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1. Moving towards Inclusive Education: Secondary School Teacher Attitudes towards Universal Design for Learning in Australia

Author

Chen, Hongyu, Evans, David, and Luu, Betty

Abstract

Achieving Sustainable Development Goal 4 is underpinned by the provision of quality inclusive education for all young persons, including persons with disabilities. The universal design for learning (UDL) framework provides the basis for establishing an inclusive pedagogical learning environment in classrooms. However, implementing such an inclusive pedagogical framework continues to be profoundly challenging across all countries, including Australia. Teacher attitude is the most important construct in efforts to create inclusive educational contexts. The aim of this study was to examine secondary school teachers' attitudes towards the UDL framework in Australia. One hundred and twenty mainstream secondary classroom teachers in Sydney completed an online survey. The mean values and standard deviations of a self-designed UDL framework were calculated to examine teacher attitudes. Correlations and multiple regressions were conducted to verify the relationship between teachers' attitudes and their background variables. The main results indicated that Australian secondary school teacher attitudes towards the UDL framework were generally positive, although they still had some practical concerns, such as having inflexible ideas about how to provide instructions. The findings provide useful insights for developing professional teacher training to promote inclusive education, where the UDL framework is a lens for interpreting inclusive education.

Published
2023
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2. Failure of human rhombic lip differentiation underlies medulloblastoma formation

Author

Hendrikse, Liam D, Haldipur, Parthiv, Saulnier, Olivier, Millman, Jake, Sjoboen, Alexandria H, Erickson, Anders W, Ong, Winnie, Gordon, Victor, Coudière-Morrison, Ludivine, Mercier, Audrey L, Shokouhian, Mohammad, Suárez, Raúl A, Ly, Michelle, Borlase, Stephanie, Scott, David S, Vladoiu, Maria C, Farooq, Hamza, Sirbu, Olga, Nakashima, Takuma, Nambu, Shohei, Funakoshi, Yusuke, Bahcheli, Alec, Diaz-Mejia, J Javier, Golser, Joseph, Bach, Kathleen, Phuong-Bao, Tram, Skowron, Patryk, Wang, Evan Y, Kumar, Sachin A, Balin, Polina, Visvanathan, Abhirami, Lee, John JY, Ayoub, Ramy, Chen, Xin, Chen, Xiaodi, Mungall, Karen L, Luu, Betty, Bérubé, Pierre, Wang, Yu C, Pfister, Stefan M, Kim, Seung-Ki, Delattre, Olivier, Bourdeaut, Franck, Doz, François, Masliah-Planchon, Julien, Grajkowska, Wieslawa A, Loukides, James, Dirks, Peter, Fèvre-Montange, Michelle, Jouvet, Anne, French, Pim J, Kros, Johan M, Zitterbart, Karel, Bailey, Swneke D, Eberhart, Charles G, Rao, Amulya AN, Giannini, Caterina, Olson, James M, Garami, Miklós, Hauser, Peter, Phillips, Joanna J, Ra, Young S, de Torres, Carmen, Mora, Jaume, Li, Kay KW, Ng, Ho-Keung, Poon, Wai S, Pollack, Ian F, López-Aguilar, Enrique, Gillespie, G Yancey, Van Meter, Timothy E, Shofuda, Tomoko, Vibhakar, Rajeev, Thompson, Reid C, Cooper, Michael K, Rubin, Joshua B, Kumabe, Toshihiro, Jung, Shin, Lach, Boleslaw, Iolascon, Achille, Ferrucci, Veronica, de Antonellis, Pasqualino, Zollo, Massimo, Cinalli, Giuseppe, Robinson, Shenandoah, Stearns, Duncan S, Van Meir, Erwin G, Porrati, Paola, Finocchiaro, Gaetano, Massimino, Maura, Carlotti, Carlos G, Faria, Claudia C, Roussel, Martine F, Boop, Frederick, Chan, Jennifer A, Aldinger, Kimberly A, Razavi, Ferechte, Silvestri, Evelina, McLendon, Roger E, and Thompson, Eric M

Subjects
Stem Cell Research, Brain Disorders, Neurosciences, Rare Diseases, Stem Cell Research - Nonembryonic - Non-Human, Aetiology, 1.1 Normal biological development and functioning, Underpinning research, 2.1 Biological and endogenous factors, Cell Differentiation, Cell Lineage, Cerebellar Neoplasms, Cerebellum, Core Binding Factor alpha Subunits, Hedgehog Proteins, Histone Demethylases, Humans, Ki-67 Antigen, Medulloblastoma, Metencephalon, Muscle Proteins, Mutation, Otx Transcription Factors, Repressor Proteins, T-Box Domain Proteins, Transcription Factors, General Science & Technology
Abstract

Medulloblastoma (MB) comprises a group of heterogeneous paediatric embryonal neoplasms of the hindbrain with strong links to early development of the hindbrain1-4. Mutations that activate Sonic hedgehog signalling lead to Sonic hedgehog MB in the upper rhombic lip (RL) granule cell lineage5-8. By contrast, mutations that activate WNT signalling lead to WNT MB in the lower RL9,10. However, little is known about the more commonly occurring group 4 (G4) MB, which is thought to arise in the unipolar brush cell lineage3,4. Here we demonstrate that somatic mutations that cause G4 MB converge on the core binding factor alpha (CBFA) complex and mutually exclusive alterations that affect CBFA2T2, CBFA2T3, PRDM6, UTX and OTX2. CBFA2T2 is expressed early in the progenitor cells of the cerebellar RL subventricular zone in Homo sapiens, and G4 MB transcriptionally resembles these progenitors but are stalled in developmental time. Knockdown of OTX2 in model systems relieves this differentiation blockade, which allows MB cells to spontaneously proceed along normal developmental differentiation trajectories. The specific nature of the split human RL, which is destined to generate most of the neurons in the human brain, and its high level of susceptible EOMES+KI67+ unipolar brush cell progenitor cells probably predisposes our species to the development of G4 MB.

Published
2022

3. The transcriptional landscape of Shh medulloblastoma.

Author

Skowron, Patryk, Farooq, Hamza, Cavalli, Florence MG, Morrissy, A Sorana, Ly, Michelle, Hendrikse, Liam D, Wang, Evan Y, Djambazian, Haig, Zhu, Helen, Mungall, Karen L, Trinh, Quang M, Zheng, Tina, Dai, Shizhong, Stucklin, Ana S Guerreiro, Vladoiu, Maria C, Fong, Vernon, Holgado, Borja L, Nor, Carolina, Wu, Xiaochong, Abd-Rabbo, Diala, Bérubé, Pierre, Wang, Yu Chang, Luu, Betty, Suarez, Raul A, Rastan, Avesta, Gillmor, Aaron H, Lee, John JY, Zhang, Xiao Yun, Daniels, Craig, Dirks, Peter, Malkin, David, Bouffet, Eric, Tabori, Uri, Loukides, James, Doz, François P, Bourdeaut, Franck, Delattre, Olivier O, Masliah-Planchon, Julien, Ayrault, Olivier, Kim, Seung-Ki, Meyronet, David, Grajkowska, Wieslawa A, Carlotti, Carlos G, de Torres, Carmen, Mora, Jaume, Eberhart, Charles G, Van Meir, Erwin G, Kumabe, Toshihiro, French, Pim J, Kros, Johan M, Jabado, Nada, Lach, Boleslaw, Pollack, Ian F, Hamilton, Ronald L, Rao, Amulya A Nageswara, Giannini, Caterina, Olson, James M, Bognár, László, Klekner, Almos, Zitterbart, Karel, Phillips, Joanna J, Thompson, Reid C, Cooper, Michael K, Rubin, Joshua B, Liau, Linda M, Garami, Miklós, Hauser, Peter, Li, Kay Ka Wai, Ng, Ho-Keung, Poon, Wai Sang, Yancey Gillespie, G, Chan, Jennifer A, Jung, Shin, McLendon, Roger E, Thompson, Eric M, Zagzag, David, Vibhakar, Rajeev, Ra, Young Shin, Garre, Maria Luisa, Schüller, Ulrich, Shofuda, Tomoko, Faria, Claudia C, López-Aguilar, Enrique, Zadeh, Gelareh, Hui, Chi-Chung, Ramaswamy, Vijay, Bailey, Swneke D, Jones, Steven J, Mungall, Andrew J, Moore, Richard A, Calarco, John A, Stein, Lincoln D, Bader, Gary D, Reimand, Jüri, Ragoussis, Jiannis, Weiss, William A, Marra, Marco A, Suzuki, Hiromichi, and Taylor, Michael D

Subjects
Humans, Medulloblastoma, Cerebellar Neoplasms, Signal Transduction, Gene Expression Regulation, Neoplastic, Adolescent, Adult, Middle Aged, Child, Child, Preschool, Infant, Female, Male, Hedgehog Proteins, Gene Regulatory Networks, Genetic Variation, Young Adult, Transcriptome, Pediatric Research Initiative, Brain Cancer, Pediatric, Rare Diseases, Genetics, Pediatric Cancer, Clinical Research, Brain Disorders, Neurosciences, Biotechnology, Human Genome, Cancer, 2.1 Biological and endogenous factors
Abstract

Sonic hedgehog medulloblastoma encompasses a clinically and molecularly diverse group of cancers of the developing central nervous system. Here, we use unbiased sequencing of the transcriptome across a large cohort of 250 tumors to reveal differences among molecular subtypes of the disease, and demonstrate the previously unappreciated importance of non-coding RNA transcripts. We identify alterations within the cAMP dependent pathway (GNAS, PRKAR1A) which converge on GLI2 activity and show that 18% of tumors have a genetic event that directly targets the abundance and/or stability of MYCN. Furthermore, we discover an extensive network of fusions in focally amplified regions encompassing GLI2, and several loss-of-function fusions in tumor suppressor genes PTCH1, SUFU and NCOR1. Molecular convergence on a subset of genes by nucleotide variants, copy number aberrations, and gene fusions highlight the key roles of specific pathways in the pathogenesis of Sonic hedgehog medulloblastoma and open up opportunities for therapeutic intervention.

