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1. New Brain Tumor Entities Emerge from Molecular Classification of CNS-PNETs.

Author

Sturm, Dominik, Orr, Brent A, Toprak, Umut H, Hovestadt, Volker, Jones, David TW, Capper, David, Sill, Martin, Buchhalter, Ivo, Northcott, Paul A, Leis, Irina, Ryzhova, Marina, Koelsche, Christian, Pfaff, Elke, Allen, Sariah J, Balasubramanian, Gnanaprakash, Worst, Barbara C, Pajtler, Kristian W, Brabetz, Sebastian, Johann, Pascal D, Sahm, Felix, Reimand, Jüri, Mackay, Alan, Carvalho, Diana M, Remke, Marc, Phillips, Joanna J, Perry, Arie, Cowdrey, Cynthia, Drissi, Rachid, Fouladi, Maryam, Giangaspero, Felice, Łastowska, Maria, Grajkowska, Wiesława, Scheurlen, Wolfram, Pietsch, Torsten, Hagel, Christian, Gojo, Johannes, Lötsch, Daniela, Berger, Walter, Slavc, Irene, Haberler, Christine, Jouvet, Anne, Holm, Stefan, Hofer, Silvia, Prinz, Marco, Keohane, Catherine, Fried, Iris, Mawrin, Christian, Scheie, David, Mobley, Bret C, Schniederjan, Matthew J, Santi, Mariarita, Buccoliero, Anna M, Dahiya, Sonika, Kramm, Christof M, von Bueren, André O, von Hoff, Katja, Rutkowski, Stefan, Herold-Mende, Christel, Frühwald, Michael C, Milde, Till, Hasselblatt, Martin, Wesseling, Pieter, Rößler, Jochen, Schüller, Ulrich, Ebinger, Martin, Schittenhelm, Jens, Frank, Stephan, Grobholz, Rainer, Vajtai, Istvan, Hans, Volkmar, Schneppenheim, Reinhard, Zitterbart, Karel, Collins, V Peter, Aronica, Eleonora, Varlet, Pascale, Puget, Stephanie, Dufour, Christelle, Grill, Jacques, Figarella-Branger, Dominique, Wolter, Marietta, Schuhmann, Martin U, Shalaby, Tarek, Grotzer, Michael, van Meter, Timothy, Monoranu, Camelia-Maria, Felsberg, Jörg, Reifenberger, Guido, Snuderl, Matija, Forrester, Lynn Ann, Koster, Jan, Versteeg, Rogier, Volckmann, Richard, van Sluis, Peter, Wolf, Stephan, Mikkelsen, Tom, Gajjar, Amar, Aldape, Kenneth, Moore, Andrew S, Taylor, Michael D, and Jones, Chris

Subjects
Humans, Neuroectodermal Tumors, Central Nervous System Neoplasms, Trans-Activators, Proto-Oncogene Proteins, Tumor Suppressor Proteins, Repressor Proteins, Gene Expression Profiling, Signal Transduction, DNA Methylation, Gene Expression Regulation, Neoplastic, Amino Acid Sequence, Molecular Sequence Data, Child, Forkhead Transcription Factors, Neuroblastoma, Cancer, Pediatric, Neurosciences, Brain Disorders, Rare Diseases, Orphan Drug, Brain Cancer, Pediatric Research Initiative, Pediatric Cancer, Biological Sciences, Medical and Health Sciences, Developmental Biology
Abstract

Primitive neuroectodermal tumors of the central nervous system (CNS-PNETs) are highly aggressive, poorly differentiated embryonal tumors occurring predominantly in young children but also affecting adolescents and adults. Herein, we demonstrate that a significant proportion of institutionally diagnosed CNS-PNETs display molecular profiles indistinguishable from those of various other well-defined CNS tumor entities, facilitating diagnosis and appropriate therapy for patients with these tumors. From the remaining fraction of CNS-PNETs, we identify four new CNS tumor entities, each associated with a recurrent genetic alteration and distinct histopathological and clinical features. These new molecular entities, designated "CNS neuroblastoma with FOXR2 activation (CNS NB-FOXR2)," "CNS Ewing sarcoma family tumor with CIC alteration (CNS EFT-CIC)," "CNS high-grade neuroepithelial tumor with MN1 alteration (CNS HGNET-MN1)," and "CNS high-grade neuroepithelial tumor with BCOR alteration (CNS HGNET-BCOR)," will enable meaningful clinical trials and the development of therapeutic strategies for patients affected by poorly differentiated CNS tumors.

