMRD) syndrome
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Guerrini-Rousseau, Lea, primary, Merlevede, Jane, additional, Denizeau, Philippe, additional, Andrejuolo, Felipe, additional, Varlet, Pascale, additional, Puget, Stephanie, additional, Beccaria, Kevin, additional, Blauwblomme, Thomas, additional, Cabaret, Odile, additional, Hamzaoui, Nadim, additional, Bourdeaut, Franck, additional, Faure-Conter, Cecile, additional, Muleris, Martine, additional, Colas, Chrystelle, additional, de Beaumais, Tiphaine Adam, additional, Castel, David, additional, Rouleau, Etienne, additional, Brugieres, Laurence, additional, Grill, Jacques, additional, and Debily, Marie-Anne, additional
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- 2022
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13. MEDB-14. Clinical outcome of pediatric medulloblastoma patients with Li-Fraumeni syndrome
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Kolodziejczak, Anna, primary, Guerrini-Rousseau, Lea, additional, Planchon, Julien Masliah, additional, Ecker, Jonas, additional, Selt, Florian, additional, Mynarek, Martin, additional, Obrecht, Denise, additional, Sill, Martin, additional, Hirsch, Steffen, additional, Sturm, Dominik, additional, Waszak, Sebastian M, additional, Ramaswamy, Vijay, additional, Pentikainen, Virve, additional, Demir, Haci Ahmet, additional, Clifford, Steven C, additional, Schwalbe, Ed, additional, Massimi, Luca, additional, Snuderl, Matija, additional, Galbraith, Kristyn, additional, Karajannis, Matthias A, additional, Hill, Katie, additional, Li, Bryan, additional, White, Christine L, additional, Redmond, Shelagh, additional, Loizos, Loizou, additional, Jakob, Marcus, additional, Kordes, Uwe, additional, Schmid, Irene, additional, Hauer, Julia, additional, Blattmann, Claudia, additional, Filippidou, Maria, additional, Scheurlen, Wolfram, additional, Kontny, Udo, additional, Grund, Kerstin, additional, Sutter, Christian, additional, Pietsch, Torsten, additional, van Tilburg, Cornelis M, additional, Frank, Stephan, additional, Schewe, Denis M, additional, Malkin, David, additional, Taylor, Michael D, additional, Tabori, Uri, additional, Bouffet, Eric, additional, Kool, Marcel, additional, Sahm, Felix, additional, von Deimling, Andreas, additional, Korshunov, Andrey, additional, Von Hoff, Katja, additional, Kratz, Christian, additional, Jones, David T W, additional, Rutkowski, Stefan, additional, Witt, Olaf, additional, Bougeard, Gaelle, additional, Pajtler, Kristian W, additional, Pfister, Stefan M, additional, Bourdeaut, Franck, additional, and Milde, Till, additional
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- 2022
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14. HGG-40. NF1 mosaicism in a CMMRD-patient with a glioblastoma
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Guerrini-Rousseau, Lea, primary, Cabaret, Odile, additional, Muleris, Martine, additional, Vidaud, Dominique, additional, Cotteret, Sophie, additional, Rouleau, Etienne, additional, de Beaumais, Tiphaine Adam, additional, Varlet, Pascale, additional, Morscher, Raphael, additional, Abbou, Samuel, additional, Dufour, Christelle, additional, Brugieres, Laurence, additional, and Grill, Jacques, additional
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- 2022
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15. Clinical outcome of pediatric medulloblastoma patients with Li-Fraumeni syndrome
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Kolodziejczak, Anna, Guerrini-Rousseau, Lea, Planchon, Julien Masliah, Ecker, Jonas, Selt, Florian, Mynarek, Martin, Obrecht, Denise, Sill, Martin, Hirsch, Steffen, Sturm, Dominik, Waszak, Sebastian M., Ramaswamy, Vijay, Pentikainen, Virve, Demir, Haci Ahmet, Clifford, Steven C., Schwalbe, Ed, Massimi, Luca, Snuderl, Matija, Galbraith, Kristyn, Karajannis, Matthias A., Hill, Katie, Li, Bryan, White, Christine L., Redmond, Shelagh, Loizos, Loizou, Jakob, Marcus, Kordes, Uwe, Schmid, Irene, Hauer, Julia, Blattmann, Claudia, Filippidou, Maria, Scheurlen, Wolfram, Kontny, Hans Udo, Grund, Kerstin, Sutter, Christian, Pietsch, Torsten, van Tilburg, Cornelis M., Frank, Stephan, Schewe, Denis M., Malkin, David, Taylor, Michael D., Tabori, Uri, Bouffet, Eric, Kool, Marcel, Sahm, Felix, Von Deimling, Andreas, Korshunov, Andrey, Von Hoff, Katja, Kratz, Christian, Jones, David T. W., Rutkowski, Stefan, Witt, Olaf, Bougeard, Gaelle, Pajtler, Kristian W., Pfister, Stefan M., Bourdeaut, Franck, and Milde, Till
- Abstract
20. International Symposium on Pediatric Neuro-Oncology, ISPNO 2022, Hamburg, Germany, 12 Jun 2022 - 15 Jun 2022; Neuro-Oncology : official journal of the World Federation of Neuro-Oncology 24(Supplement_1), MEDB-14 (2022). doi:10.1093/neuonc/noac079.389 special issue: "Abstracts from the 20th International Symposium on Pediatric Neuro-Oncology (ISPNO 2022)", Published by Oxford Univ. Press, Oxford
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- 2022
16. Low-dose ketamine adjuvant treatment for refractory pain in children, adolescents and young adults with cancer: a pilot study.