Published
2021

6. Engineering Genetic Predisposition in Human Neuroepithelial Stem Cells Recapitulates Medulloblastoma Tumorigenesis

Author

Huang, Miller, Tailor, Jignesh, Zhen, Qiqi, Gillmor, Aaron H, Miller, Matthew L, Weishaupt, Holger, Chen, Justin, Zheng, Tina, Nash, Emily K, McHenry, Lauren K, An, Zhenyi, Ye, Fubaiyang, Takashima, Yasuhiro, Clarke, James, Ayetey, Harold, Cavalli, Florence MG, Luu, Betty, Moriarity, Branden S, Ilkhanizadeh, Shirin, Chavez, Lukas, Yu, Chunying, Kurian, Kathreena M, Magnaldo, Thierry, Sevenet, Nicolas, Koch, Philipp, Pollard, Steven M, Dirks, Peter, Snyder, Michael P, Largaespada, David A, Cho, Yoon Jae, Phillips, Joanna J, Swartling, Fredrik J, Morrissy, A Sorana, Kool, Marcel, Pfister, Stefan M, Taylor, Michael D, Smith, Austin, and Weiss, William A

Subjects
Medical Biotechnology, Biomedical and Clinical Sciences, Oncology and Carcinogenesis, Genetics, Human Genome, Brain Disorders, Regenerative Medicine, Pediatric, Pediatric Cancer, Stem Cell Research, Transplantation, Biotechnology, Rare Diseases, Stem Cell Research - Nonembryonic - Human, Cancer, Neurosciences, Stem Cell Research - Nonembryonic - Non-Human, Brain Cancer, Development of treatments and therapeutic interventions, 5.2 Cellular and gene therapies, Animals, Basal Cell Nevus Syndrome, Brain Neoplasms, Carcinogenesis, DEAD-box RNA Helicases, Disease Models, Animal, Genetic Engineering, Genetic Predisposition to Disease, Humans, Medulloblastoma, Mice, Mice, SCID, N-Myc Proto-Oncogene Protein, Neoplasm Proteins, Neural Stem Cells, Neuroepithelial Cells, Patched-1 Receptor, Pluripotent Stem Cells, Stem Cell Transplantation, Transplantation, Heterologous, SHH, human pluripotent stem cells, medulloblastoma, neuroepithelial stem cells, Biological Sciences, Medical and Health Sciences, Developmental Biology, Biological sciences, Biomedical and clinical sciences
Abstract

Human neural stem cell cultures provide progenitor cells that are potential cells of origin for brain cancers. However, the extent to which genetic predisposition to tumor formation can be faithfully captured in stem cell lines is uncertain. Here, we evaluated neuroepithelial stem (NES) cells, representative of cerebellar progenitors. We transduced NES cells with MYCN, observing medulloblastoma upon orthotopic implantation in mice. Significantly, transcriptomes and patterns of DNA methylation from xenograft tumors were globally more representative of human medulloblastoma compared to a MYCN-driven genetically engineered mouse model. Orthotopic transplantation of NES cells generated from Gorlin syndrome patients, who are predisposed to medulloblastoma due to germline-mutated PTCH1, also generated medulloblastoma. We engineered candidate cooperating mutations in Gorlin NES cells, with mutation of DDX3X or loss of GSE1 both accelerating tumorigenesis. These findings demonstrate that human NES cells provide a potent experimental resource for dissecting genetic causation in medulloblastoma.

Published
2019

8. Measuring Interactional Quality in Pre-School Settings: Introduction and Validation of the Sustained Shared Thinking and Emotional Wellbeing (SSTEW) Scale

Author

Howard, Steven J., Siraj, Iram, Melhuish, Edward C., Kingston, Denise, Neilsen-Hewett, Cathrine, de Rosnay, Marc, Duursma, Elisabeth, and Luu, Betty

Abstract

Research increasingly acknowledges the importance of high quality interactions that support and extend children's thinking. Few measurement tools currently exist, however, to capture this specific aspect of process quality. The Sustained Shared Thinking and Emotional Wellbeing (SSTEW) scale was developed to assess interactional quality in early childhood education and care, and it includes dimensions of process quality based on developmental theories and practice in effective settings. This study compared ratings on the SSTEW and Early Childhood Environment Rating Scale -- Extension (ECERS-E) to consider the impact of varying levels of curricular and interactional quality on child development in 45 Australian pre-school centres; namely the language, numeracy and socio-behavioural development of 669 children at the end of their pre-school year. Results indicated a level of predictive validity for interactional quality ratings as measured by SSTEW which, while related to curricular quality ratings on ECERS-E, differed in associations across domains of child development.

Published
2020
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9. Heterogeneity within the PF-EPN-B ependymoma subgroup

Author

Cavalli, Florence MG, Hübner, Jens-Martin, Sharma, Tanvi, Luu, Betty, Sill, Martin, Zapotocky, Michal, Mack, Stephen C, Witt, Hendrik, Lin, Tong, Shih, David JH, Ho, Ben, Santi, Mariarita, Emery, Lyndsey, Hukin, Juliette, Dunham, Christopher, McLendon, Roger E, Lipp, Eric S, Gururangan, Sridharan, Grossbach, Andrew, French, Pim, Kros, Johan M, van Veelen, Marie-Lise C, Rao, Amulya A Nageswara, Giannini, Caterina, Leary, Sarah, Jung, Shin, Faria, Claudia C, Mora, Jaume, Schüller, Ulrich, Alonso, Marta M, Chan, Jennifer A, Klekner, Almos, Chambless, Lola B, Hwang, Eugene I, Massimino, Maura, Eberhart, Charles G, Karajannis, Matthias A, Lu, Benjamin, Liau, Linda M, Zollo, Massimo, Ferrucci, Veronica, Carlotti, Carlos, Tirapelli, Daniela PC, Tabori, Uri, Bouffet, Eric, Ryzhova, Marina, Ellison, David W, Merchant, Thomas E, Gilbert, Mark R, Armstrong, Terri S, Korshunov, Andrey, Pfister, Stefan M, Taylor, Michael D, Aldape, Kenneth, Pajtler, Kristian W, Kool, Marcel, and Ramaswamy, Vijay

Subjects
Genetics, Cancer, Clinical Research, Rare Diseases, Human Genome, Brain Cancer, Brain Disorders, Adolescent, Adult, Age Factors, Child, Cohort Studies, DNA Copy Number Variations, DNA Methylation, Ependymoma, Female, Gene Expression Profiling, Humans, Infratentorial Neoplasms, Kaplan-Meier Estimate, Male, Microarray Analysis, Middle Aged, Young Adult, Posterior fossa, Subgrouping, PFB, PFA, Clustering, Clinical Sciences, Neurosciences, Neurology & Neurosurgery
Abstract

Posterior fossa ependymoma comprise three distinct molecular variants, termed PF-EPN-A (PFA), PF-EPN-B (PFB), and PF-EPN-SE (subependymoma). Clinically, they are very disparate and PFB tumors are currently being considered for a trial of radiation avoidance. However, to move forward, unraveling the heterogeneity within PFB would be highly desirable. To discern the molecular heterogeneity within PFB, we performed an integrated analysis consisting of DNA methylation profiling, copy-number profiling, gene expression profiling, and clinical correlation across a cohort of 212 primary posterior fossa PFB tumors. Unsupervised spectral clustering and t-SNE analysis of genome-wide methylation data revealed five distinct subtypes of PFB tumors, termed PFB1-5, with distinct demographics, copy-number alterations, and gene expression profiles. All PFB subtypes were distinct from PFA and posterior fossa subependymomas. Of the five subtypes, PFB4 and PFB5 are more discrete, consisting of younger and older patients, respectively, with a strong female-gender enrichment in PFB5 (age: p = 0.011, gender: p = 0.04). Broad copy-number aberrations were common; however, many events such as chromosome 2 loss, 5 gain, and 17 loss were enriched in specific subtypes and 1q gain was enriched in PFB1. Late relapses were common across all five subtypes, but deaths were uncommon and present in only two subtypes (PFB1 and PFB3). Unlike the case in PFA ependymoma, 1q gain was not a robust marker of poor progression-free survival; however, chromosome 13q loss may represent a novel marker for risk stratification across the spectrum of PFB subtypes. Similar to PFA ependymoma, there exists a significant intertumoral heterogeneity within PFB, with distinct molecular subtypes identified. Even when accounting for this heterogeneity, extent of resection remains the strongest predictor of poor outcome. However, this biological heterogeneity must be accounted for in future preclinical modeling and personalized therapies.

Published
2018

10. A Hematogenous Route for Medulloblastoma Leptomeningeal Metastases

Author

Garzia, Livia, Kijima, Noriyuki, Morrissy, A Sorana, De Antonellis, Pasqualino, Guerreiro-Stucklin, Ana, Holgado, Borja L, Wu, Xiaochong, Wang, Xin, Parsons, Michael, Zayne, Kory, Manno, Alex, Kuzan-Fischer, Claudia, Nor, Carolina, Donovan, Laura K, Liu, Jessica, Qin, Lei, Garancher, Alexandra, Liu, Kun-Wei, Mansouri, Sheila, Luu, Betty, Thompson, Yuan Yao, Ramaswamy, Vijay, Peacock, John, Farooq, Hamza, Skowron, Patryk, Shih, David JH, Li, Angela, Ensan, Sherine, Robbins, Clinton S, Cybulsky, Myron, Mitra, Siddhartha, Ma, Yussanne, Moore, Richard, Mungall, Andy, Cho, Yoon-Jae, Weiss, William A, Chan, Jennifer A, Hawkins, Cynthia E, Massimino, Maura, Jabado, Nada, Zapotocky, Michal, Sumerauer, David, Bouffet, Eric, Dirks, Peter, Tabori, Uri, Sorensen, Poul HB, Brastianos, Priscilla K, Aldape, Kenneth, Jones, Steven JM, Marra, Marco A, Woodgett, James R, Wechsler-Reya, Robert J, Fults, Daniel W, and Taylor, Michael D

Subjects
Brain Cancer, Cancer, Neurosciences, Pediatric Cancer, Pediatric, Rare Diseases, Brain Disorders, Allografts, Animals, Cell Line, Tumor, Chemokine CCL2, Chromosomes, Human, Pair 10, Female, Humans, Male, Medulloblastoma, Meningeal Neoplasms, Mice, SCID, Neoplastic Cells, Circulating, Parabiosis, brain tumors, circulating tumor cells, medulloblastoma, metastases, pediatric cancer, Biological Sciences, Medical and Health Sciences, Developmental Biology
Abstract

While the preponderance of morbidity and mortality in medulloblastoma patients are due to metastatic disease, most research focuses on the primary tumor due to a dearth of metastatic tissue samples and model systems. Medulloblastoma metastases are found almost exclusively on the leptomeningeal surface of the brain and spinal cord; dissemination is therefore thought to occur through shedding of primary tumor cells into the cerebrospinal fluid followed by distal re-implantation on the leptomeninges. We present evidence for medulloblastoma circulating tumor cells (CTCs) in therapy-naive patients and demonstrate in vivo, through flank xenografting and parabiosis, that medulloblastoma CTCs can spread through the blood to the leptomeningeal space to form leptomeningeal metastases. Medulloblastoma leptomeningeal metastases express high levels of the chemokine CCL2, and expression of CCL2 in medulloblastoma in vivo is sufficient to drive leptomeningeal dissemination. Hematogenous dissemination of medulloblastoma offers a new opportunity to diagnose and treat lethal disseminated medulloblastoma.