Published
2016

2. Divergent clonal selection dominates medulloblastoma at recurrence

Author

Morrissy, A Sorana, Garzia, Livia, Shih, David JH, Zuyderduyn, Scott, Huang, Xi, Skowron, Patryk, Remke, Marc, Cavalli, Florence MG, Ramaswamy, Vijay, Lindsay, Patricia E, Jelveh, Salomeh, Donovan, Laura K, Wang, Xin, Luu, Betty, Zayne, Kory, Li, Yisu, Mayoh, Chelsea, Thiessen, Nina, Mercier, Eloi, Mungall, Karen L, Ma, Yusanne, Tse, Kane, Zeng, Thomas, Shumansky, Karey, Roth, Andrew JL, Shah, Sohrab, Farooq, Hamza, Kijima, Noriyuki, Holgado, Borja L, Lee, John JY, Matan-Lithwick, Stuart, Liu, Jessica, Mack, Stephen C, Manno, Alex, Michealraj, KA, Nor, Carolina, Peacock, John, Qin, Lei, Reimand, Juri, Rolider, Adi, Thompson, Yuan Y, Wu, Xiaochong, Pugh, Trevor, Ally, Adrian, Bilenky, Mikhail, Butterfield, Yaron SN, Carlsen, Rebecca, Cheng, Young, Chuah, Eric, Corbett, Richard D, Dhalla, Noreen, He, An, Lee, Darlene, Li, Haiyan I, Long, William, Mayo, Michael, Plettner, Patrick, Qian, Jenny Q, Schein, Jacqueline E, Tam, Angela, Wong, Tina, Birol, Inanc, Zhao, Yongjun, Faria, Claudia C, Pimentel, José, Nunes, Sofia, Shalaby, Tarek, Grotzer, Michael, Pollack, Ian F, Hamilton, Ronald L, Li, Xiao-Nan, Bendel, Anne E, Fults, Daniel W, Walter, Andrew W, Kumabe, Toshihiro, Tominaga, Teiji, Collins, V Peter, Cho, Yoon-Jae, Hoffman, Caitlin, Lyden, David, Wisoff, Jeffrey H, Garvin, James H, Stearns, Duncan S, Massimi, Luca, Schüller, Ulrich, Sterba, Jaroslav, Zitterbart, Karel, Puget, Stephanie, Ayrault, Olivier, Dunn, Sandra E, Tirapelli, Daniela PC, Carlotti, Carlos G, Wheeler, Helen, Hallahan, Andrew R, Ingram, Wendy, MacDonald, Tobey J, Olson, Jeffrey J, Van Meir, Erwin G, Lee, Ji-Yeoun, and Wang, Kyu-Chang

Subjects
Pediatric, Biotechnology, Genetics, Brain Disorders, Human Genome, Brain Cancer, Rare Diseases, Cancer, Animals, Cerebellar Neoplasms, Clone Cells, Craniospinal Irradiation, DNA Mutational Analysis, Disease Models, Animal, Drosophila melanogaster, Female, Genome, Human, Humans, Male, Medulloblastoma, Mice, Molecular Targeted Therapy, Neoplasm Recurrence, Local, Radiotherapy, Image-Guided, Selection, Genetic, Signal Transduction, Xenograft Model Antitumor Assays, General Science & Technology
Abstract

The development of targeted anti-cancer therapies through the study of cancer genomes is intended to increase survival rates and decrease treatment-related toxicity. We treated a transposon-driven, functional genomic mouse model of medulloblastoma with 'humanized' in vivo therapy (microneurosurgical tumour resection followed by multi-fractionated, image-guided radiotherapy). Genetic events in recurrent murine medulloblastoma exhibit a very poor overlap with those in matched murine diagnostic samples (

Published
2016

3. Molecular Classification of Ependymal Tumors across All CNS Compartments, Histopathological Grades, and Age Groups

Author

Pajtler, Kristian W, Witt, Hendrik, Sill, Martin, Jones, David TW, Hovestadt, Volker, Kratochwil, Fabian, Wani, Khalida, Tatevossian, Ruth, Punchihewa, Chandanamali, Johann, Pascal, Reimand, Jüri, Warnatz, Hans-Jörg, Ryzhova, Marina, Mack, Steve, Ramaswamy, Vijay, Capper, David, Schweizer, Leonille, Sieber, Laura, Wittmann, Andrea, Huang, Zhiqin, van Sluis, Peter, Volckmann, Richard, Koster, Jan, Versteeg, Rogier, Fults, Daniel, Toledano, Helen, Avigad, Smadar, Hoffman, Lindsey M, Donson, Andrew M, Foreman, Nicholas, Hewer, Ekkehard, Zitterbart, Karel, Gilbert, Mark, Armstrong, Terri S, Gupta, Nalin, Allen, Jeffrey C, Karajannis, Matthias A, Zagzag, David, Hasselblatt, Martin, Kulozik, Andreas E, Witt, Olaf, Collins, V Peter, von Hoff, Katja, Rutkowski, Stefan, Pietsch, Torsten, Bader, Gary, Yaspo, Marie-Laure, von Deimling, Andreas, Lichter, Peter, Taylor, Michael D, Gilbertson, Richard, Ellison, David W, Aldape, Kenneth, Korshunov, Andrey, Kool, Marcel, and Pfister, Stefan M

Subjects
Biological Sciences, Biomedical and Clinical Sciences, Genetics, Cancer, Adaptor Proteins, Signal Transducing, Adolescent, Adult, Age Factors, Aged, Central Nervous System Neoplasms, Child, Child, Preschool, DNA Methylation, Ependymoma, Female, Gene Dosage, Gene Expression Profiling, Gene Fusion, Humans, Infant, Male, Middle Aged, Phosphoproteins, Transcription Factors, Transcription, Genetic, YAP-Signaling Proteins, Young Adult, Neurosciences, Oncology and Carcinogenesis, Oncology & Carcinogenesis, Biochemistry and cell biology, Oncology and carcinogenesis
Abstract

Ependymal tumors across age groups are currently classified and graded solely by histopathology. It is, however, commonly accepted that this classification scheme has limited clinical utility based on its lack of reproducibility in predicting patients' outcome. We aimed at establishing a uniform molecular classification using DNA methylation profiling. Nine molecular subgroups were identified in a large cohort of 500 tumors, 3 in each anatomical compartment of the CNS, spine, posterior fossa, supratentorial. Two supratentorial subgroups are characterized by prototypic fusion genes involving RELA and YAP1, respectively. Regarding clinical associations, the molecular classification proposed herein outperforms the current histopathological classification and thus might serve as a basis for the next World Health Organization classification of CNS tumors.

Published
2015

5. International Society Of Neuropathology--Haarlem consensus guidelines for nervous system tumor classification and grading.