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Courade, Magali, Bertrand, Amandine, Guerrini-Rousseau, Lea, Pagnier, Anne, Levy, Dominique, Lervat, Cyril, Cojean, Nadine, Ribrault, Alice, Dugue, Sophie, Thouvenin, Sandrine, Piguet, Christophe, Schmitt, Claudine, and Marec-Berard, Perrine
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- 2022
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17. End-of-life care in children and adolescents with cancer: perspectives from a French pediatric oncology care network
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Blais, Sophie, primary, Cohen-Gogo, Sarah, additional, Gouache, Elodie, additional, Guerrini-Rousseau, Lea, additional, Brethon, Benoit, additional, Rahal, Ilhem, additional, Petit, Arnaud, additional, Raimondo, Graziella, additional, Pellegrino, Beatrice, additional, and Orbach, Daniel, additional
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- 2021
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18. Predisposition to cancer in children and adolescents
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Genetica Klinische Genetica, Child Health, Cancer, Kratz, Christian P, Jongmans, Marjolijn C, Cavé, Hélène, Wimmer, Katharina, Behjati, Sam, Guerrini-Rousseau, Lea, Milde, Till, Pajtler, Kristian W, Golmard, Lisa, Gauthier-Villars, Marion, Jewell, Rosalyn, Duncan, Catriona, Maher, Eamonn R, Brugieres, Laurence, Pritchard-Jones, Kathy, Bourdeaut, Franck, Genetica Klinische Genetica, Child Health, Cancer, Kratz, Christian P, Jongmans, Marjolijn C, Cavé, Hélène, Wimmer, Katharina, Behjati, Sam, Guerrini-Rousseau, Lea, Milde, Till, Pajtler, Kristian W, Golmard, Lisa, Gauthier-Villars, Marion, Jewell, Rosalyn, Duncan, Catriona, Maher, Eamonn R, Brugieres, Laurence, Pritchard-Jones, Kathy, and Bourdeaut, Franck
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- 2021
19. Predisposition to cancer in children and adolescents
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Kratz, Christian P, primary, Jongmans, Marjolijn C, additional, Cavé, Hélène, additional, Wimmer, Katharina, additional, Behjati, Sam, additional, Guerrini-Rousseau, Lea, additional, Milde, Till, additional, Pajtler, Kristian W, additional, Golmard, Lisa, additional, Gauthier-Villars, Marion, additional, Jewell, Rosalyn, additional, Duncan, Catriona, additional, Maher, Eamonn R, additional, Brugieres, Laurence, additional, Pritchard-Jones, Kathy, additional, and Bourdeaut, Franck, additional
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- 2021
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20. Germline Mutations Predispose to Pediatric Medulloblastoma
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Begemann, Matthias, Waszak, Sebastian M., Brugieres, Laurence, Varlet, Pascale, Pietsch, Torsten, Bowers, Daniel C., Chintagumpala, Murali, Sahm, Felix, Korbel, Jan O., Rutkowski, Stefan, Eggermann, Thomas, Gajjar, Amar, Robinson, Giles W., Northcott, Paul, Elbracht, Miriam, Pfister, Stefan M., Kontny, Udo, Kontny, Hans Udo, Jäger, Natalie, Sharma, Tanvi, Knopp, Cordula, Kraft, Florian, Moser, Olga, Mynarek, Martin, and Guerrini-Rousseau, Lea
- Abstract
Journal of clinical oncology : JCO 38(1), 43-50 (2020). doi:10.1200/JCO.19.00577, Published by American Society of Clinical Oncology, Alexandria, Va.
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- 2020
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21. GCT-29. DOES TUMOUR MARKER DECLINE PREDICT OUTCOME IN INTRACRANIAL NON-GERMINOMATOUS GERM CELL TUMOURS (NGGCTs)?
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Conter, Cecile Faure, primary, Lardy-Cleaud, Audrey, additional, Murray, Matthew, additional, Nicholson, James, additional, Guerrini-Rousseau, Lea, additional, Palenzuela, Gilles, additional, Alapetite, Claire, additional, Garre, Maria Louise, additional, Kortmann, Rolf, additional, Saran, Frank, additional, Ajithkumar, Thankamma, additional, Pietsch, Torsten, additional, Vasiljevic, Alexandre, additional, Ricardi, Umberto, additional, Timmermann, Beate, additional, Muller, Jans Enno, additional, and Calaminus, Gabriele, additional
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- 2020
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22. Relapsing intracranial germ cell tumours warrant retreatment
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Callec, Laetitia, primary, Lardy-Cleaud, Audrey, additional, Guerrini-Rousseau, Lea, additional, Alapetite, Claire, additional, Vignon, Laure, additional, Chastagner, Pascal, additional, Frappaz, Didier, additional, and Faure-Conter, Cecile, additional
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- 2020
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23. Germline GPR161 Mutations Predispose to Pediatric Medulloblastoma
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Begemann, Matthias, primary, Waszak, Sebastian M., additional, Robinson, Giles W., additional, Jäger, Natalie, additional, Sharma, Tanvi, additional, Knopp, Cordula, additional, Kraft, Florian, additional, Moser, Olga, additional, Mynarek, Martin, additional, Guerrini-Rousseau, Lea, additional, Brugieres, Laurence, additional, Varlet, Pascale, additional, Pietsch, Torsten, additional, Bowers, Daniel C., additional, Chintagumpala, Murali, additional, Sahm, Felix, additional, Korbel, Jan O., additional, Rutkowski, Stefan, additional, Eggermann, Thomas, additional, Gajjar, Amar, additional, Northcott, Paul, additional, Elbracht, Miriam, additional, Pfister, Stefan M., additional, Kontny, Udo, additional, and Kurth, Ingo, additional
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- 2020
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24. End-of-life care in children and adolescents with cancer: perspectives from a French pediatric oncology care network
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Blais, Sophie, Cohen-Gogo, Sarah, Gouache, Elodie, Guerrini-Rousseau, Lea, Brethon, Benoit, Rahal, Ilhem, Petit, Arnaud, Raimondo, Graziella, Pellegrino, Beatrice, and Orbach, Daniel
- Abstract
Background: In developed countries, cancer remains the leading cause of pediatric death from illness after the neonatal period.Objective: To describe the end-of-life care characteristics of children and adolescents with solid tumors (ST) or hematologic malignancies (HM) who died from tumor progression in the Île-de-France area.Methods: This is a regional, multicentric, retrospective review of medical files of all children and adolescents with cancer who died over a 1-year period. Extensive data from the last 3 months of life were collected.Results: A total of 99 eligible patients died at a median age of 9.8 years (range, 0.3–24 years). The most frequent terminal symptoms were pain (n = 86), fatigue (n = 84), dyspnea (n = 49), and anorexia (n = 41). Median number of medications per patient was 8 (range, 3–18). Patients required administration of opioids (n = 91), oxygen (n = 36), and/or sedation (n = 61). Decision for palliative care was present in all medical records and do-not-resuscitate orders in 90/99 cases. Symptom prevalence was comparable between children and adolescents with ST and HM. A wish regarding the place of death had been expressed for 64 patients and could be respected in 42 cases. Death occurred in hospital for 75 patients.Conclusions: This study represents a large and informative cohort illustrating current pediatric palliative care approaches in pediatric oncology. End-of-life remains an active period of care requiring coordination of multiple care teams.