Published
2018

11. The whole-genome landscape of medulloblastoma subtypes

Author

Northcott, Paul A, Buchhalter, Ivo, Morrissy, A Sorana, Hovestadt, Volker, Weischenfeldt, Joachim, Ehrenberger, Tobias, Gröbner, Susanne, Segura-Wang, Maia, Zichner, Thomas, Rudneva, Vasilisa A, Warnatz, Hans-Jörg, Sidiropoulos, Nikos, Phillips, Aaron H, Schumacher, Steven, Kleinheinz, Kortine, Waszak, Sebastian M, Erkek, Serap, Jones, David TW, Worst, Barbara C, Kool, Marcel, Zapatka, Marc, Jäger, Natalie, Chavez, Lukas, Hutter, Barbara, Bieg, Matthias, Paramasivam, Nagarajan, Heinold, Michael, Gu, Zuguang, Ishaque, Naveed, Jäger-Schmidt, Christina, Imbusch, Charles D, Jugold, Alke, Hübschmann, Daniel, Risch, Thomas, Amstislavskiy, Vyacheslav, Gonzalez, Francisco German Rodriguez, Weber, Ursula D, Wolf, Stephan, Robinson, Giles W, Zhou, Xin, Wu, Gang, Finkelstein, David, Liu, Yanling, Cavalli, Florence MG, Luu, Betty, Ramaswamy, Vijay, Wu, Xiaochong, Koster, Jan, Ryzhova, Marina, Cho, Yoon-Jae, Pomeroy, Scott L, Herold-Mende, Christel, Schuhmann, Martin, Ebinger, Martin, Liau, Linda M, Mora, Jaume, McLendon, Roger E, Jabado, Nada, Kumabe, Toshihiro, Chuah, Eric, Ma, Yussanne, Moore, Richard A, Mungall, Andrew J, Mungall, Karen L, Thiessen, Nina, Tse, Kane, Wong, Tina, Jones, Steven JM, Witt, Olaf, Milde, Till, Von Deimling, Andreas, Capper, David, Korshunov, Andrey, Yaspo, Marie-Laure, Kriwacki, Richard, Gajjar, Amar, Zhang, Jinghui, Beroukhim, Rameen, Fraenkel, Ernest, Korbel, Jan O, Brors, Benedikt, Schlesner, Matthias, Eils, Roland, Marra, Marco A, Pfister, Stefan M, Taylor, Michael D, and Lichter, Peter

Subjects
Cancer, Human Genome, Brain Disorders, Pediatric Cancer, Brain Cancer, Genetics, Biotechnology, Rare Diseases, Neurosciences, Pediatric, Aetiology, 2.1 Biological and endogenous factors, Development of treatments and therapeutic interventions, 5.1 Pharmaceuticals, Good Health and Well Being, Carcinogenesis, Carrier Proteins, Cohort Studies, DNA Methylation, DNA Mutational Analysis, Datasets as Topic, Epistasis, Genetic, Genome, Human, Genomics, Humans, Medulloblastoma, Molecular Targeted Therapy, Muscle Proteins, Mutation, Oncogenes, Transcription Factors, Whole Genome Sequencing, Wnt Proteins, General Science & Technology
Abstract

Current therapies for medulloblastoma, a highly malignant childhood brain tumour, impose debilitating effects on the developing child, and highlight the need for molecularly targeted treatments with reduced toxicity. Previous studies have been unable to identify the full spectrum of driver genes and molecular processes that operate in medulloblastoma subgroups. Here we analyse the somatic landscape across 491 sequenced medulloblastoma samples and the molecular heterogeneity among 1,256 epigenetically analysed cases, and identify subgroup-specific driver alterations that include previously undiscovered actionable targets. Driver mutations were confidently assigned to most patients belonging to Group 3 and Group 4 medulloblastoma subgroups, greatly enhancing previous knowledge. New molecular subtypes were differentially enriched for specific driver events, including hotspot in-frame insertions that target KBTBD4 and 'enhancer hijacking' events that activate PRDM6. Thus, the application of integrative genomics to an extensive cohort of clinical samples derived from a single childhood cancer entity revealed a series of cancer genes and biologically relevant subtype diversity that represent attractive therapeutic targets for the treatment of patients with medulloblastoma.

Published
2017

12. Intertumoral Heterogeneity within Medulloblastoma Subgroups

Author

Cavalli, Florence MG, Remke, Marc, Rampasek, Ladislav, Peacock, John, Shih, David JH, Luu, Betty, Garzia, Livia, Torchia, Jonathon, Nor, Carolina, Morrissy, A Sorana, Agnihotri, Sameer, Thompson, Yuan Yao, Kuzan-Fischer, Claudia M, Farooq, Hamza, Isaev, Keren, Daniels, Craig, Cho, Byung-Kyu, Kim, Seung-Ki, Wang, Kyu-Chang, Lee, Ji Yeoun, Grajkowska, Wieslawa A, Perek-Polnik, Marta, Vasiljevic, Alexandre, Faure-Conter, Cecile, Jouvet, Anne, Giannini, Caterina, Rao, Amulya A Nageswara, Li, Kay Ka Wai, Ng, Ho-Keung, Eberhart, Charles G, Pollack, Ian F, Hamilton, Ronald L, Gillespie, G Yancey, Olson, James M, Leary, Sarah, Weiss, William A, Lach, Boleslaw, Chambless, Lola B, Thompson, Reid C, Cooper, Michael K, Vibhakar, Rajeev, Hauser, Peter, van Veelen, Marie-Lise C, Kros, Johan M, French, Pim J, Ra, Young Shin, Kumabe, Toshihiro, López-Aguilar, Enrique, Zitterbart, Karel, Sterba, Jaroslav, Finocchiaro, Gaetano, Massimino, Maura, Van Meir, Erwin G, Osuka, Satoru, Shofuda, Tomoko, Klekner, Almos, Zollo, Massimo, Leonard, Jeffrey R, Rubin, Joshua B, Jabado, Nada, Albrecht, Steffen, Mora, Jaume, Van Meter, Timothy E, Jung, Shin, Moore, Andrew S, Hallahan, Andrew R, Chan, Jennifer A, Tirapelli, Daniela PC, Carlotti, Carlos G, Fouladi, Maryam, Pimentel, José, Faria, Claudia C, Saad, Ali G, Massimi, Luca, Liau, Linda M, Wheeler, Helen, Nakamura, Hideo, Elbabaa, Samer K, Perezpeña-Diazconti, Mario, de León, Fernando Chico Ponce, Robinson, Shenandoah, Zapotocky, Michal, Lassaletta, Alvaro, Huang, Annie, Hawkins, Cynthia E, Tabori, Uri, Bouffet, Eric, Bartels, Ute, Dirks, Peter B, Rutka, James T, Bader, Gary D, Reimand, Jüri, Goldenberg, Anna, Ramaswamy, Vijay, and Taylor, Michael D

Subjects
Genetics, Rare Diseases, Pediatric Cancer, Cancer, Brain Cancer, Pediatric Research Initiative, Pediatric, Human Genome, Brain Disorders, Cluster Analysis, Cohort Studies, DNA Copy Number Variations, DNA Methylation, Gene Expression Profiling, Genomics, Humans, Medulloblastoma, Precision Medicine, copy number, gene expression, integrative clustering, medulloblastoma, methylation, subgroups, Neurosciences, Oncology and Carcinogenesis, Oncology & Carcinogenesis
Abstract

While molecular subgrouping has revolutionized medulloblastoma classification, the extent of heterogeneity within subgroups is unknown. Similarity network fusion (SNF) applied to genome-wide DNA methylation and gene expression data across 763 primary samples identifies very homogeneous clusters of patients, supporting the presence of medulloblastoma subtypes. After integration of somatic copy-number alterations, and clinical features specific to each cluster, we identify 12 different subtypes of medulloblastoma. Integrative analysis using SNF further delineates group 3 from group 4 medulloblastoma, which is not as readily apparent through analyses of individual data types. Two clear subtypes of infants with Sonic Hedgehog medulloblastoma with disparate outcomes and biology are identified. Medulloblastoma subtypes identified through integrative clustering have important implications for stratification of future clinical trials.

Published
2017

13. Author Correction: Locoregional delivery of CAR T cells to the cerebrospinal fluid for treatment of metastatic medulloblastoma and ependymoma

Author

Donovan, Laura K., Delaidelli, Alberto, Joseph, Sujith K., Bielamowicz, Kevin, Fousek, Kristen, Holgado, Borja L., Manno, Alex, Srikanthan, Dilakshan, Gad, Ahmed Z., Van Ommeren, Randy, Przelicki, David, Richman, Cory, Ramaswamy, Vijay, Daniels, Craig, Pallota, Jonelle G., Douglas, Tajana, Joynt, Alyssa C. M., Haapasalo, Joonas, Nor, Carolina, Vladoiu, Maria C., Kuzan-Fischer, Claudia M., Garzia, Livia, Mack, Stephen C., Varadharajan, Srinidhi, Baker, Matthew L., Hendrikse, Liam, Ly, Michelle, Kharas, Kaitlin, Balin, Polina, Wu, Xiaochong, Qin, Lei, Huang, Ning, Stucklin, Ana Guerreiro, Morrissy, A. Sorana, Cavalli, Florence M. G., Luu, Betty, Suarez, Raul, De Antonellis, Pasqualino, Michealraj, Antony, Rastan, Avesta, Hegde, Meenakshi, Komosa, Martin, Sirbu, Olga, Kumar, Sachin A., Abdullaev, Zied, Faria, Claudia C., Yip, Stephen, Hukin, Juliette, Tabori, Uri, Hawkins, Cynthia, Aldape, Ken, Daugaard, Mads, Maris, John M., Sorensen, Poul H., Ahmed, Nabil, and Taylor, Michael D.