Author

Louis, David N, Perry, Arie, Burger, Peter, Ellison, David W, Reifenberger, Guido, von Deimling, Andreas, Aldape, Kenneth, Brat, Daniel, Collins, V Peter, Eberhart, Charles, Figarella-Branger, Dominique, Fuller, Gregory N, Giangaspero, Felice, Giannini, Caterina, Hawkins, Cynthia, Kleihues, Paul, Korshunov, Andrey, Kros, Johan M, Beatriz Lopes, M, Ng, Ho-Keung, Ohgaki, Hiroko, Paulus, Werner, Pietsch, Torsten, Rosenblum, Marc, Rushing, Elisabeth, Soylemezoglu, Figen, Wiestler, Otmar, Wesseling, Pieter, and International Society Of Neuropathology--Haarlem

Subjects
International Society Of Neuropathology--Haarlem, Humans, Nervous System Neoplasms, Molecular Diagnostic Techniques, Severity of Illness Index, Astrocytoma, World Health Organization, atypical teratoid rhabdoid tumor, brain tumors, classification, glioblastoma, glioma, grading, medulloblastoma, oligodendroglioma, Neurology & Neurosurgery, Clinical Sciences, Neurosciences
Abstract

Major discoveries in the biology of nervous system tumors have raised the question of how non-histological data such as molecular information can be incorporated into the next World Health Organization (WHO) classification of central nervous system tumors. To address this question, a meeting of neuropathologists with expertise in molecular diagnosis was held in Haarlem, the Netherlands, under the sponsorship of the International Society of Neuropathology (ISN). Prior to the meeting, participants solicited input from clinical colleagues in diverse neuro-oncological specialties. The present "white paper" catalogs the recommendations of the meeting, at which a consensus was reached that incorporation of molecular information into the next WHO classification should follow a set of provided "ISN-Haarlem" guidelines. Salient recommendations include that (i) diagnostic entities should be defined as narrowly as possible to optimize interobserver reproducibility, clinicopathological predictions and therapeutic planning; (ii) diagnoses should be "layered" with histologic classification, WHO grade and molecular information listed below an "integrated diagnosis"; (iii) determinations should be made for each tumor entity as to whether molecular information is required, suggested or not needed for its definition; (iv) some pediatric entities should be separated from their adult counterparts; (v) input for guiding decisions regarding tumor classification should be solicited from experts in complementary disciplines of neuro-oncology; and (iv) entity-specific molecular testing and reporting formats should be followed in diagnostic reports. It is hoped that these guidelines will facilitate the forthcoming update of the fourth edition of the WHO classification of central nervous system tumors.

Published
2014

6. ISN‐Haarlem Brain Tumor Classification Guidelines

Author

Louis, David N, Perry, Arie, Burger, Peter, Ellison, David W, Reifenberger, Guido, von Deimling, Andreas, Aldape, Kenneth, Brat, Daniel, Collins, V Peter, Eberhart, Charles, Figarella‐Branger, Dominique, Fuller, Gregory N, Giangaspero, Felice, Giannini, Caterina, Hawkins, Cynthia, Kleihues, Paul, Korshunov, Andrey, Kros, Johan M, Lopes, M Beatriz, Ng, Ho‐Keung, Ohgaki, Hiroko, Paulus, Werner, Pietsch, Torsten, Rosenblum, Marc, Rushing, Elisabeth, Soylemezoglu, Figen, Wiestler, Otmar, and Wesseling, Pieter

Subjects
Biomedical and Clinical Sciences, Clinical Sciences, Brain Disorders, Rare Diseases, Brain Cancer, Neurosciences, Cancer, Humans, Molecular Diagnostic Techniques, Nervous System Neoplasms, Severity of Illness Index, Astrocytoma, atypical teratoid rhabdoid tumor, brain tumors, classification, glioblastoma, glioma, grading, medulloblastoma, oligodendroglioma, World Health Organization, International Society Of Neuropathology--Haarlem, Neurology & Neurosurgery, Clinical sciences
Abstract

Major discoveries in the biology of nervous system tumors have raised the question of how non-histological data such as molecular information can be incorporated into the next World Health Organization (WHO) classification of central nervous system tumors. To address this question, a meeting of neuropathologists with expertise in molecular diagnosis was held in Haarlem, the Netherlands, under the sponsorship of the International Society of Neuropathology (ISN). Prior to the meeting, participants solicited input from clinical colleagues in diverse neuro-oncological specialties. The present "white paper" catalogs the recommendations of the meeting, at which a consensus was reached that incorporation of molecular information into the next WHO classification should follow a set of provided "ISN-Haarlem" guidelines. Salient recommendations include that (i) diagnostic entities should be defined as narrowly as possible to optimize interobserver reproducibility, clinicopathological predictions and therapeutic planning; (ii) diagnoses should be "layered" with histologic classification, WHO grade and molecular information listed below an "integrated diagnosis"; (iii) determinations should be made for each tumor entity as to whether molecular information is required, suggested or not needed for its definition; (iv) some pediatric entities should be separated from their adult counterparts; (v) input for guiding decisions regarding tumor classification should be solicited from experts in complementary disciplines of neuro-oncology; and (iv) entity-specific molecular testing and reporting formats should be followed in diagnostic reports. It is hoped that these guidelines will facilitate the forthcoming update of the fourth edition of the WHO classification of central nervous system tumors.