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- 2022
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25. Low-dose ketamine adjuvant treatment for refractory pain in children, adolescents and young adults with cancer: a pilot study
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Courade, Magali, primary, Bertrand, Amandine, additional, Guerrini-Rousseau, Lea, additional, Pagnier, Anne, additional, Levy, Dominique, additional, Lervat, Cyril, additional, Cojean, Nadine, additional, Ribrault, Alice, additional, Dugue, Sophie, additional, Thouvenin, Sandrine, additional, Piguet, Christophe, additional, Schmitt, Claudine, additional, and Marec-Berard, Perrine, additional
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- 2019
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26. New stratification for early childhood medulloblastoma
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Guerrini-Rousseau, Lea, primary, Grill, Jacques, additional, and Dufour, Christelle, additional
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- 2018
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27. Spectrum and prevalence of genetic predisposition in medulloblastoma:a retrospective genetic study and prospective validation in a clinical trial cohort
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Waszak, Sebastian M., Northcott, Paul A., Buchhalter, Ivo, Robinson, Giles W., Sutter, Christian, Groebner, Susanne, Grund, Kerstin B., Brugières, Laurence, Jones, David T.W., Pajtler, Kristian W., Morrissy, A. Sorana, Kool, Marcel, Sturm, Dominik, Chavez, Lukas, Ernst, Aurelie, Brabetz, Sebastian, Hain, Michael, Zichner, Thomas, Segura-Wang, Maia, Weischenfeldt, Joachim, Rausch, Tobias, Mardin, Balca R., Zhou, Xin, Baciu, Cristina, Lawerenz, Christian, Chan, Jennifer A., Varlet, Pascale, Guerrini-Rousseau, Lea, Fults, Daniel W., Grajkowska, Wiesława, Hauser, Peter, Jabado, Nada, Ra, Young Shin, Zitterbart, Karel, Shringarpure, Suyash S., De La Vega, Francisco M., Bustamante, Carlos D., Ng, Ho Keung, Perry, Arie, MacDonald, Tobey J., Hernáiz Driever, Pablo, Bendel, Anne E., Bowers, Daniel C., McCowage, Geoffrey, Chintagumpala, Murali M., Cohn, Richard, Hassall, Timothy, Fleischhack, Gudrun, Eggen, Tone, Wesenberg, Finn, Feychting, Maria, Lannering, Birgitta, Schüz, Joachim, Johansen, Christoffer, Andersen, Tina V., Röösli, Martin, Kuehni, Claudia E., Grotzer, Michael, Kjaerheim, Kristina, Monoranu, Camelia M., Archer, Tenley C., Duke, Elizabeth, Pomeroy, Scott L., Shelagh, Redmond, Frank, Stephan, Sumerauer, David, Scheurlen, Wolfram, Ryzhova, Marina V., Milde, Till, Kratz, Christian P., Samuel, David, Zhang, Jinghui, Solomon, David A., Marra, Marco, Eils, Roland, Bartram, Claus R., von Hoff, Katja, Rutkowski, Stefan, Ramaswamy, Vijay, Gilbertson, Richard J., Korshunov, Andrey, Taylor, Michael D., Lichter, Peter, Malkin, David, Gajjar, Amar, Korbel, Jan O., Pfister, Stefan M., Waszak, Sebastian M., Northcott, Paul A., Buchhalter, Ivo, Robinson, Giles W., Sutter, Christian, Groebner, Susanne, Grund, Kerstin B., Brugières, Laurence, Jones, David T.W., Pajtler, Kristian W., Morrissy, A. Sorana, Kool, Marcel, Sturm, Dominik, Chavez, Lukas, Ernst, Aurelie, Brabetz, Sebastian, Hain, Michael, Zichner, Thomas, Segura-Wang, Maia, Weischenfeldt, Joachim, Rausch, Tobias, Mardin, Balca R., Zhou, Xin, Baciu, Cristina, Lawerenz, Christian, Chan, Jennifer A., Varlet, Pascale, Guerrini-Rousseau, Lea, Fults, Daniel W., Grajkowska, Wiesława, Hauser, Peter, Jabado, Nada, Ra, Young Shin, Zitterbart, Karel, Shringarpure, Suyash S., De La Vega, Francisco M., Bustamante, Carlos D., Ng, Ho Keung, Perry, Arie, MacDonald, Tobey J., Hernáiz Driever, Pablo, Bendel, Anne E., Bowers, Daniel C., McCowage, Geoffrey, Chintagumpala, Murali M., Cohn, Richard, Hassall, Timothy, Fleischhack, Gudrun, Eggen, Tone, Wesenberg, Finn, Feychting, Maria, Lannering, Birgitta, Schüz, Joachim, Johansen, Christoffer, Andersen, Tina V., Röösli, Martin, Kuehni, Claudia E., Grotzer, Michael, Kjaerheim, Kristina, Monoranu, Camelia M., Archer, Tenley C., Duke, Elizabeth, Pomeroy, Scott L., Shelagh, Redmond, Frank, Stephan, Sumerauer, David, Scheurlen, Wolfram, Ryzhova, Marina V., Milde, Till, Kratz, Christian P., Samuel, David, Zhang, Jinghui, Solomon, David A., Marra, Marco, Eils, Roland, Bartram, Claus R., von Hoff, Katja, Rutkowski, Stefan, Ramaswamy, Vijay, Gilbertson, Richard J., Korshunov, Andrey, Taylor, Michael D., Lichter, Peter, Malkin, David, Gajjar, Amar, Korbel, Jan O., and Pfister, Stefan M.