Published
2021
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15. Author Correction: Failure of human rhombic lip differentiation underlies medulloblastoma formation

Author

Hendrikse, Liam D., Haldipur, Parthiv, Saulnier, Olivier, Millman, Jake, Sjoboen, Alexandria H., Erickson, Anders W., Ong, Winnie, Gordon, Victor, Coudière-Morrison, Ludivine, Mercier, Audrey L., Shokouhian, Mohammad, Suárez, Raúl A., Ly, Michelle, Borlase, Stephanie, Scott, David S., Vladoiu, Maria C., Farooq, Hamza, Sirbu, Olga, Nakashima, Takuma, Nambu, Shohei, Funakoshi, Yusuke, Bahcheli, Alec, Diaz-Mejia, J. Javier, Golser, Joseph, Bach, Kathleen, Phuong-Bao, Tram, Skowron, Patryk, Wang, Evan Y., Kumar, Sachin A., Balin, Polina, Visvanathan, Abhirami, Lee, John J. Y., Ayoub, Ramy, Chen, Xin, Chen, Xiaodi, Mungall, Karen L., Luu, Betty, Bérubé, Pierre, Wang, Yu C., Pfister, Stefan M., Kim, Seung-Ki, Delattre, Olivier, Bourdeaut, Franck, Doz, François, Masliah-Planchon, Julien, Grajkowska, Wieslawa A., Loukides, James, Dirks, Peter, Fèvre-Montange, Michelle, Jouvet, Anne, French, Pim J., Kros, Johan M., Zitterbart, Karel, Bailey, Swneke D., Eberhart, Charles G., Rao, Amulya A. N., Giannini, Caterina, Olson, James M., Garami, Miklós, Hauser, Peter, Phillips, Joanna J., Ra, Young S., de Torres, Carmen, Mora, Jaume, Li, Kay K. W., Ng, Ho-Keung, Poon, Wai S., Pollack, Ian F., López-Aguilar, Enrique, Gillespie, G. Yancey, Van Meter, Timothy E., Shofuda, Tomoko, Vibhakar, Rajeev, Thompson, Reid C., Cooper, Michael K., Rubin, Joshua B., Kumabe, Toshihiro, Jung, Shin, Lach, Boleslaw, Iolascon, Achille, Ferrucci, Veronica, de Antonellis, Pasqualino, Zollo, Massimo, Cinalli, Giuseppe, Robinson, Shenandoah, Stearns, Duncan S., Van Meir, Erwin G., Porrati, Paola, Finocchiaro, Gaetano, Massimino, Maura, Carlotti, Carlos G., Faria, Claudia C., Roussel, Martine F., Boop, Frederick, Chan, Jennifer A., Aldinger, Kimberly A., Razavi, Ferechte, Silvestri, Evelina, McLendon, Roger E., Thompson, Eric M., Ansari, Marc, Garre, Maria L., Chico, Fernando, Eguía, Pilar, Pérezpeña, Mario, Morrissy, A. Sorana, Cavalli, Florence M. G., Wu, Xiaochong, Daniels, Craig, Rich, Jeremy N., Jones, Steven J. M., Moore, Richard A., Marra, Marco A., Huang, Xi, Reimand, Jüri, Sorensen, Poul H., Wechsler-Reya, Robert J., Weiss, William A., Pugh, Trevor J., Garzia, Livia, Kleinman, Claudia L., Stein, Lincoln D., Jabado, Nada, Malkin, David, Ayrault, Olivier, Golden, Jeffrey A., Ellison, David W., Doble, Brad, Ramaswamy, Vijay, Werbowetski-Ogilvie, Tamra E., Suzuki, Hiromichi, Millen, Kathleen J., and Taylor, Michael D.

Published
2022
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16. Therapeutic Impact of Cytoreductive Surgery and Irradiation of Posterior Fossa Ependymoma in the Molecular Era: A Retrospective Multicohort Analysis.

Author

Ramaswamy, Vijay, Hielscher, Thomas, Mack, Stephen C, Lassaletta, Alvaro, Lin, Tong, Pajtler, Kristian W, Jones, David TW, Luu, Betty, Cavalli, Florence MG, Aldape, Kenneth, Remke, Marc, Mynarek, Martin, Rutkowski, Stefan, Gururangan, Sridharan, McLendon, Roger E, Lipp, Eric S, Dunham, Christopher, Hukin, Juliette, Eisenstat, David D, Fulton, Dorcas, van Landeghem, Frank KH, Santi, Mariarita, van Veelen, Marie-Lise C, Van Meir, Erwin G, Osuka, Satoru, Fan, Xing, Muraszko, Karin M, Tirapelli, Daniela PC, Oba-Shinjo, Sueli M, Marie, Suely KN, Carlotti, Carlos G, Lee, Ji Yeoun, Rao, Amulya A Nageswara, Giannini, Caterina, Faria, Claudia C, Nunes, Sofia, Mora, Jaume, Hamilton, Ronald L, Hauser, Peter, Jabado, Nada, Petrecca, Kevin, Jung, Shin, Massimi, Luca, Zollo, Massimo, Cinalli, Giuseppe, Bognár, László, Klekner, Almos, Hortobágyi, Tibor, Leary, Sarah, Ermoian, Ralph P, Olson, James M, Leonard, Jeffrey R, Gardner, Corrine, Grajkowska, Wieslawa A, Chambless, Lola B, Cain, Jason, Eberhart, Charles G, Ahsan, Sama, Massimino, Maura, Giangaspero, Felice, Buttarelli, Francesca R, Packer, Roger J, Emery, Lyndsey, Yong, William H, Soto, Horacio, Liau, Linda M, Everson, Richard, Grossbach, Andrew, Shalaby, Tarek, Grotzer, Michael, Karajannis, Matthias A, Zagzag, David, Wheeler, Helen, von Hoff, Katja, Alonso, Marta M, Tuñon, Teresa, Schüller, Ulrich, Zitterbart, Karel, Sterba, Jaroslav, Chan, Jennifer A, Guzman, Miguel, Elbabaa, Samer K, Colman, Howard, Dhall, Girish, Fisher, Paul G, Fouladi, Maryam, Gajjar, Amar, Goldman, Stewart, Hwang, Eugene, Kool, Marcel, Ladha, Harshad, Vera-Bolanos, Elizabeth, Wani, Khalida, Lieberman, Frank, Mikkelsen, Tom, Omuro, Antonio M, Pollack, Ian F, Prados, Michael, Robins, H Ian, and Soffietti, Riccardo

Subjects
Humans, Ependymoma, Infratentorial Neoplasms, Combined Modality Therapy, Retrospective Studies, Cohort Studies, Adolescent, Adult, Child, Child, Preschool, Infant, Female, Male, Cytoreduction Surgical Procedures, Rare Diseases, Pediatric Cancer, Cancer, Pediatric, Patient Safety, Clinical Sciences, Oncology and Carcinogenesis, Oncology & Carcinogenesis
Abstract

PurposePosterior fossa ependymoma comprises two distinct molecular variants termed EPN_PFA and EPN_PFB that have a distinct biology and natural history. The therapeutic value of cytoreductive surgery and radiation therapy for posterior fossa ependymoma after accounting for molecular subgroup is not known.MethodsFour independent nonoverlapping retrospective cohorts of posterior fossa ependymomas (n = 820) were profiled using genome-wide methylation arrays. Risk stratification models were designed based on known clinical and newly described molecular biomarkers identified by multivariable Cox proportional hazards analyses.ResultsMolecular subgroup is a powerful independent predictor of outcome even when accounting for age or treatment regimen. Incompletely resected EPN_PFA ependymomas have a dismal prognosis, with a 5-year progression-free survival ranging from 26.1% to 56.8% across all four cohorts. Although first-line (adjuvant) radiation is clearly beneficial for completely resected EPN_PFA, a substantial proportion of patients with EPN_PFB can be cured with surgery alone, and patients with relapsed EPN_PFB can often be treated successfully with delayed external-beam irradiation.ConclusionThe most impactful biomarker for posterior fossa ependymoma is molecular subgroup affiliation, independent of other demographic or treatment variables. However, both EPN_PFA and EPN_PFB still benefit from increased extent of resection, with the survival rates being particularly poor for subtotally resected EPN_PFA, even with adjuvant radiation therapy. Patients with EPN_PFB who undergo gross total resection are at lower risk for relapse and should be considered for inclusion in a randomized clinical trial of observation alone with radiation reserved for those who experience recurrence.

Published
2016

17. Prognostic value of medulloblastoma extent of resection after accounting for molecular subgroup: a retrospective integrated clinical and molecular analysis

Author

Thompson, Eric M, Hielscher, Thomas, Bouffet, Eric, Remke, Marc, Luu, Betty, Gururangan, Sridharan, McLendon, Roger E, Bigner, Darell D, Lipp, Eric S, Perreault, Sebastien, Cho, Yoon-Jae, Grant, Gerald, Kim, Seung-Ki, Lee, Ji Yeoun, Rao, Amulya A Nageswara, Giannini, Caterina, Li, Kay Ka Wai, Ng, Ho-Keung, Yao, Yu, Kumabe, Toshihiro, Tominaga, Teiji, Grajkowska, Wieslawa A, Perek-Polnik, Marta, Low, David CY, Seow, Wan Tew, Chang, Kenneth TE, Mora, Jaume, Pollack, Ian F, Hamilton, Ronald L, Leary, Sarah, Moore, Andrew S, Ingram, Wendy J, Hallahan, Andrew R, Jouvet, Anne, Fèvre-Montange, Michelle, Vasiljevic, Alexandre, Faure-Conter, Cecile, Shofuda, Tomoko, Kagawa, Naoki, Hashimoto, Naoya, Jabado, Nada, Weil, Alexander G, Gayden, Tenzin, Wataya, Takafumi, Shalaby, Tarek, Grotzer, Michael, Zitterbart, Karel, Sterba, Jaroslav, Kren, Leos, Hortobágyi, Tibor, Klekner, Almos, László, Bognár, Pócza, Tímea, Hauser, Peter, Schüller, Ulrich, Jung, Shin, Jang, Woo-Youl, French, Pim J, Kros, Johan M, van Veelen, Marie-Lise C, Massimi, Luca, Leonard, Jeffrey R, Rubin, Joshua B, Vibhakar, Rajeev, Chambless, Lola B, Cooper, Michael K, Thompson, Reid C, Faria, Claudia C, Carvalho, Alice, Nunes, Sofia, Pimentel, José, Fan, Xing, Muraszko, Karin M, López-Aguilar, Enrique, Lyden, David, Garzia, Livia, Shih, David JH, Kijima, Noriyuki, Schneider, Christian, Adamski, Jennifer, Northcott, Paul A, Kool, Marcel, Jones, David TW, Chan, Jennifer A, Nikolic, Ana, Garre, Maria Luisa, Van Meir, Erwin G, Osuka, Satoru, Olson, Jeffrey J, Jahangiri, Arman, Castro, Brandyn A, Gupta, Nalin, Weiss, William A, Moxon-Emre, Iska, Mabbott, Donald J, Lassaletta, Alvaro, Hawkins, Cynthia E, Tabori, Uri, Drake, James, and Kulkarni, Abhaya