Published
2014

7. Genome Sequencing of SHH Medulloblastoma Predicts Genotype-Related Response to Smoothened Inhibition

Author

Kool, Marcel, Jones, David TW, Jäger, Natalie, Northcott, Paul A, Pugh, Trevor J, Hovestadt, Volker, Piro, Rosario M, Esparza, L Adriana, Markant, Shirley L, Remke, Marc, Milde, Till, Bourdeaut, Franck, Ryzhova, Marina, Sturm, Dominik, Pfaff, Elke, Stark, Sebastian, Hutter, Sonja, Şeker-Cin, Huriye, Johann, Pascal, Bender, Sebastian, Schmidt, Christin, Rausch, Tobias, Shih, David, Reimand, Jüri, Sieber, Laura, Wittmann, Andrea, Linke, Linda, Witt, Hendrik, Weber, Ursula D, Zapatka, Marc, König, Rainer, Beroukhim, Rameen, Bergthold, Guillaume, van Sluis, Peter, Volckmann, Richard, Koster, Jan, Versteeg, Rogier, Schmidt, Sabine, Wolf, Stephan, Lawerenz, Chris, Bartholomae, Cynthia C, von Kalle, Christof, Unterberg, Andreas, Herold-Mende, Christel, Hofer, Silvia, Kulozik, Andreas E, von Deimling, Andreas, Scheurlen, Wolfram, Felsberg, Jörg, Reifenberger, Guido, Hasselblatt, Martin, Crawford, John R, Grant, Gerald A, Jabado, Nada, Perry, Arie, Cowdrey, Cynthia, Croul, Sydney, Zadeh, Gelareh, Korbel, Jan O, Doz, Francois, Delattre, Olivier, Bader, Gary D, McCabe, Martin G, Collins, V Peter, Kieran, Mark W, Cho, Yoon-Jae, Pomeroy, Scott L, Witt, Olaf, Brors, Benedikt, Taylor, Michael D, Schüller, Ulrich, Korshunov, Andrey, Eils, Roland, Wechsler-Reya, Robert J, Lichter, Peter, Pfister, Stefan M, and Project, on behalf of the ICGC PedBrain Tumor

Subjects
Biological Sciences, Biomedical and Clinical Sciences, Clinical Sciences, Neurosciences, Pediatric Research Initiative, Genetics, Rare Diseases, Cancer, Pediatric, Brain Cancer, Pediatric Cancer, Brain Disorders, Adolescent, Adult, Animals, Base Sequence, Biphenyl Compounds, Cerebellar Neoplasms, Child, Child, Preschool, DEAD-box RNA Helicases, DNA Copy Number Variations, Drug Resistance, Neoplasm, Female, Gene Expression Profiling, Hedgehog Proteins, High-Throughput Nucleotide Sequencing, Humans, Infant, Kruppel-Like Transcription Factors, Male, Medulloblastoma, Mice, Mice, Inbred NOD, Mice, SCID, Molecular Sequence Data, N-Myc Proto-Oncogene Protein, Neoplasm Transplantation, Nuclear Proteins, Oncogene Proteins, Patched Receptors, Patched-1 Receptor, Phosphatidylinositol 3-Kinases, Promoter Regions, Genetic, Proto-Oncogene Proteins c-akt, Pyridines, Receptors, Cell Surface, Receptors, G-Protein-Coupled, Repressor Proteins, Signal Transduction, Smoothened Receptor, Telomerase, Tumor Suppressor Protein p53, Young Adult, Zinc Finger Protein Gli2, ICGC PedBrain Tumor Project, Oncology and Carcinogenesis, Oncology & Carcinogenesis, Biochemistry and cell biology, Oncology and carcinogenesis
Abstract

Smoothened (SMO) inhibitors recently entered clinical trials for sonic-hedgehog-driven medulloblastoma (SHH-MB). Clinical response is highly variable. To understand the mechanism(s) of primary resistance and identify pathways cooperating with aberrant SHH signaling, we sequenced and profiled a large cohort of SHH-MBs (n = 133). SHH pathway mutations involved PTCH1 (across all age groups), SUFU (infants, including germline), and SMO (adults). Children >3 years old harbored an excess of downstream MYCN and GLI2 amplifications and frequent TP53 mutations, often in the germline, all of which were rare in infants and adults. Functional assays in different SHH-MB xenograft models demonstrated that SHH-MBs harboring a PTCH1 mutation were responsive to SMO inhibition, whereas tumors harboring an SUFU mutation or MYCN amplification were primarily resistant.

Published
2014

8. Clonal selection drives genetic divergence of metastatic medulloblastoma.

Author

Wu, Xiaochong, Northcott, Paul A, Dubuc, Adrian, Dupuy, Adam J, Shih, David JH, Witt, Hendrik, Croul, Sidney, Bouffet, Eric, Fults, Daniel W, Eberhart, Charles G, Garzia, Livia, Van Meter, Timothy, Zagzag, David, Jabado, Nada, Schwartzentruber, Jeremy, Majewski, Jacek, Scheetz, Todd E, Pfister, Stefan M, Korshunov, Andrey, Li, Xiao-Nan, Scherer, Stephen W, Cho, Yoon-Jae, Akagi, Keiko, MacDonald, Tobey J, Koster, Jan, McCabe, Martin G, Sarver, Aaron L, Collins, V Peter, Weiss, William A, Largaespada, David A, Collier, Lara S, and Taylor, Michael D

Subjects
Animals, Humans, Mice, Medulloblastoma, Neoplasm Metastasis, Li-Fraumeni Syndrome, Disease Models, Animal, DNA Transposable Elements, Survival Rate, Mutagenesis, Insertional, DNA Methylation, CpG Islands, Germ-Line Mutation, Genes, p53, Clonal Evolution, Disease Models, Animal, Genes, p53, Mutagenesis, Insertional, General Science & Technology
Abstract

Medulloblastoma, the most common malignant paediatric brain tumour, arises in the cerebellum and disseminates through the cerebrospinal fluid in the leptomeningeal space to coat the brain and spinal cord. Dissemination, a marker of poor prognosis, is found in up to 40% of children at diagnosis and in most children at the time of recurrence. Affected children therefore are treated with radiation to the entire developing brain and spinal cord, followed by high-dose chemotherapy, with the ensuing deleterious effects on the developing nervous system. The mechanisms of dissemination through the cerebrospinal fluid are poorly studied, and medulloblastoma metastases have been assumed to be biologically similar to the primary tumour. Here we show that in both mouse and human medulloblastoma, the metastases from an individual are extremely similar to each other but are divergent from the matched primary tumour. Clonal genetic events in the metastases can be demonstrated in a restricted subclone of the primary tumour, suggesting that only rare cells within the primary tumour have the ability to metastasize. Failure to account for the bicompartmental nature of metastatic medulloblastoma could be a major barrier to the development of effective targeted therapies.