- Abstract
Background: Medulloblastoma is associated with rare hereditary cancer predisposition syndromes; however, consensus medulloblastoma predisposition genes have not been defined and screening guidelines for genetic counselling and testing for paediatric patients are not available. We aimed to assess and define these genes to provide evidence for future screening guidelines. Methods: In this international, multicentre study, we analysed patients with medulloblastoma from retrospective cohorts (International Cancer Genome Consortium [ICGC] PedBrain, Medulloblastoma Advanced Genomics International Consortium [MAGIC], and the CEFALO series) and from prospective cohorts from four clinical studies (SJMB03, SJMB12, SJYC07, and I-HIT-MED). Whole-genome sequences and exome sequences from blood and tumour samples were analysed for rare damaging germline mutations in cancer predisposition genes. DNA methylation profiling was done to determine consensus molecular subgroups: WNT (MBWNT), SHH (MBSHH), group 3 (MBGroup3), and group 4 (MBGroup4). Medulloblastoma predisposition genes were predicted on the basis of rare variant burden tests against controls without a cancer diagnosis from the Exome Aggregation Consortium (ExAC). Previously defined somatic mutational signatures were used to further classify medulloblastoma genomes into two groups, a clock-like group (signatures 1 and 5) and a homologous recombination repair deficiency-like group (signatures 3 and 8), and chromothripsis was investigated using previously established criteria. Progression-free survival and overall survival were modelled for patients with a genetic predisposition to medulloblastoma. Findings: We included a total of 1022 patients with medulloblastoma from the retrospective cohorts (n=673) and the four prospective studies (n=349), from whom blood samples (n=1022) and tumour samples (n=800) were analysed for germline mutations in 110 cancer predisposition genes. In
- Published
- 2018
28. HGG-42. GLIOMA ONCOGENESIS IN CONSTITUTIONNAL MISMATCH REPAIR DEFICIENCY (CMMRD) SYNDROME: A CLINICO-PATHOLOGICAL AND MOLECULAR STUDY IN 15 PATIENTS
- Author
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Merlevede, Jane, primary, Andreiuolo, Felipe, additional, Debily, Marie-Anne, additional, Guerrini-Rousseau, Lea, additional, Picot, Stephanie, additional, Barret, Emilie, additional, Lavoine, Noémie, additional, Castel, David, additional, Puget, Stephanie, additional, Brugieres, Laurence, additional, Varlet, Pascale, additional, and Grill, Jacques, additional
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- 2018
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29. Les auteurs
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Aulagner, Gilles, Cazin, Jean-Louis, Lemare, François, Limat, Samuel, Armoiry, Xavier, Astier, Alain, Barbier, Garance, Bardin, Christophe, Boiteux-Jurain, Marie, Boulin, Mathieu, Brunie, Vanida, Burtin, Christophe, Capelle, Aude, Chaigneau, Loïc, Chenailler, Catherine, Chinot, Olivier, Clairet, Anne-Laure, Correard, Florian, Daguindau, Étienne, Dahan, Muriel, Dansin, Éric, Debordeaux, Frédéric, Demoré, Béatrice, Desmaris, Romain, Dussart, Claude, Estève, Marie-Anne, Fagnoni, Philippe, Faucitano, Alexia, Faure, Pierre, Favé, Sophie, Fernandez, Christine, Gaillard, Claire, Goldwasser, François, Govindoorazoo, Axel, Gueneau, Pauline, Guerrini-Rousseau, Léa, Guyotat, Denis, Henaine, Anne-Marie, Honoré, Stéphane, Jary, Marine, Jeannin, Marie, Jonchere, Gabrielle, Kalbacher, Elsa, Kroemer, Marie, Kuzzay, Marie-Pierre, Levêque, Dominique, Madelaine, Isabelle, Mansi, Laura, Mimoun, Aguirre, Mongaret, Céline, Nerich, Virginie, Noirez, Véronique, Penel, Nicolas, Piketty, Anne-Catherine, Pistre, Pauline, Puisset, Florent, Rizzo-Padoin, Nathalie, Roy, Pétronille, Sautou, Valérie, Servent, Véronique, Slimano, Florian, Spiesser-Robelet, Laurence, Thiery-Vuillemin, Antoine, Thomas-Schoemann, Audrey, Tournamille, Jean-François, Valteau-Couanet, Dominique, Vienot, Angélique, Vigneron, Jean, Villeminey, Clémentine, Vinson, Camille, Braguer, Diane, Chaigneau, Aurélie, Chaussard, Michaël, Demirdjian, Sylvie, Gaudin, Amélie, Guénée de Courtivron, Charlotte, Hosten, Benoît, Morel, Daphné, Opsomer, Marie-Agnès, Petit, Marie, and Pinel, Sylvine
- Published
- 2020
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30. Liste des collaborateurs
- Author
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Armoiry, Xavier, Astier, Alain, Aulagner, Gilles, Bardin, Christophe, Bichard, Damien, Boulin, Mathieu, Braguer, Diane, Breilh, Dominique, Brunie, Vanida, Burtin, Christophe, Cazin, Jean-Louis, Chaigneau, Aurélie, Chaussard, Michaël, Chenailler, Catherine, Chinot, Olivier, de Courtivron, Charlotte, Dahan, Muriel, Dansin, Éric, Demirdjian, Sylvie, Demoré, Béatrice, Desmaris, Romain-Pacôme, Estève, Marie-Anne, Fagnoni, Philippe, Faure, Pierre, Fernandez, Christine, Gaudin, Amélie, Guerrini-Rousseau, Léa, Goldwasser, François, Honoré, Stéphane, Hosten, Benoît, Kalbacher, Elsa, Kuzzay, Marie-Pierre, Latour, Jean-François, Lemare, François, Lévêque, Dominique, Limat, Samuel, Madelaine, Isabelle, Mateus, Christine, Mimoun, Aguirre, Mongaret, Céline, Morel, Daphné, Nerich, Virginie, Noé, Gaëlle, Noirez, Véronique, Opsomer, Marie-Agnès, Penel, Nicolas, Petit, Marie, Pinel, Sylvine, Puisset, Florent, Rizzo-Padoin, Nathalie, Robert, Caroline, Sautou, Valérie, Servant, Vincent, Servent, Véronique, Spiesser-Robelet, Laurence, Thiery-Vuillemin, Antoine, Thomas-Schoemann, Audrey, Tournamille, Jean-François, Valteau-Couanet, Dominique, Vigneron, Jean, Voidey, Aline, and Xuereb, Fabien