Subjects
Biomedical and Clinical Sciences, Cardiovascular Medicine and Haematology, Clinical Sciences, Oncology and Carcinogenesis, Brain Disorders, Rare Diseases, Brain Cancer, Pediatric Research Initiative, Pediatric, Cancer, Adult, Brain Neoplasms, Canada, Child, Child, Preschool, Combined Modality Therapy, Disease Progression, Disease-Free Survival, Female, Humans, Infant, Magnetic Resonance Imaging, Male, Medulloblastoma, Prognosis, Retrospective Studies, Oncology & Carcinogenesis, Oncology and carcinogenesis
Abstract

BackgroundPatients with incomplete surgical resection of medulloblastoma are controversially regarded as having a marker of high-risk disease, which leads to patients undergoing aggressive surgical resections, so-called second-look surgeries, and intensified chemoradiotherapy. All previous studies assessing the clinical importance of extent of resection have not accounted for molecular subgroup. We analysed the prognostic value of extent of resection in a subgroup-specific manner.MethodsWe retrospectively identified patients who had a histological diagnosis of medulloblastoma and complete data about extent of resection and survival from centres participating in the Medulloblastoma Advanced Genomics International Consortium. We collected from resections done between April, 1997, and February, 2013, at 35 international institutions. We established medulloblastoma subgroup affiliation by gene expression profiling on frozen or formalin-fixed paraffin-embedded tissues. We classified extent of resection on the basis of postoperative imaging as gross total resection (no residual tumour), near-total resection (30 Gy vs no craniospinal irradiation). The primary analysis outcome was the effect of extent of resection by molecular subgroup and the effects of other clinical variables on overall and progression-free survival.FindingsWe included 787 patients with medulloblastoma (86 with WNT tumours, 242 with SHH tumours, 163 with group 3 tumours, and 296 with group 4 tumours) in our multivariable Cox models of progression-free and overall survival. We found that the prognostic benefit of increased extent of resection for patients with medulloblastoma is attenuated after molecular subgroup affiliation is taken into account. We identified a progression-free survival benefit for gross total resection over sub-total resection (hazard ratio [HR] 1·45, 95% CI 1·07-1·96, p=0·16) but no overall survival benefit (HR 1·23, 0·87-1·72, p=0·24). We saw no progression-free survival or overall survival benefit for gross total resection compared with near-total resection (HR 1·05, 0·71-1·53, p=0·8158 for progression-free survival and HR 1·14, 0·75-1·72, p=0·55 for overall survival). No significant survival benefit existed for greater extent of resection for patients with WNT, SHH, or group 3 tumours (HR 1·03, 0·67-1·58, p=0·89 for sub-total resection vs gross total resection). For patients with group 4 tumours, gross total resection conferred a benefit to progression-free survival compared with sub-total resection (HR 1·97, 1·22-3·17, p=0·0056), especially for those with metastatic disease (HR 2·22, 1·00-4·93, p=0·050). However, gross total resection had no effect on overall survival compared with sub-total resection in patients with group 4 tumours (HR 1·67, 0·93-2·99, p=0·084).InterpretationThe prognostic benefit of increased extent of resection for patients with medulloblastoma is attenuated after molecular subgroup affiliation is taken into account. Although maximum safe surgical resection should remain the standard of care, surgical removal of small residual portions of medulloblastoma is not recommended when the likelihood of neurological morbidity is high because there is no definitive benefit to gross total resection compared with near-total resection.FundingCanadian Cancer Society Research Institute, Terry Fox Research Institute, Canadian Institutes of Health Research, National Institutes of Health, Pediatric Brain Tumor Foundation, and the Garron Family Chair in Childhood Cancer Research.

Published
2016

18. 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

19. Locoregional delivery of CAR T cells to the cerebrospinal fluid for treatment of metastatic medulloblastoma and ependymoma

Author

Donovan, Laura K., Delaidelli, Alberto, Joseph, Sujith K., Bielamowicz, Kevin, Fousek, Kristen, Holgado, Borja L., Manno, Alex, Srikanthan, Dilakshan, Gad, Ahmed Z., Van Ommeren, Randy, Przelicki, David, Richman, Cory, Ramaswamy, Vijay, Daniels, Craig, Pallota, Jonelle G., Douglas, Tajana, Joynt, Alyssa C.M., Haapasalo, Joonas, Nor, Carolina, Vladoiu, Maria C., Kuzan-Fischer, Claudia M., Garzia, Livia, Mack, Stephen C., Varadharajan, Srinidhi, Baker, Matthew L., Hendrikse, Liam, Ly, Michelle, Kharas, Kaitlin, Balin, Polina, Wu, Xiaochong, Qin, Lei, Huang, Ning, Stucklin, Ana Guerreiro, Morrissy, A. Sorana, Cavalli, Florence M.G., Luu, Betty, Suarez, Raul, De Antonellis, Pasqualino, Michealraj, Antony, Rastan, Avesta, Hegde, Meenakshi, Komosa, Martin, Sirbu, Olga, Kumar, Sachin A., Abdullaev, Zied, Faria, Claudia C., Yip, Stephen, Hukin, Juliette, Tabori, Uri, Hawkins, Cynthia, Aldape, Ken, Daugaard, Mads, Maris, John M., Sorenson, Poul H., Ahmed, Nabil, and Taylor, Michael D.

Subjects
T cells -- Health aspects -- Methods, Medulloblastoma -- Care and treatment, Metastasis -- Care and treatment, Cellular therapy -- Methods -- Health aspects, Immunotherapy -- Methods -- Health aspects, Antigens -- Health aspects, Cerebrospinal fluid -- Health aspects -- Methods, Biological sciences, Health
Abstract

Recurrent medulloblastoma and ependymoma are universally lethal, with no approved targeted therapies and few candidates presently under clinical evaluation. Nearly all recurrent medulloblastomas and posterior fossa group A (PFA) ependymomas are located adjacent to and bathed by the cerebrospinal fluid, presenting an opportunity for locoregional therapy, bypassing the blood-brain barrier. We identify three cell-surface targets, EPHA2, HER2 and interleukin 13 receptor [alpha]2, expressed on medulloblastomas and ependymomas, but not expressed in the normal developing brain. We validate intrathecal delivery of EPHA2, HER2 and interleukin 13 receptor [alpha]2 chimeric antigen receptor T cells as an effective treatment for primary, metastatic and recurrent group 3 medulloblastoma and PFA ependymoma xenografts in mouse models. Finally, we demonstrate that administration of these chimeric antigen receptor T cells into the cerebrospinal fluid, alone or in combination with azacytidine, is a highly effective therapy for multiple metastatic mouse models of group 3 medulloblastoma and PFA ependymoma, thereby providing a rationale for clinical trials of these approaches in humans. Intraventricularly delivered monovalent and trivalent CAR T cells exhibit greater therapeutic efficacy as compared with intravenously delivered CAR T cells in medulloblastoma xenograft mouse models and show potency in ependymoma xenograft mouse models., Author(s): Laura K. Donovan [sup.1] [sup.2] , Alberto Delaidelli [sup.3] , Sujith K. Joseph [sup.4] [sup.5] , Kevin Bielamowicz [sup.4] [sup.5] , Kristen Fousek [sup.4] [sup.5] , Borja L. Holgado [...]

Published
2020
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20. Recurrent noncoding U1 snRNA mutations drive cryptic splicing in SHH medulloblastoma

Author

Suzuki, Hiromichi, Kumar, Sachin A., Shuai, Shimin, Diaz-Navarro, Ander, Gutierrez-Fernandez, Ana, De Antonellis, Pasqualino, Cavalli, Florence M. G., Juraschka, Kyle, Farooq, Hamza, Shibahara, Ichiyo, Vladoiu, Maria C., Zhang, Jiao, Abeysundara, Namal, Przelicki, David, Skowron, Patryk, Gauer, Nicole, Luu, Betty, Daniels, Craig, Wu, Xiaochong, Forget, Antoine, Momin, Ali, Wang, Jun, Dong, Weifan, Kim, Seung-Ki, Grajkowska, Wieslawa A., Jouvet, Anne, Fèvre-Montange, Michelle, Garrè, Maria Luisa, Nageswara Rao, Amulya A., Giannini, Caterina, Kros, Johan M., French, Pim J., Jabado, Nada, Ng, Ho-Keung, Poon, Wai Sang, Eberhart, Charles G., Pollack, Ian F., Olson, James M., Weiss, William A., Kumabe, Toshihiro, López-Aguilar, Enrique, Lach, Boleslaw, Massimino, Maura, Van Meir, Erwin G., Rubin, Joshua B., Vibhakar, Rajeev, Chambless, Lola B., Kijima, Noriyuki, Klekner, Almos, Bognár, László, Chan, Jennifer A., Faria, Claudia C., Ragoussis, Jiannis, Pfister, Stefan M., Goldenberg, Anna, Wechsler-Reya, Robert J., Bailey, Swneke D., Garzia, Livia, Morrissy, A. Sorana, Marra, Marco A., Huang, Xi, Malkin, David, Ayrault, Olivier, Ramaswamy, Vijay, Puente, Xose S., Calarco, John A., Stein, Lincoln, and Taylor, Michael D.

Published
2019
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21. Cytogenetic prognostication within medulloblastoma subgroups.