Published
2012

9. DNA methylation-based classification and grading system for meningioma: a multicentre, retrospective analysis

Author

Sahm, Felix, Schrimpf, Daniel, Stichel, Damian, Jones, David T W, Hielscher, Thomas, Schefzyk, Sebastian, Okonechnikov, Konstantin, Koelsche, Christian, Reuss, David E, Capper, David, Sturm, Dominik, Wirsching, Hans-Georg, Berghoff, Anna Sophie, Baumgarten, Peter, Kratz, Annekathrin, Huang, Kristin, Wefers, Annika K, Hovestadt, Volker, Sill, Martin, Ellis, Hayley P, Kurian, Kathreena M, Okuducu, Ali Fuat, Jungk, Christine, Drueschler, Katharina, Schick, Matthias, Bewerunge-Hudler, Melanie, Mawrin, Christian, Seiz-Rosenhagen, Marcel, Ketter, Ralf, Simon, Matthias, Westphal, Manfred, Lamszus, Katrin, Becker, Albert, Koch, Arend, Schittenhelm, Jens, Rushing, Elisabeth J, Collins, V Peter, Brehmer, Stefanie, Chavez, Lukas, Platten, Michael, Hänggi, Daniel, Unterberg, Andreas, Paulus, Werner, Wick, Wolfgang, Pfister, Stefan M, Mittelbronn, Michel, Preusser, Matthias, Herold-Mende, Christel, Weller, Michael, and von Deimling, Andreas

Published
2017
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11. Supplementary Data from High-Resolution Array-Based Comparative Genomic Hybridization of Bladder Cancers Identifies Mouse Double Minute 4 (MDM4) as an Amplification Target Exclusive of MDM2 and TP53

Author

Veerakumarasivam, Abhi, primary, Scott, Helen E., primary, Chin, Suet-Feung, primary, Warren, Anne, primary, Wallard, Matthew J., primary, Grimmer, Donna, primary, Ichimura, Koichi, primary, Caldas, Carlos, primary, Collins, V. Peter, primary, Neal, David E., primary, and Kelly, John D., primary

Published
2023
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12. Supplementary Data from Genetic Aberrations Leading to MAPK Pathway Activation Mediate Oncogene-Induced Senescence in Sporadic Pilocytic Astrocytomas

Author

Jacob, Karine, primary, Quang-Khuong, Dongh-Anh, primary, Jones, David T.W., primary, Witt, Hendrik, primary, Lambert, Sally, primary, Albrecht, Steffen, primary, Witt, Olaf, primary, Vezina, Catherine, primary, Shirinian, Margret, primary, Faury, Damien, primary, Garami, Miklos, primary, Hauser, Peter, primary, Klekner, Almos, primary, Bognar, Laszlo, primary, Farmer, Jean-Pierre, primary, Montes, Jose-Luis, primary, Atkinson, Jeffrey, primary, Hawkins, Cynthia, primary, Korshunov, Andrey, primary, Collins, V. Peter, primary, Pfister, Stefan M., primary, Tabori, Uri, primary, and Jabado, Nada, primary

Published
2023
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13. Supplementary Table H from Improved grading and survival prediction of human astrocytic brain tumors by artificial neural network analysis of gene expression microarray data

Author

Petalidis, Lawrence P., primary, Oulas, Anastasis, primary, Backlund, Magnus, primary, Wayland, Matthew T., primary, Liu, Lu, primary, Plant, Karen, primary, Happerfield, Lisa, primary, Freeman, Tom C., primary, Poirazi, Panayiota, primary, and Collins, V. Peter, primary

Published
2023
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14. Data from High-Resolution Array-Based Comparative Genomic Hybridization of Bladder Cancers Identifies Mouse Double Minute 4 (MDM4) as an Amplification Target Exclusive of MDM2 and TP53

Author

Veerakumarasivam, Abhi, primary, Scott, Helen E., primary, Chin, Suet-Feung, primary, Warren, Anne, primary, Wallard, Matthew J., primary, Grimmer, Donna, primary, Ichimura, Koichi, primary, Caldas, Carlos, primary, Collins, V. Peter, primary, Neal, David E., primary, and Kelly, John D., primary

Published
2023
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15. Supplementary Information from Improved grading and survival prediction of human astrocytic brain tumors by artificial neural network analysis of gene expression microarray data

Author

Petalidis, Lawrence P., primary, Oulas, Anastasis, primary, Backlund, Magnus, primary, Wayland, Matthew T., primary, Liu, Lu, primary, Plant, Karen, primary, Happerfield, Lisa, primary, Freeman, Tom C., primary, Poirazi, Panayiota, primary, and Collins, V. Peter, primary

Published
2023
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16. Supplementary Table F from Improved grading and survival prediction of human astrocytic brain tumors by artificial neural network analysis of gene expression microarray data

Author

Petalidis, Lawrence P., primary, Oulas, Anastasis, primary, Backlund, Magnus, primary, Wayland, Matthew T., primary, Liu, Lu, primary, Plant, Karen, primary, Happerfield, Lisa, primary, Freeman, Tom C., primary, Poirazi, Panayiota, primary, and Collins, V. Peter, primary

Published
2023
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17. Supplementary Table G from Improved grading and survival prediction of human astrocytic brain tumors by artificial neural network analysis of gene expression microarray data

Author

Petalidis, Lawrence P., primary, Oulas, Anastasis, primary, Backlund, Magnus, primary, Wayland, Matthew T., primary, Liu, Lu, primary, Plant, Karen, primary, Happerfield, Lisa, primary, Freeman, Tom C., primary, Poirazi, Panayiota, primary, and Collins, V. Peter, primary

Published
2023
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23. An integrated genomic analysis of anaplastic meningioma identifies prognostic molecular signatures