- Published
- 2016
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31. Mesenchymal Transition and PDGFRA Amplification/Mutation Are Key Distinct Oncogenic Events in Pediatric Diffuse Intrinsic Pontine Gliomas
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Puget, Stephanie, primary, Philippe, Cathy, additional, Bax, Dorine A., additional, Job, Bastien, additional, Varlet, Pascale, additional, Junier, Marie-Pierre, additional, Andreiuolo, Felipe, additional, Carvalho, Dina, additional, Reis, Ricardo, additional, Guerrini-Rousseau, Lea, additional, Roujeau, Thomas, additional, Dessen, Philippe, additional, Richon, Catherine, additional, Lazar, Vladimir, additional, Le Teuff, Gwenael, additional, Sainte-Rose, Christian, additional, Geoerger, Birgit, additional, Vassal, Gilles, additional, Jones, Chris, additional, and Grill, Jacques, additional
- Published
- 2012
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32. Mesenchymal Transition and PDGFRA Amplification/ Mutation Are Key Distinct Oncogenic Events in Pediatric Diffuse Intrinsic Pontine Gliomas.
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Puget, Stephanie, Philippe, Cathy, Bax, Dorine A., Job, Bastien, Varlet, Pascale, Junier, Marie-Pierre, Andreiuolo, Felipe, Carvalho, Dina, Reis, Ricardo, Guerrini-Rousseau, Lea, Roujeau, Thomas, Dessen, Philippe, Richon, Catherine, Lazar, Vladimir, Teuff, Gwenael Le, Sainte-Rose, Christian, Geoerger, Birgit, Vassal, Gilles, Jones, Chris, and Grill, Jacques
- Subjects
BRAIN cancer ,MESENCHYMAL stem cells ,GENE expression ,RADIOTHERAPY ,BIOPSY - Abstract
Diffuse intrinsic pontine glioma (DIPG) is one of the most frequent malignant pediatric brain tumor and its prognosis is universaly fatal. No significant improvement has been made in last thirty years over the standard treatment with radiotherapy. To address the paucity of understanding of DIPGs, we have carried out integrated molecular profiling of a large series of samples obtained with stereotactic biopsy at diagnosis. While chromosomal imbalances did not distinguish DIPG and supratentorial tumors on CGHarrays, gene expression profiling revealed clear differences between them, with brainstem gliomas resembling midline/thalamic tumours, indicating a closely-related origin. Two distinct subgroups of DIPG were identified. The first subgroup displayed mesenchymal and pro-angiogenic characteristics, with stem cell markers enrichment consistent with the possibility to grow tumor stem cells from these biopsies. The other subgroup displayed oligodendroglial features, and appeared largely driven by PDGFRA, in particular through amplification and/or novel missense mutations in the extracellular domain. Patients in this later group had a significantly worse outcome with an hazard ratio for early deaths, ie before 10 months, 8 fold greater that the ones in the other subgroup (p = 0.041, Cox regression model). The worse outcome of patients with the oligodendroglial type of tumors was confirmed on a series of 55 paraffin-embedded biopsy samples at diagnosis (median OS of 7.73 versus 12.37 months, p = 0.045, log-rank test). Two distinct transcriptional subclasses of DIPG with specific genomic alterations can be defined at diagnosis by oligodendroglial differentiation or mesenchymal transition, respectively. Classifying these tumors by signal transduction pathway activation and by mutation in pathway member genes may be particularily valuable for the development of targeted therapies [ABSTRACT FROM AUTHOR]
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- 2012
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33. Spectrum and prevalence of genetic predisposition in medulloblastoma: a retrospective genetic study and prospective validation in a clinical trial cohort
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Waszak, Sebastian M, Northcott, Paul A, Buchhalter, Ivo, Robinson, Giles W, Sutter, Christian, Groebner, Susanne, Grund, Kerstin B, Brugières, Laurence, Jones, David TW, Pajtler, Kristian W, Morrissy, A Sorana, Kool, Marcel, Sturm, Dominik, Chavez, Lukas, Ernst, Aurelie, Brabetz, Sebastian, Hain, Michael, Zichner, Thomas, Segura-Wang, Maia, Weischenfeldt, Joachim, Rausch, Tobias, Mardin, Balca R, Zhou, Xin, Baciu, Cristina, Lawerenz, Christian, Chan, Jennifer A, Varlet, Pascale, Guerrini-Rousseau, Lea, Fults, Daniel W, Grajkowska, Wiesława, Hauser, Peter, Jabado, Nada, Ra, Young-Shin, Zitterbart, Karel, Shringarpure, Suyash S, De La Vega, Francisco M, Bustamante, Carlos D, Ng, Ho-Keung, Perry, Arie, MacDonald, Tobey J, Hernáiz Driever, Pablo, Bendel, Anne E, Bowers, Daniel C, McCowage, Geoffrey, Chintagumpala, Murali M, Cohn, Richard, Hassall, Timothy, Fleischhack, Gudrun, Eggen, Tone, Wesenberg, Finn, Feychting, Maria, Lannering, Birgitta, Schüz, Joachim, Johansen, Christoffer, Andersen, Tina V, Röösli, Martin, Kuehni, Claudia E, Grotzer, Michael, Kjaerheim, Kristina, Monoranu, Camelia M, Archer, Tenley C, Duke, Elizabeth, Pomeroy, Scott L, Shelagh, Redmond, Frank, Stephan, Sumerauer, David, Scheurlen, Wolfram, Ryzhova, Marina V, Milde, Till, Kratz, Christian P, Samuel, David, Zhang, Jinghui, Solomon, David A, Marra, Marco, Eils, Roland, Bartram, Claus R, Von Hoff, Katja, Rutkowski, Stefan, Ramaswamy, Vijay, Gilbertson, Richard J, Korshunov, Andrey, Taylor, Michael D, Lichter, Peter, Malkin, David, Gajjar, Amar, Korbel, Jan O, and Pfister, Stefan M