Author

Shih, David, Northcott, Paul, Remke, Marc, Korshunov, Andrey, Ramaswamy, Vijay, Kool, Marcel, Luu, Betty, Yao, Yuan, Wang, Xin, Dubuc, Adrian, Garzia, Livia, Peacock, John, Mack, Stephen, Wu, Xiaochong, Rolider, Adi, Morrissy, A, Cavalli, Florence, Jones, David, Zitterbart, Karel, Faria, Claudia, Schüller, Ulrich, Kren, Leos, Kumabe, Toshihiro, Tominaga, Teiji, Shin Ra, Young, Garami, Miklós, Hauser, Peter, Chan, Jennifer, Robinson, Shenandoah, Bognár, László, Klekner, Almos, Saad, Ali, Albrecht, Steffen, Fontebasso, Adam, Cinalli, Giuseppe, De Antonellis, Pasqualino, Zollo, Massimo, Cooper, Michael, Thompson, Reid, Bailey, Simon, Lindsey, Janet, Di Rocco, Concezio, Massimi, Luca, Michiels, Erna, Scherer, Stephen, Lee, Ji-Yeoun, Cho, Byung-Kyu, Kim, Seung-Ki, Wang, Kyu-Chang, Leonard, Jeffrey, Rubin, Joshua, de Torres, Carmen, Lavarino, Cinzia, Mora, Jaume, Cho, Yoon-Jae, Tabori, Uri, Olson, James, Gajjar, Amar, Packer, Roger, Fan, Xing, Muraszko, Karin, Vibhakar, Rajeev, Eberhart, Charles, Fouladi, Maryam, Lach, Boleslaw, Jung, Shin, Wechsler-Reya, Robert, Fèvre-Montange, Michelle, Jouvet, Anne, Jabado, Nada, Pollack, Ian, Rutkowski, Stefan, Pomeroy, Scott, French, Pim, Kloosterhof, Nanne, Kros, Johan, Van Meir, Erwin, Clifford, Steven, Bourdeaut, Franck, Delattre, Olivier, Doz, François, Hawkins, Cynthia, Malkin, David, Grajkowska, Wieslawa, Perek-Polnik, Marta, Bouffet, Eric, Rutka, James, Pfister, Stefan, Taylor, Michael, Gupta, Nalin, Phillips, Joanna, Weiss, William, and Liau, Linda

Subjects
Adolescent, Biomarkers, Tumor, Child, Child, Preschool, Chromosomes, Human, Pair 11, Chromosomes, Human, Pair 14, Cytogenetics, Female, Gene Expression Profiling, Gene Expression Regulation, Neoplastic, Hedgehog Proteins, Humans, In Situ Hybridization, Fluorescence, Infant, Kruppel-Like Transcription Factors, Male, Medulloblastoma, Nuclear Proteins, Predictive Value of Tests, Prognosis, Proportional Hazards Models, Proto-Oncogene Proteins c-myc, Reproducibility of Results, Risk Assessment, Risk Factors, Tissue Array Analysis, Wnt Proteins, Young Adult, Zinc Finger Protein Gli2
Abstract

PURPOSE: Medulloblastoma comprises four distinct molecular subgroups: WNT, SHH, Group 3, and Group 4. Current medulloblastoma protocols stratify patients based on clinical features: patient age, metastatic stage, extent of resection, and histologic variant. Stark prognostic and genetic differences among the four subgroups suggest that subgroup-specific molecular biomarkers could improve patient prognostication. PATIENTS AND METHODS: Molecular biomarkers were identified from a discovery set of 673 medulloblastomas from 43 cities around the world. Combined risk stratification models were designed based on clinical and cytogenetic biomarkers identified by multivariable Cox proportional hazards analyses. Identified biomarkers were tested using fluorescent in situ hybridization (FISH) on a nonoverlapping medulloblastoma tissue microarray (n = 453), with subsequent validation of the risk stratification models. RESULTS: Subgroup information improves the predictive accuracy of a multivariable survival model compared with clinical biomarkers alone. Most previously published cytogenetic biomarkers are only prognostic within a single medulloblastoma subgroup. Profiling six FISH biomarkers (GLI2, MYC, chromosome 11 [chr11], chr14, 17p, and 17q) on formalin-fixed paraffin-embedded tissues, we can reliably and reproducibly identify very low-risk and very high-risk patients within SHH, Group 3, and Group 4 medulloblastomas. CONCLUSION: Combining subgroup and cytogenetic biomarkers with established clinical biomarkers substantially improves patient prognostication, even in the context of heterogeneous clinical therapies. The prognostic significance of most molecular biomarkers is restricted to a specific subgroup. We have identified a small panel of cytogenetic biomarkers that reliably identifies very high-risk and very low-risk groups of patients, making it an excellent tool for selecting patients for therapy intensification and therapy de-escalation in future clinical trials.

Published
2014

22. Effectively supporting Culturally and Linguistically Diverse (CALD) young people with their mental health and wellbeing – does this matter or exist in Australia?

Author

Luu, Betty, Fox, Levi, McVeigh, Mary Jo, and Ravulo, Jioji

Subjects
*PSYCHIATRIC diagnosis, *WELL-being, *CINAHL database, *PSYCHOLOGY information storage & retrieval systems, *MEDICAL databases, *HEALTH education, *PRIVACY, *MINORITIES, *HEALTH services accessibility, *SYSTEMATIC reviews, *COMMUNICATION barriers, *MENTAL health, *INDIVIDUALIZED medicine, *EMOTIONAL trauma, *CREATIVE ability, *SOCIAL stigma, *SELF-efficacy, *HEALTH literacy, *MEDICAL care use, *CULTURAL competence, *INTERPERSONAL relations, *HEALTH, *INFORMATION resources, *MEDICAL ethics, *PHYSICIAN practice patterns, *MEDLINE, *MENTAL health services, *ERIC (Information retrieval system), *SOCIAL integration
Abstract

This paper presents a systematic review that assessed the different types of mental health programs and interventions available for young people from Culturally and Linguistically Diverse (CALD) backgrounds in Australia, and identified core elements of practice for supporting the mental health of CALD youth, and key barriers that preclude CALD youth from engaging with mental health services. A total of 19 articles met inclusion criteria and a total of six distinct practices were identified: (1) personalization, identity and recognition of trauma; (2) creative expression; (3) cultural competence; (4) self-efficacy and empowerment; (5) social connections and relationships; and (6) information and content delivery. Key barriers related to engagement with CALD youth mental health programs included language and literacy barriers, stigma and shame, and service providers' limited cultural competency, and lack of diverse understandings of wellbeing. The findings from this review suggest several avenues for ensuring practice that effectively meets the unique mental health needs of CALD young people and reduces barriers to their access and engagement. [ABSTRACT FROM AUTHOR]

Published
2024
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23. TERT promoter mutations are highly recurrent in SHH subgroup medulloblastoma.

Author

Remke, Marc, Ramaswamy, Vijay, Peacock, John, Shih, David, Koelsche, Christian, Northcott, Paul, Hill, Nadia, Cavalli, Florence, Kool, Marcel, Wang, Xin, Mack, Stephen, Barszczyk, Mark, Morrissy, A, Wu, Xiaochong, Agnihotri, Sameer, Luu, Betty, Jones, David, Garzia, Livia, Dubuc, Adrian, Zhukova, Nataliya, Vanner, Robert, Kros, Johan, French, Pim, Van Meir, Erwin, Vibhakar, Rajeev, Zitterbart, Karel, Chan, Jennifer, Bognár, László, Klekner, Almos, Lach, Boleslaw, Jung, Shin, Saad, Ali, Albrecht, Steffen, Zollo, Massimo, Cooper, Michael, Thompson, Reid, Delattre, Oliver, Bourdeaut, Franck, Doz, François, Garami, Miklós, Hauser, Peter, Carlotti, Carlos, Van Meter, Timothy, Massimi, Luca, Fults, Daniel, Pomeroy, Scott, Kumabe, Toshiro, Ra, Young, Leonard, Jeffrey, Elbabaa, Samer, Mora, Jaume, Rubin, Joshua, Cho, Yoon-Jae, McLendon, Roger, Bigner, Darell, Eberhart, Charles, Fouladi, Maryam, Wechsler-Reya, Robert, Faria, Claudia, Croul, Sidney, Huang, Annie, Bouffet, Eric, Hawkins, Cynthia, Dirks, Peter, Schüller, Ulrich, Pollack, Ian, Rutkowski, Stefan, Meyronet, David, Jouvet, Anne, Fèvre-Montange, Michelle, Jabado, Nada, Perek-Polnik, Marta, Grajkowska, Wieslawa, Kim, Seung-Ki, Rutka, James, Malkin, David, Tabori, Uri, Pfister, Stefan, Korshunov, Andrey, von Deimling, Andreas, Taylor, Michael, Weiss, William, and Liau, Linda

Subjects
Adolescent, Adult, Brain Neoplasms, Child, Child, Preschool, DNA Mutational Analysis, Female, Gene Expression Profiling, Genotype, Humans, Infant, Male, Medulloblastoma, Middle Aged, Mutation, Prognosis, Promoter Regions, Genetic, Telomerase
Abstract

Telomerase reverse transcriptase (TERT) promoter mutations were recently shown to drive telomerase activity in various cancer types, including medulloblastoma. However, the clinical and biological implications of TERT mutations in medulloblastoma have not been described. Hence, we sought to describe these mutations and their impact in a subgroup-specific manner. We analyzed the TERT promoter by direct sequencing and genotyping in 466 medulloblastomas. The mutational distributions were determined according to subgroup affiliation, demographics, and clinical, prognostic, and molecular features. Integrated genomics approaches were used to identify specific somatic copy number alterations in TERT promoter-mutated and wild-type tumors. Overall, TERT promoter mutations were identified in 21 % of medulloblastomas. Strikingly, the highest frequencies of TERT mutations were observed in SHH (83 %; 55/66) and WNT (31 %; 4/13) medulloblastomas derived from adult patients. Group 3 and Group 4 harbored this alteration in

Published
2013

24. Subgroup-specific structural variation across 1,000 medulloblastoma genomes.

Author

Northcott, Paul, Shih, David, Peacock, John, Garzia, Livia, Morrissy, A, Zichner, Thomas, Stütz, Adrian, Korshunov, Andrey, Reimand, Jüri, Schumacher, Steven, Beroukhim, Rameen, Ellison, David, Marshall, Christian, Lionel, Anath, Mack, Stephen, Dubuc, Adrian, Yao, Yuan, Ramaswamy, Vijay, Luu, Betty, Rolider, Adi, Cavalli, Florence, Wang, Xin, Remke, Marc, Wu, Xiaochong, Chiu, Readman, Chu, Andy, Chuah, Eric, Corbett, Richard, Hoad, Gemma, Jackman, Shaun, Li, Yisu, Lo, Allan, Mungall, Karen, Nip, Ka, Qian, Jenny, Raymond, Anthony, Thiessen, Nina, Varhol, Richard, Birol, Inanc, Moore, Richard, Mungall, Andrew, Holt, Robert, Kawauchi, Daisuke, Roussel, Martine, Kool, Marcel, Jones, David, Witt, Hendrick, Fernandez-L, Africa, Kenney, Anna, Wechsler-Reya, Robert, Dirks, Peter, Aviv, Tzvi, Grajkowska, Wieslawa, Perek-Polnik, Marta, Haberler, Christine, Delattre, Olivier, Reynaud, Stéphanie, Doz, François, Pernet-Fattet, Sarah, Cho, Byung-Kyu, Kim, Seung-Ki, Wang, Kyu-Chang, Scheurlen, Wolfram, Eberhart, Charles, Fèvre-Montange, Michelle, Jouvet, Anne, Pollack, Ian, Fan, Xing, Muraszko, Karin, Gillespie, G, Di Rocco, Concezio, Massimi, Luca, Michiels, Erna, Kloosterhof, Nanne, French, Pim, Kros, Johan, Olson, James, Ellenbogen, Richard, Zitterbart, Karel, Kren, Leos, Thompson, Reid, Cooper, Michael, Lach, Boleslaw, McLendon, Roger, Bigner, Darell, Fontebasso, Adam, Albrecht, Steffen, Jabado, Nada, Lindsey, Janet, Bailey, Simon, Van Meir, Erwin, Fouladi, Maryam, Nakamura, Hideo, Cinalli, Giuseppe, Garami, Miklós, Hauser, Peter, Saad, Ali, Iolascon, Achille, Jung, Shin, and Carlotti, Carlos