Author

Collord, Grace, Tarpey, Patrick, Kurbatova, Natalja, Martincorena, Inigo, Moran, Sebastian, Castro, Manuel, Nagy, Tibor, Bignell, Graham, Maura, Francesco, Young, Matthew D., Berna, Jorge, Tubio, Jose M. C., McMurran, Chris E., Young, Adam M. H., Sanders, Mathijs, Noorani, Imran, Price, Stephen J., Watts, Colin, Leipnitz, Elke, Kirsch, Matthias, Schackert, Gabriele, Pearson, Danita, Devadass, Abel, Ram, Zvi, Collins, V. Peter, Allinson, Kieren, Jenkinson, Michael D., Zakaria, Rasheed, Syed, Khaja, Hanemann, C. Oliver, Dunn, Jemma, McDermott, Michael W., Kirollos, Ramez W., Vassiliou, George S., Esteller, Manel, Behjati, Sam, Brazma, Alvis, Santarius, Thomas, and McDermott, Ultan

Published
2018
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25. Molecular profiling of long-term survivors identifies a subgroup of glioblastoma characterized by chromosome 19/20 co-gain

Author

Geisenberger, Christoph, Mock, Andreas, Warta, Rolf, Rapp, Carmen, Schwager, Christian, Korshunov, Andrey, Nied, Ann-Katrin, Capper, David, Brors, Benedikt, Jungk, Christine, Jones, David, Collins, V. Peter, Ichimura, Koichi, Bäcklund, L. Magnus, Schnabel, Elena, Mittelbron, Michel, Lahrmann, Bernd, Zheng, Siyuan, Verhaak, Roel G. W., Grabe, Niels, Pfister, Stefan M., Hartmann, Christian, von Deimling, Andreas, Debus, Jürgen, Unterberg, Andreas, Abdollahi, Amir, and Herold-Mende, Christel

Published
2015
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26. Hotspot Mutations in H3F3A and IDH1 Define Distinct Epigenetic and Biological Subgroups of Glioblastoma

Author

Sturm, Dominik, Witt, Hendrik, Hovestadt, Volker, Khuong-Quang, Dong-Anh, Jones, David T.W., Konermann, Carolin, Pfaff, Elke, Tönjes, Martje, Sill, Martin, Bender, Sebastian, Kool, Marcel, Zapatka, Marc, Becker, Natalia, Zucknick, Manuela, Hielscher, Thomas, Liu, Xiao-Yang, Fontebasso, Adam M., Ryzhova, Marina, Albrecht, Steffen, Jacob, Karine, Wolter, Marietta, Ebinger, Martin, Schuhmann, Martin U., van Meter, Timothy, Frühwald, Michael C., Hauch, Holger, Pekrun, Arnulf, Radlwimmer, Bernhard, Niehues, Tim, von Komorowski, Gregor, Dürken, Matthias, Kulozik, Andreas E., Madden, Jenny, Donson, Andrew, Foreman, Nicholas K., Drissi, Rachid, Fouladi, Maryam, Scheurlen, Wolfram, von Deimling, Andreas, Monoranu, Camelia, Roggendorf, Wolfgang, Herold-Mende, Christel, Unterberg, Andreas, Kramm, Christof M., Felsberg, Jörg, Hartmann, Christian, Wiestler, Benedikt, Wick, Wolfgang, Milde, Till, Witt, Olaf, Lindroth, Anders M., Schwartzentruber, Jeremy, Faury, Damien, Fleming, Adam, Zakrzewska, Magdalena, Liberski, Pawel P., Zakrzewski, Krzysztof, Hauser, Peter, Garami, Miklos, Klekner, Almos, Bognar, Laszlo, Morrissy, Sorana, Cavalli, Florence, Taylor, Michael D., van Sluis, Peter, Koster, Jan, Versteeg, Rogier, Volckmann, Richard, Mikkelsen, Tom, Aldape, Kenneth, Reifenberger, Guido, Collins, V. Peter, Majewski, Jacek, Korshunov, Andrey, Lichter, Peter, Plass, Christoph, Jabado, Nada, and Pfister, Stefan M.

Published
2012
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28. AKT1E17K mutations cluster with meningothelial and transitional meningiomas and can be detected by SFRP1 immunohistochemistry

Author

Sahm, Felix, Bissel, Juliane, Koelsche, Christian, Schweizer, Leonille, Capper, David, Reuss, David, Böhmer, Katja, Lass, Ulrike, Göck, Tanja, Kalis, Katrin, Meyer, Jochen, Habel, Antje, Brehmer, Stefanie, Mittelbronn, Michel, Jones, David T. W., Schittenhelm, Jens, Urbschat, Steffi, Ketter, Ralf, Heim, Stephanie, Mawrin, Christian, Hainfellner, Johannes A., Berghoff, Anna-Sophie, Preusser, Matthias, Becker, Albert, Herold-Mende, Christel, Unterberg, Andreas, Hartmann, Christian, Kickingereder, Philipp, Collins, V. Peter, Pfister, Stefan M., and von Deimling, Andreas

Published
2013
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29. Frequent Amplification of a chr19q13.41 MicroRNA Polycistron in Aggressive Primitive Neuroectodermal Brain Tumors

Author

Li, Meihua, Lee, Kyle F., Lu, Yuntao, Clarke, Ian, Shih, David, Eberhart, Charles, Collins, V. Peter, Van Meter, Tim, Picard, Daniel, Zhou, Limei, Boutros, Paul C., Modena, Piergiorgio, Liang, Muh-Lii, Scherer, Steve W., Bouffet, Eric, Rutka, James T., Pomeroy, Scott L., Lau, Ching C., Taylor, Michael D., Gajjar, Amar, Dirks, Peter B., Hawkins, Cynthia E., and Huang, Annie