- Subjects
Adult ,Male ,Heredity ,Adolescent ,DNA Mutational Analysis ,Young Adult ,Predictive Value of Tests ,Risk Factors ,Exome Sequencing ,Biomarkers, Tumor ,Humans ,Genetic Predisposition to Disease ,Genetic Testing ,Prospective Studies ,Cerebellar Neoplasms ,Child ,Germ-Line Mutation ,Retrospective Studies ,Models, Genetic ,Gene Expression Profiling ,Infant ,Reproducibility of Results ,DNA Methylation ,Progression-Free Survival ,3. Good health ,Pedigree ,Phenotype ,Child, Preschool ,Female ,Transcriptome ,Medulloblastoma - Abstract
BACKGROUND: Medulloblastoma is associated with rare hereditary cancer predisposition syndromes; however, consensus medulloblastoma predisposition genes have not been defined and screening guidelines for genetic counselling and testing for paediatric patients are not available. We aimed to assess and define these genes to provide evidence for future screening guidelines. METHODS: In this international, multicentre study, we analysed patients with medulloblastoma from retrospective cohorts (International Cancer Genome Consortium [ICGC] PedBrain, Medulloblastoma Advanced Genomics International Consortium [MAGIC], and the CEFALO series) and from prospective cohorts from four clinical studies (SJMB03, SJMB12, SJYC07, and I-HIT-MED). Whole-genome sequences and exome sequences from blood and tumour samples were analysed for rare damaging germline mutations in cancer predisposition genes. DNA methylation profiling was done to determine consensus molecular subgroups: WNT (MBWNT), SHH (MBSHH), group 3 (MBGroup3), and group 4 (MBGroup4). Medulloblastoma predisposition genes were predicted on the basis of rare variant burden tests against controls without a cancer diagnosis from the Exome Aggregation Consortium (ExAC). Previously defined somatic mutational signatures were used to further classify medulloblastoma genomes into two groups, a clock-like group (signatures 1 and 5) and a homologous recombination repair deficiency-like group (signatures 3 and 8), and chromothripsis was investigated using previously established criteria. Progression-free survival and overall survival were modelled for patients with a genetic predisposition to medulloblastoma. FINDINGS: We included a total of 1022 patients with medulloblastoma from the retrospective cohorts (n=673) and the four prospective studies (n=349), from whom blood samples (n=1022) and tumour samples (n=800) were analysed for germline mutations in 110 cancer predisposition genes. In our rare variant burden analysis, we compared these against 53 105 sequenced controls from ExAC and identified APC, BRCA2, PALB2, PTCH1, SUFU, and TP53 as consensus medulloblastoma predisposition genes according to our rare variant burden analysis and estimated that germline mutations accounted for 6% of medulloblastoma diagnoses in the retrospective cohort. The prevalence of genetic predispositions differed between molecular subgroups in the retrospective cohort and was highest for patients in the MBSHH subgroup (20% in the retrospective cohort). These estimates were replicated in the prospective clinical cohort (germline mutations accounted for 5% of medulloblastoma diagnoses, with the highest prevalence [14%] in the MBSHH subgroup). Patients with germline APC mutations developed MBWNT and accounted for most (five [71%] of seven) cases of MBWNT that had no somatic CTNNB1 exon 3 mutations. Patients with germline mutations in SUFU and PTCH1 mostly developed infant MBSHH. Germline TP53 mutations presented only in childhood patients in the MBSHH subgroup and explained more than half (eight [57%] of 14) of all chromothripsis events in this subgroup. Germline mutations in PALB2 and BRCA2 were observed across the MBSHH, MBGroup3, and MBGroup4 molecular subgroups and were associated with mutational signatures typical of homologous recombination repair deficiency. In patients with a genetic predisposition to medulloblastoma, 5-year progression-free survival was 52% (95% CI 40-69) and 5-year overall survival was 65% (95% CI 52-81); these survival estimates differed significantly across patients with germline mutations in different medulloblastoma predisposition genes. INTERPRETATION: Genetic counselling and testing should be used as a standard-of-care procedure in patients with MBWNT and MBSHH because these patients have the highest prevalence of damaging germline mutations in known cancer predisposition genes. We propose criteria for routine genetic screening for patients with medulloblastoma based on clinical and molecular tumour characteristics. FUNDING: German Cancer Aid; German Federal Ministry of Education and Research; German Childhood Cancer Foundation (Deutsche Kinderkrebsstiftung); European Research Council; National Institutes of Health; Canadian Institutes for Health Research; German Cancer Research Center; St Jude Comprehensive Cancer Center; American Lebanese Syrian Associated Charities; Swiss National Science Foundation; European Molecular Biology Organization; Cancer Research UK; Hertie Foundation; Alexander and Margaret Stewart Trust; V Foundation for Cancer Research; Sontag Foundation; Musicians Against Childhood Cancer; BC Cancer Foundation; Swedish Council for Health, Working Life and