Subjects
Carrier Proteins, Cerebellar Neoplasms, Child, DNA Copy Number Variations, Gene Duplication, Genes, myc, Genome, Human, Genomic Structural Variation, Genomics, Hedgehog Proteins, Humans, Medulloblastoma, NF-kappa B, Nerve Tissue Proteins, Oncogene Proteins, Fusion, Proteins, RNA, Long Noncoding, Signal Transduction, Transforming Growth Factor beta, Translocation, Genetic
Abstract

Medulloblastoma, the most common malignant paediatric brain tumour, is currently treated with nonspecific cytotoxic therapies including surgery, whole-brain radiation, and aggressive chemotherapy. As medulloblastoma exhibits marked intertumoural heterogeneity, with at least four distinct molecular variants, previous attempts to identify targets for therapy have been underpowered because of small samples sizes. Here we report somatic copy number aberrations (SCNAs) in 1,087 unique medulloblastomas. SCNAs are common in medulloblastoma, and are predominantly subgroup-enriched. The most common region of focal copy number gain is a tandem duplication of SNCAIP, a gene associated with Parkinsons disease, which is exquisitely restricted to Group 4α. Recurrent translocations of PVT1, including PVT1-MYC and PVT1-NDRG1, that arise through chromothripsis are restricted to Group 3. Numerous targetable SCNAs, including recurrent events targeting TGF-β signalling in Group 3, and NF-κB signalling in Group 4, suggest future avenues for rational, targeted therapy.

Published
2012

25. Therapeutic targeting of ependymoma as informed by oncogenic enhancer profiling

Author

Mack, Stephen C., Pajtler, Kristian W., Chavez, Lukas, Okonechnikov, Konstantin, Bertrand, Kelsey C., Wang, Xiuxing, Erkek, Serap, Federation, Alexander, Song, Anne, Lee, Christine, Wang, Xin, McDonald, Laura, Morrow, James J., Saiakhova, Alina, Sin-Chan, Patrick, Wu, Qiulian, Michaelraj, Kulandaimanuvel Antony, Miller, Tyler E., Hubert, Christopher G., Ryzhova, Marina, Garzia, Livia, Donovan, Laura, Dombrowski, Stephen, Factor, Daniel C., Luu, Betty, Valentim, Claudia L. L., Gimple, Ryan C., Morton, Andrew, Kim, Leo, Prager, Briana C., Lee, John J. Y., Wu, Xiaochong, Zuccaro, Jennifer, Thompson, Yuan, Holgado, Borja L., Reimand, Jri, Ke, Susan Q., Tropper, Adam, Lai, Sisi, Vijayarajah, Senthuran, Doan, Sylvia, Mahadev, Vaidehi, Mian, Ana Fernandez, Grbner, Susanne N., Lienhard, Matthias, Zapatka, Marc, Huang, Zhiqin, Aldape, Kenneth D., Carcaboso, Angel M., Houghton, Peter J., Keir, Stephen T., Milde, Till, Witt, Hendrik, Li, Yan, Li, Chao-Jun, Bian, Xiu-Wu, Jones, David T. W., Scott, Ian, Singh, Sheila K., Huang, Annie, Dirks, Peter B., Bouffet, Eric, Bradner, James E., Ramaswamy, Vijay, Jabado, Nada, Rutka, James T., Northcott, Paul A., Lupien, Mathieu, Lichter, Peter, Korshunov, Andrey, Scacheri, Peter C., Pfister, Stefan M., Kool, Marcel, Taylor, Michael D., and Rich, Jeremy N.

Subjects
Gliomas -- Physiological aspects -- Genetic aspects -- Care and treatment, Cancer genetics -- Research, Cancer research, Environmental issues, Science and technology, Zoology and wildlife conservation
Abstract

Author(s): Stephen C. Mack [1, 2, 3, 4]; Kristian W. Pajtler [5, 6, 7]; Lukas Chavez [5, 6, 8]; Konstantin Okonechnikov [5, 6]; Kelsey C. Bertrand [1, 2, 9]; Xiuxing [...]

Published
2018
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26. Supplementary File 1 from Intratumoral Genetic and Functional Heterogeneity in Pediatric Glioblastoma

Author

Hoffman, Mary, primary, Gillmor, Aaron H., primary, Kunz, Daniel J., primary, Johnston, Michael J., primary, Nikolic, Ana, primary, Narta, Kiran, primary, Zarrei, Mehdi, primary, King, Jennifer, primary, Ellestad, Katrina, primary, Dang, Ngoc Ha, primary, Cavalli, Florence M.G., primary, Kushida, Michelle M., primary, Coutinho, Fiona J., primary, Zhu, Yuankun, primary, Luu, Betty, primary, Ma, Yussanne, primary, Mungall, Andrew J., primary, Moore, Richard, primary, Marra, Marco A., primary, Taylor, Michael D., primary, Pugh, Trevor J., primary, Dirks, Peter B., primary, Strother, Douglas, primary, Lafay-Cousin, Lucie, primary, Resnick, Adam C., primary, Scherer, Stephen, primary, Senger, Donna L., primary, Simons, Benjamin D., primary, Chan, Jennifer A., primary, Morrissy, A. Sorana, primary, and Gallo, Marco, primary

Published
2023
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27. Data from A Novel Method for Rapid Molecular Subgrouping of Medulloblastoma

Author

Gómez, Soledad, primary, Garrido-Garcia, Alícia, primary, Garcia-Gerique, Laura, primary, Lemos, Isadora, primary, Suñol, Mariona, primary, de Torres, Carmen, primary, Kulis, Marta, primary, Pérez-Jaume, Sara, primary, Carcaboso, Ángel M., primary, Luu, Betty, primary, Kieran, Mark W., primary, Jabado, Nada, primary, Kozlenkov, Alexey, primary, Dracheva, Stella, primary, Ramaswamy, Vijay, primary, Hovestadt, Volker, primary, Johann, Pascal, primary, Jones, David T.W., primary, Pfister, Stefan M., primary, Morales La Madrid, Andrés, primary, Cruz, Ofelia, primary, Taylor, Michael D., primary, Martin-Subero, Jose-Ignacio, primary, Mora, Jaume, primary, and Lavarino, Cinzia, primary

Published
2023
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28. Supplementary Appendix from A Novel Method for Rapid Molecular Subgrouping of Medulloblastoma

Author

Gómez, Soledad, primary, Garrido-Garcia, Alícia, primary, Garcia-Gerique, Laura, primary, Lemos, Isadora, primary, Suñol, Mariona, primary, de Torres, Carmen, primary, Kulis, Marta, primary, Pérez-Jaume, Sara, primary, Carcaboso, Ángel M., primary, Luu, Betty, primary, Kieran, Mark W., primary, Jabado, Nada, primary, Kozlenkov, Alexey, primary, Dracheva, Stella, primary, Ramaswamy, Vijay, primary, Hovestadt, Volker, primary, Johann, Pascal, primary, Jones, David T.W., primary, Pfister, Stefan M., primary, Morales La Madrid, Andrés, primary, Cruz, Ofelia, primary, Taylor, Michael D., primary, Martin-Subero, Jose-Ignacio, primary, Mora, Jaume, primary, and Lavarino, Cinzia, primary

Published
2023
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29. Supplementary Data from Picosecond Infrared Laser Desorption Mass Spectrometry Identifies Medulloblastoma Subgroups on Intrasurgical Timescales

Author

Woolman, Michael, primary, Kuzan-Fischer, Claudia M., primary, Ferry, Isabelle, primary, Kiyota, Taira, primary, Luu, Betty, primary, Wu, Megan, primary, Munoz, David G., primary, Das, Sunit, primary, Aman, Ahmed, primary, Taylor, Michael D., primary, Rutka, James T., primary, Ginsberg, Howard J., primary, and Zarrine-Afsar, Arash, primary

Published
2023
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30. Data from Picosecond Infrared Laser Desorption Mass Spectrometry Identifies Medulloblastoma Subgroups on Intrasurgical Timescales

Author

Woolman, Michael, primary, Kuzan-Fischer, Claudia M., primary, Ferry, Isabelle, primary, Kiyota, Taira, primary, Luu, Betty, primary, Wu, Megan, primary, Munoz, David G., primary, Das, Sunit, primary, Aman, Ahmed, primary, Taylor, Michael D., primary, Rutka, James T., primary, Ginsberg, Howard J., primary, and Zarrine-Afsar, Arash, primary

Published
2023
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31. Supplementary File 2 from Intratumoral Genetic and Functional Heterogeneity in Pediatric Glioblastoma

Author

Hoffman, Mary, primary, Gillmor, Aaron H., primary, Kunz, Daniel J., primary, Johnston, Michael J., primary, Nikolic, Ana, primary, Narta, Kiran, primary, Zarrei, Mehdi, primary, King, Jennifer, primary, Ellestad, Katrina, primary, Dang, Ngoc Ha, primary, Cavalli, Florence M.G., primary, Kushida, Michelle M., primary, Coutinho, Fiona J., primary, Zhu, Yuankun, primary, Luu, Betty, primary, Ma, Yussanne, primary, Mungall, Andrew J., primary, Moore, Richard, primary, Marra, Marco A., primary, Taylor, Michael D., primary, Pugh, Trevor J., primary, Dirks, Peter B., primary, Strother, Douglas, primary, Lafay-Cousin, Lucie, primary, Resnick, Adam C., primary, Scherer, Stephen, primary, Senger, Donna L., primary, Simons, Benjamin D., primary, Chan, Jennifer A., primary, Morrissy, A. Sorana, primary, and Gallo, Marco, primary