Published
2009
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36. Secretory meningiomas are defined by combined KLF4 K409Q and TRAF7 mutations

Author

Reuss, David E., Piro, Rosario M., Jones, David T. W., Simon, Matthias, Ketter, Ralf, Kool, Marcel, Becker, Albert, Sahm, Felix, Pusch, Stefan, Meyer, Jochen, Hagenlocher, Christian, Schweizer, Leonille, Capper, David, Kickingereder, Phillipp, Mucha, Jana, Koelsche, Christian, Jäger, Natalie, Santarius, Thomas, Tarpey, Patrick S., Stephens, Philip J., Andrew Futreal, P., Wellenreuther, Ruth, Kraus, Jürgen, Lenartz, Doris, Herold-Mende, Christel, Hartmann, Christian, Mawrin, Christian, Giese, Nathalia, Eils, Roland, Collins, V. Peter, König, Rainer, Wiestler, Otmar D., Pfister, Stefan M., and von Deimling, Andreas

Published
2013
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37. LIN28A immunoreactivity is a potent diagnostic marker of embryonal tumor with multilayered rosettes (ETMR)

Author

Korshunov, Andrey, Ryzhova, Marina, Jones, David T. W., Northcott, Paul A., van Sluis, Peter, Volckmann, Richard, Koster, Jan, Versteeg, Rogier, Cowdrey, Cynthia, Perry, Arie, Picard, Daniel, Rosenblum, Marc, Giangaspero, Felice, Aronica, Eleonora, Schüller, Ulrich, Hasselblatt, Martin, Collins, V. Peter, von Deimling, Andreas, Lichter, Peter, Huang, Annie, Pfister, Stefan M., and Kool, Marcel

Published
2012
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39. Molecular subgroups of medulloblastoma: an international meta-analysis of transcriptome, genetic aberrations, and clinical data of WNT, SHH, Group 3, and Group 4 medulloblastomas

Author

Kool, Marcel, Korshunov, Andrey, Remke, Marc, Jones, David T. W., Schlanstein, Maria, Northcott, Paul A., Cho, Yoon-Jae, Koster, Jan, Schouten-van Meeteren, Antoinette, van Vuurden, Dannis, Clifford, Steven C., Pietsch, Torsten, von Bueren, Andre O., Rutkowski, Stefan, McCabe, Martin, Collins, V. Peter, Bäcklund, Magnus L., Haberler, Christine, Bourdeaut, Franck, Delattre, Olivier, Doz, Francois, Ellison, David W., Gilbertson, Richard J., Pomeroy, Scott L., Taylor, Michael D., Lichter, Peter, and Pfister, Stefan M.

Published
2012
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40. Driver mutations in histone H3.3 and chromatin remodelling genes in paediatric glioblastoma

Author

Schwartzentruber, Jeremy, Korshunov, Andrey, Liu, Xiao-Yang, Jones, David T.W., Pfaff, Elke, Jacob, Karine, Sturm, Dominik, Fontebasso, Adam M., Quang, Dong-Anh Khuong, Tonjes, Martje, Hovestadt, Volker, Albrecht, Steffen, Kool, Marcel, Nantel, Andre, Konermann, Carolin, Lindroth, Anders, Jager, Natalie, Rausch, Tobias, Ryzhova, Marina, Korbel, Jan O., Hielscher, Thomas, Hauser, Peter, Garami, Miklos, Klekner, Almos, Bognar, Laszlo, Ebinger, Martin, Schuhmann, Martin U., Scheurlen, Wolfram, Pekrun, Arnulf, Fruhwald, Michael C., Roggendorf, Wolfgang, Kramm, Christoph, Durken, Matthias, Atkinson, Jeffrey, Lepage, Pierre, Montpetit, Alexandre, Zakrzewska, Magdalena, Zakrzewski, Krzystof, Liberski, Pawel P., Dong, Zhifeng, Siegel, Peter, Kulozik, Andreas E., Zapatka, Marc, Guha, Abhijit, Malkin, David, Felsberg, Jorg, Reifenberger, Guido, von Deimling, Andreas, Ichimura, Koichi, Collins, V. Peter, Witt, Hendrik, Milde, Till, Witt, Olaf, Zhang, Cindy, Castelo-Branco, Pedro, Lichter, Peter, Faury, Damien, Tabori, Uri, Plass, Christoph, Majewski, Jacek, Pfister, Stefan M., and Jabado, Nada

Subjects
Gene mutations -- Research, DNA -- Physiological aspects -- Research, Tumor proteins -- Physiological aspects -- Research, Glioblastoma multiforme -- Genetic aspects -- Research, Environmental issues, Science and technology, Zoology and wildlife conservation
Abstract

Glioblastoma multiforme (GBM) is a lethal brain tumour in adults and children. However, DNA copy number and gene expression signatures indicate differences between adult and paediatric cases (1-4). To explore the genetic events underlying this distinction, we sequenced the exomes of 48 paediatric GBM samples. Somatic mutations in the H3.3-ATRX-DAXX chromatin remodelling pathway were identified in 44% of tumours (21/48). Recurrent mutations in H3F3A, which encodes the replication-independent histone 3 variant H3.3, were observed in 31% of tumours, and led to amino acid substitutions at two critical positions within the histone tail (K27M, G34R/G34V) involved in key regulatory post-translational modifications. Mutations in ATRX(α-thalassaemia/mental retardation syndrome X-linked) (5) and DAXX (death-domain associated protein), encoding two subunits of a chromatin remodelling complex required for H3.3 incorporation at pericentric heterochromatin and telomeres (6,7), were identified in 31% of samples overall, and in 100% of tumours harbouring a G34R or G34V H3.3 mutation. Somatic TP53 mutations were identified in 54% of all cases, and in 86% of samples with H3F3A and/or ATRX mutations. Screening of a large cohort of gliomas of various grades and histologies (n = 784) showed H3F3A mutations to be specific to GBM and highly prevalent in children and young adults. Furthermore, the presence of H3F3A/ATRX-DAXX/TP53 mutations was strongly associated with alternative lengthening of telomeres and specific gene expression profiles. This is, to our knowledge, the first report to highlight recurrent mutations in a regulatory histone in humans, and our data suggest that defects of the chromatin architecture underlie paediatric and young adult GBM pathogenesis., Brain tumours are currently the leading cause of cancer-related mortality and morbidity in children. Glioblastoma multiforme (GBM) is a highly aggressive brain tumour and the first cancer to be comprehensively [...]