Welfare; Swedish Research Council; Swedish Cancer Society; the Swedish Radiation Protection Authority; Danish Strategic Research Council; Swiss Federal Office of Public Health; Swiss Research Foundation on Mobile Communication; Masaryk University; Ministry of Health of the Czech Republic; Research Council of Norway; Genome Canada; Genome BC; Terry Fox Research Institute; Ontario Institute for Cancer Research; Pediatric Oncology Group of Ontario; The Family of Kathleen Lorette and the Clark H Smith Brain Tumour Centre; Montreal Children's Hospital Foundation; The Hospital for Sick Children: Sonia and Arthur Labatt Brain Tumour Research Centre, Chief of Research Fund, Cancer Genetics Program, Garron Family Cancer Centre, MDT's Garron Family Endowment; BC Childhood Cancer Parents Association; Cure Search Foundation; Pediatric Brain Tumor Foundation; Brainchild; and the Government of Ontario.
34. Spectrum and prevalence of genetic predisposition in medulloblastoma: a retrospective genetic study and prospective validation in a clinical trial cohort
- Author
-
Waszak, Sebastian M, Northcott, Paul A, Buchhalter, Ivo, Robinson, Giles W, Sutter, Christian, Groebner, Susanne, Grund, Kerstin B, Brugières, Laurence, Jones, David T W, Pajtler, Kristian W, Morrissy, A Sorana, Kool, Marcel, Sturm, Dominik, Chavez, Lukas, Ernst, Aurelie, Brabetz, Sebastian, Hain, Michael, Zichner, Thomas, Segura-Wang, Maia, Weischenfeldt, Joachim, Rausch, Tobias, Mardin, Balca R, Zhou, Xin, Baciu, Cristina, Lawerenz, Christian, Chan, Jennifer A, Varlet, Pascale, Guerrini-Rousseau, Lea, Fults, Daniel W, Grajkowska, Wiesława, Hauser, Peter, Jabado, Nada, Ra, Young-Shin, Zitterbart, Karel, Shringarpure, Suyash S, De La Vega, Francisco M, Bustamante, Carlos D, Ng, Ho-Keung, Perry, Arie, MacDonald, Tobey J, Hernáiz Driever, Pablo, Bendel, Anne E, Bowers, Daniel C, McCowage, Geoffrey, Chintagumpala, Murali M, Cohn, Richard, Hassall, Timothy, Fleischhack, Gudrun, Eggen, Tone, Wesenberg, Finn, Feychting, Maria, Lannering, Birgitta, Schüz, Joachim, Johansen, Christoffer, Andersen, Tina V, Röösli, Martin, Kuehni, Claudia E, Grotzer, Michael, Kjaerheim, Kristina, Monoranu, Camelia M, Archer, Tenley C, Duke, Elizabeth, Pomeroy, Scott L, Redmond, Shelagh, Frank, Stephan, Sumerauer, David, Scheurlen, Wolfram, Ryzhova, Marina V, Milde, Till, Kratz, Christian P, Samuel, David, Zhang, Jinghui, Solomon, David A, Marra, Marco, Eils, Roland, Bartram, Claus R, Von Hoff, Katja, Rutkowski, Stefan, Ramaswamy, Vijay, Gilbertson, Richard J, Korshunov, Andrey, Taylor, Michael D, Lichter, Peter, Malkin, David, Gajjar, Amar, Korbel, Jan O, and Pfister, Stefan M
- Subjects
610 Medicine & health ,360 Social problems & social services ,3. Good health - Abstract
BACKGROUND Medulloblastoma is associated with rare hereditary cancer predisposition syndromes; however, consensus medulloblastoma predisposition genes have not been defined and screening guidelines for genetic counselling and testing for paediatric patients are not available. We aimed to assess and define these genes to provide evidence for future screening guidelines. METHODS In this international, multicentre study, we analysed patients with medulloblastoma from retrospective cohorts (International Cancer Genome Consortium [ICGC] PedBrain, Medulloblastoma Advanced Genomics International Consortium [MAGIC], and the CEFALO series) and from prospective cohorts from four clinical studies (SJMB03, SJMB12, SJYC07, and I-HIT-MED). Whole-genome sequences and exome sequences from blood and tumour samples were analysed for rare damaging germline mutations in cancer predisposition genes. DNA methylation profiling was done to determine consensus molecular subgroups: WNT (MB), SHH (MB), group 3 (MB), and group 4 (MB). Medulloblastoma predisposition genes were predicted on the basis of rare variant burden tests against controls without a cancer diagnosis from the Exome Aggregation Consortium (ExAC). Previously defined somatic mutational signatures were used to further classify medulloblastoma genomes into two groups, a clock-like group (signatures 1 and 5) and a homologous recombination repair deficiency-like group (signatures 3 and 8), and chromothripsis was investigated using previously established criteria. Progression-free survival and overall survival were modelled for patients with a genetic predisposition to medulloblastoma. FINDINGS We included a total of 1022 patients with medulloblastoma from the retrospective cohorts (n=673) and the four prospective studies (n=349), from whom blood samples (n=1022) and tumour samples (n=800) were analysed for germline mutations in 110 cancer predisposition genes. In our rare variant burden analysis, we compared these against 53 105 sequenced controls from ExAC and identified APC, BRCA2, PALB2, PTCH1, SUFU, and TP53 as consensus medulloblastoma predisposition genes according to our rare variant burden analysis and estimated that germline mutations accounted for 6% of medulloblastoma diagnoses in the retrospective cohort. The prevalence of genetic predispositions differed between molecular subgroups in the retrospective cohort and was highest for patients in the MB subgroup (20% in the retrospective cohort). These estimates were replicated in the prospective clinical cohort (germline mutations accounted for 5% of medulloblastoma diagnoses, with the highest prevalence [14%] in the MB subgroup). Patients with germline