Published
2012
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42. Oncogenic FAM131B–BRAF fusion resulting from 7q34 deletion comprises an alternative mechanism of MAPK pathway activation in pilocytic astrocytoma

Author

Cin, Huriye, Meyer, Claus, Herr, Ricarda, Janzarik, Wibke G., Lambert, Sally, Jones, David T. W., Jacob, Karine, Benner, Axel, Witt, Hendrik, Remke, Marc, Bender, Sebastian, Falkenstein, Fabian, Van Anh, Ton Nu, Olbrich, Heike, von Deimling, Andreas, Pekrun, Arnulf, Kulozik, Andreas E., Gnekow, Astrid, Scheurlen, Wolfram, Witt, Olaf, Omran, Heymut, Jabado, Nada, Collins, V. Peter, Brummer, Tilman, Marschalek, Rolf, Lichter, Peter, Korshunov, Andrey, and Pfister, Stefan M.

Published
2011
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50. Contributors

Author

Adler, John R., primary, Aglio, Linda S., additional, Akalan, Nejat, additional, Albayrak, Serdar Baki, additional, Al-Mefty, Ossama, additional, Alvernia, Jorge E., additional, Baleriaux, Danielle, additional, Baltacioğlu, Feyyaz, additional, Basiouni, Hiriam, additional, Belirgen, Muhittin, additional, Bello, Jacqueline A., additional, Bhaganagare, Amaresh S., additional, Black, Peter M., additional, Börcek, Alp Özgün, additional, Borchers, John, additional, Brada, Michael, additional, Brotchi, Jacques, additional, Bruneau, Michael, additional, Calvocoressi, Lisa, additional, Carrabba, Giorgio, additional, Carroll, Rona S., additional, Claus, Elizabeth B., additional, Collins, V. Peter, additional, Coppens, Jeroen R., additional, Couldwell, William T., additional, Couser, Chris, additional, de Paiva Neto, Manoel A., additional, Desai, Ketan I., additional, Dinçer, Alp, additional, Doglietto, Francesco, additional, Dusick, Joshua R., additional, Erzen, Canan, additional, Fahlbusch, Rudolf, additional, Farinhas, Joaquim M., additional, Fatemi, Nasrin, additional, Fraifeld, Shifra, additional, Gentili, Fred, additional, Gerganov, Venelin M., additional, Goel, Atul, additional, Golby, Alexandra J., additional, Gold, Menachem M., additional, Gormley, William B., additional, Governale, Lance S., additional, Guha, Abhijit, additional, Hara, Wendy, additional, Hasegawa, Toshinori, additional, Hassler, Werner, additional, Hoang, Stanley, additional, Hofmann, Bernd M., additional, Holzemer, Liz L., additional, Hornyak, Mark, additional, Jayne, John A., additional, Kalamarides, Michel, additional, Kano, Hideyuki, additional, Kansu, Tulay, additional, Kawase, Takeshi, additional, Kaya, Dilaver, additional, Kaye, Andrew H., additional, Kelly, Daniel F., additional, Kikinis, Ron, additional, Kiliç, Türker, additional, King, James A.J., additional, Kohan, Saeed, additional, Kondziolka, Douglas, additional, Konukoglu, Ender, additional, Konya, Deniz, additional, Krayenbühl, Niklaus, additional, Kubo, Osami, additional, Laws, Edward R., additional, Li, Gordon, additional, Loeffler, Jay S., additional, Lunsford, L. Dade, additional, Malkasian, Dennis, additional, Martins, Carolina, additional, Mathiesen, Tiit, additional, Minniti, Giuseppe, additional, Mukhopadhyay, Debabrata, additional, Niranjan, Ajay, additional, Norden, Andrew D., additional, Ono, Y., additional, Özduman, Koray, additional, Özek, M. Memet, additional, Özgen, Serdar, additional, Özgen, Tuncalp, additional, Pamir, M. Necmettin, additional, Patil, Chirag G., additional, Peker, Selçuk, additional, Pham, Annette M., additional, Piepmeier, Joseph M., additional, Pohl, Killian M., additional, Radovanovic, Ivan, additional, Ramakrishna, Naren Raj, additional, Rhoton, Albert L., additional, Rosenthal, Guy, additional, Rutka, James T., additional, Rutka, John A., additional, Sadetzki, Siegal, additional, Sakamoto, Gordon T., additional, Sakata, Katsumi, additional, Samii, Madjid, additional, Sav, Aydin, additional, Scheithauer, Bernd, additional, Schick, Uta, additional, Schramm, Johannes, additional, Schweder, Patrick, additional, Seifert, Volker, additional, Seker, Askin, additional, Shifteh, Keivan, additional, Shih, Helen A., additional, Shoshan, Yigal, additional, Simon, Matthias, additional, Simons, Robert L., additional, Sindou, Marc P., additional, Spektor, Sergey, additional, Takakura, K., additional, Tariq, Farzana, additional, Teramoto, A., additional, Umansky, Felix, additional, Us, Onder, additional, Ware, Marcus L., additional, Weber, Damien C., additional, Wen, Patrick Y., additional, Wollmann, Guido, additional, Yamamoto, Isao, additional, Yoshida, Jun, additional, and Zauberman, Jacob, additional

Published
2010
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