APC mutations developed MB and accounted for most (five [71%] of seven) cases of MB that had no somatic CTNNB1 exon 3 mutations. Patients with germline mutations in SUFU and PTCH1 mostly developed infant MB. Germline TP53 mutations presented only in childhood patients in the MB subgroup and explained more than half (eight [57%] of 14) of all chromothripsis events in this subgroup. Germline mutations in PALB2 and BRCA2 were observed across the MB, MB, and MB molecular subgroups and were associated with mutational signatures typical of homologous recombination repair deficiency. In patients with a genetic predisposition to medulloblastoma, 5-year progression-free survival was 52% (95% CI 40-69) and 5-year overall survival was 65% (95% CI 52-81); these survival estimates differed significantly across patients with germline mutations in different medulloblastoma predisposition genes. INTERPRETATION Genetic counselling and testing should be used as a standard-of-care procedure in patients with MB and MB because these patients have the highest prevalence of damaging germline mutations in known cancer predisposition genes. We propose criteria for routine genetic screening for patients with medulloblastoma based on clinical and molecular tumour characteristics. FUNDING German Cancer Aid; German Federal Ministry of Education and Research; German Childhood Cancer Foundation (Deutsche Kinderkrebsstiftung); European Research Council; National Institutes of Health; Canadian Institutes for Health Research; German Cancer Research Center; St Jude Comprehensive Cancer Center; American Lebanese Syrian Associated Charities; Swiss National Science Foundation; European Molecular Biology Organization; Cancer Research UK; Hertie Foundation; Alexander and Margaret Stewart Trust; V Foundation for Cancer Research; Sontag Foundation; Musicians Against Childhood Cancer; BC Cancer Foundation; Swedish Council for Health, Working Life and Welfare; Swedish Research Council; Swedish Cancer Society; the Swedish Radiation Protection Authority; Danish Strategic Research Council; Swiss Federal Office of Public Health; Swiss Research Foundation on Mobile Communication; Masaryk University; Ministry of Health of the Czech Republic; Research Council of Norway; Genome Canada; Genome BC; Terry Fox Research Institute; Ontario Institute for Cancer Research; Pediatric Oncology Group of Ontario; The Family of Kathleen Lorette and the Clark H Smith Brain Tumour Centre; Montreal Children's Hospital Foundation; The Hospital for Sick Children: Sonia and Arthur Labatt Brain Tumour Research Centre, Chief of Research Fund, Cancer Genetics Program, Garron Family Cancer Centre, MDT's Garron Family Endowment; BC Childhood Cancer Parents Association; Cure Search Foundation; Pediatric Brain Tumor Foundation; Brainchild; and the Government of Ontario.
35. Glioma oncogenesis in the Constitutional mismatch repair deficiency (CMMRD) syndrome.
- Author
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Guerrini-Rousseau L, Merlevede J, Denizeau P, Andreiuolo F, Varlet P, Puget S, Beccaria K, Blauwblomme T, Cabaret O, Hamzaoui N, Bourdeaut F, Faure-Conter C, Muleris M, Colas C, Adam de Beaumais T, Castel D, Rouleau E, Brugières L, Grill J, and Debily MA
- Abstract
Background: Constitutional mismatch repair deficiency (CMMRD) is a cancer predisposition due to biallelic mutations in one of the mismatch repair (MMR) genes associated with early onset of cancers, especially high-grade gliomas. Our aim was to decipher the molecular specificities of these gliomas., Methods: Clinical, histopathological, and whole exome sequencing data were analyzed in 12 children with genetically proven CMMRD and a high-grade glioma., Results: PDL1 expression was present in immunohistochemistry in 50% of the samples. In 9 patients, the glioma harbored an ultra-hypermutated phenotype (104-635 coding single nucleotide variants (SNV) per Mb, median 204). Driver mutations in POLE and POLD1 exonuclease domains were described for 8 and 1 patients respectively and were always present in the mutation burst with the highest variant allele frequency (VAF). The mutational signatures were dominated by MMR-related ones and similar in the different mutation bursts of a same patient without subsequent enrichment of the mutation signatures with POL-driven ones. Median number of coding SNV with VAF above one of the driving polymerase mutation per Mb was 57 (17-191). Our findings suggest that somatic polymerase alterations does not entirely explain the ultra-hypermutant phenotype. SETD2 , TP53 , NF1 , EPHB2 , PRKDC, and DICER1 genes were frequently mutated with higher VAF than the deleterious somatic polymerase mutation., Conclusions: CMMRD-associated gliomas have a specific oncogenesis that does not involve usual pathways and mutations seen in sporadic pediatric or adult glioblastomas. Frequent alterations in other pathways such as MAPK may suggest the use of other targeted therapies along with PD1 inhibitors., Competing Interests: The authors have no commercial association that might pose or create the appearance of a conflict of interest with the information presented in the submitted manuscript., (© The Author(s) 2024. Published by Oxford University Press, the Society for Neuro-Oncology and the European Association of Neuro-Oncology.)
- Published
- 2024
- Full Text
- View/download PDF
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