Published
2023
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32. Supplementary Methods and Data from Intratumoral Genetic and Functional Heterogeneity in Pediatric Glioblastoma

Author

Hoffman, Mary, primary, Gillmor, Aaron H., primary, Kunz, Daniel J., primary, Johnston, Michael J., primary, Nikolic, Ana, primary, Narta, Kiran, primary, Zarrei, Mehdi, primary, King, Jennifer, primary, Ellestad, Katrina, primary, Dang, Ngoc Ha, primary, Cavalli, Florence M.G., primary, Kushida, Michelle M., primary, Coutinho, Fiona J., primary, Zhu, Yuankun, primary, Luu, Betty, primary, Ma, Yussanne, primary, Mungall, Andrew J., primary, Moore, Richard, primary, Marra, Marco A., primary, Taylor, Michael D., primary, Pugh, Trevor J., primary, Dirks, Peter B., primary, Strother, Douglas, primary, Lafay-Cousin, Lucie, primary, Resnick, Adam C., primary, Scherer, Stephen, primary, Senger, Donna L., primary, Simons, Benjamin D., primary, Chan, Jennifer A., primary, Morrissy, A. Sorana, primary, and Gallo, Marco, primary

Published
2023
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33. Data from Intratumoral Genetic and Functional Heterogeneity in Pediatric Glioblastoma

Author

Hoffman, Mary, primary, Gillmor, Aaron H., primary, Kunz, Daniel J., primary, Johnston, Michael J., primary, Nikolic, Ana, primary, Narta, Kiran, primary, Zarrei, Mehdi, primary, King, Jennifer, primary, Ellestad, Katrina, primary, Dang, Ngoc Ha, primary, Cavalli, Florence M.G., primary, Kushida, Michelle M., primary, Coutinho, Fiona J., primary, Zhu, Yuankun, primary, Luu, Betty, primary, Ma, Yussanne, primary, Mungall, Andrew J., primary, Moore, Richard, primary, Marra, Marco A., primary, Taylor, Michael D., primary, Pugh, Trevor J., primary, Dirks, Peter B., primary, Strother, Douglas, primary, Lafay-Cousin, Lucie, primary, Resnick, Adam C., primary, Scherer, Stephen, primary, Senger, Donna L., primary, Simons, Benjamin D., primary, Chan, Jennifer A., primary, Morrissy, A. Sorana, primary, and Gallo, Marco, primary

Published
2023
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34. Supplementary Tables from A Novel Method for Rapid Molecular Subgrouping of Medulloblastoma

Author

Gómez, Soledad, primary, Garrido-Garcia, Alícia, primary, Garcia-Gerique, Laura, primary, Lemos, Isadora, primary, Suñol, Mariona, primary, de Torres, Carmen, primary, Kulis, Marta, primary, Pérez-Jaume, Sara, primary, Carcaboso, Ángel M., primary, Luu, Betty, primary, Kieran, Mark W., primary, Jabado, Nada, primary, Kozlenkov, Alexey, primary, Dracheva, Stella, primary, Ramaswamy, Vijay, primary, Hovestadt, Volker, primary, Johann, Pascal, primary, Jones, David T.W., primary, Pfister, Stefan M., primary, Morales La Madrid, Andrés, primary, Cruz, Ofelia, primary, Taylor, Michael D., primary, Martin-Subero, Jose-Ignacio, primary, Mora, Jaume, primary, and Lavarino, Cinzia, primary

Published
2023
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35. Supplementary File 3 from Intratumoral Genetic and Functional Heterogeneity in Pediatric Glioblastoma

Author

Hoffman, Mary, primary, Gillmor, Aaron H., primary, Kunz, Daniel J., primary, Johnston, Michael J., primary, Nikolic, Ana, primary, Narta, Kiran, primary, Zarrei, Mehdi, primary, King, Jennifer, primary, Ellestad, Katrina, primary, Dang, Ngoc Ha, primary, Cavalli, Florence M.G., primary, Kushida, Michelle M., primary, Coutinho, Fiona J., primary, Zhu, Yuankun, primary, Luu, Betty, primary, Ma, Yussanne, primary, Mungall, Andrew J., primary, Moore, Richard, primary, Marra, Marco A., primary, Taylor, Michael D., primary, Pugh, Trevor J., primary, Dirks, Peter B., primary, Strother, Douglas, primary, Lafay-Cousin, Lucie, primary, Resnick, Adam C., primary, Scherer, Stephen, primary, Senger, Donna L., primary, Simons, Benjamin D., primary, Chan, Jennifer A., primary, Morrissy, A. Sorana, primary, and Gallo, Marco, primary

Published
2023
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38. Moving Towards Inclusive Education: Secondary School Teacher Attitudes Towards Universal Design for Learning in Australia.

Author

Hongyu Chen, Evans, David, and Luu, Betty

Subjects
TEACHER attitudes, SECONDARY school teachers, HIGH school teachers, INCLUSIVE education, UNIVERSAL design, EDUCATION of children with disabilities, STUDENTS with disabilities, CHILDREN with disabilities
Abstract

Achieving Sustainable Development Goal 4 is underpinned by the provision of quality inclusive education for all young persons, including persons with disabilities. The universal design for learning (UDL) framework provides the basis for establishing an inclusive pedagogical learning environment in classrooms. However, implementing such an inclusive pedagogical framework continues to be profoundly challenging across all countries, including Australia. Teacher attitude is the most important construct in efforts to create inclusive educational contexts. The aim of this study was to examine secondary school teachers' attitudes towards the UDL framework in Australia. One hundred and twenty mainstream secondary classroom teachers in Sydney completed an online survey. The mean values and standard deviations of a self-designed UDL framework were calculated to examine teacher attitudes. Correlations and multiple regressions were conducted to verify the relationship between teachers' attitudes and their background variables. The main results indicated that Australian secondary school teacher attitudes towards the UDL framework were generally positive, although they still had some practical concerns, such as having inflexible ideas about how to provide instructions. The findings provide useful insights for developing professional teacher training to promote inclusive education, where the UDL framework is a lens for interpreting inclusive education. [ABSTRACT FROM AUTHOR]

Published
2023
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40. Recurrence patterns across medulloblastoma subgroups: an integrated clinical and molecular analysis

Author

Ramaswamy, Vijay, Remke, Marc, Bouffet, Eric, Faria, Claudia C, Perreault, Sebastien, Cho, Yoon-Jae, Shih, David J, Luu, Betty, Dubuc, Adrian M, Northcott, Paul A, Schüller, Ulrich, Gururangan, Sridharan, McLendon, Roger, Bigner, Darell, Fouladi, Maryam, Ligon, Keith L, Pomeroy, Scott L, Dunn, Sandra, Triscott, Joanna, Jabado, Nada, Fontebasso, Adam, Jones, David T W, Kool, Marcel, Karajannis, Matthias A, Gardner, Sharon L, Zagzag, David, Nunes, Sofia, Pimentel, José, Mora, Jaume, Lipp, Eric, Walter, Andrew W, Ryzhova, Marina, Zheludkova, Olga, Kumirova, Ella, Alshami, Jad, Croul, Sidney E, Rutka, James T, Hawkins, Cynthia, Tabori, Uri, Codispoti, Kari-Elise T, Packer, Roger J, Pfister, Stefan M, Korshunov, Andrey, and Taylor, Michael D

Published
2013
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42. Fate mapping of human glioblastoma reveals an invariant stem cell hierarchy

Author

Lan, Xiaoyang, Jörg, David J., Cavalli, Florence M. G., Richards, Laura M., Nguyen, Long V., Vanner, Robert J., Guilhamon, Paul, Lee, Lilian, Kushida, Michelle M., Pellacani, Davide, Park, Nicole I., Coutinho, Fiona J., Whetstone, Heather, Selvadurai, Hayden J., Che, Clare, Luu, Betty, Carles, Annaick, Moksa, Michelle, Rastegar, Naghmeh, Head, Renee, Dolma, Sonam, Prinos, Panagiotis, Cusimano, Michael D., Das, Sunit, Bernstein, Mark, Arrowsmith, Cheryl H., Mungall, Andrew J., Moore, Richard A., Ma, Yussanne, Gallo, Marco, Lupien, Mathieu, Pugh, Trevor J., Taylor, Michael D., Hirst, Martin, Eaves, Connie J., Simons, Benjamin D., and Dirks, Peter B.

Published
2017
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43. Medulloblastoma subgroups remain stable across primary and metastatic compartments

Author

Wang, Xin, Dubuc, Adrian M., Ramaswamy, Vijay, Mack, Stephen, Gendoo, Deena M. A., Remke, Marc, Wu, Xiaochong, Garzia, Livia, Luu, Betty, Cavalli, Florence, Peacock, John, López, Borja, Skowron, Patryk, Zagzag, David, Lyden, David, Hoffman, Caitlin, Cho, Yoon-Jae, Eberhart, Charles, MacDonald, Tobey, Li, Xiao-Nan, Van Meter, Timothy, Northcott, Paul A., Haibe-Kains, Benjamin, Hawkins, Cynthia, Rutka, James T., Bouffet, Eric, Pfister, Stefan M., Korshunov, Andrey, and Taylor, Michael D.

Published
2015
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44. Telomerase inhibition abolishes the tumorigenicity of pediatric ependymoma tumor-initiating cells

Author

Barszczyk, Mark, Buczkowicz, Pawel, Castelo-Branco, Pedro, Mack, Stephen C., Ramaswamy, Vijay, Mangerel, Joshua, Agnihotri, Sameer, Remke, Marc, Golbourn, Brian, Pajovic, Sanja, Elizabeth, Cynthia, Yu, Man, Luu, Betty, Morrison, Andrew, Adamski, Jennifer, Nethery-Brokx, Kathleen, Li, Xiao-Nan, Van Meter, Timothy, Dirks, Peter B., Rutka, James T., Taylor, Michael D., Tabori, Uri, and Hawkins, Cynthia

Published
2014
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45. Activated leukocyte cell adhesion molecule expression correlates with the WNT subgroup in medulloblastoma and is involved in regulating tumor cell proliferation and invasion

Author

Achiha, Takamune, primary, Kijima, Noriyuki, additional, Kodama, Yoshinori, additional, Kagawa, Naoki, additional, Kinoshita, Manabu, additional, Fujimoto, Yasunori, additional, Nonaka, Masahiro, additional, Fukai, Junya, additional, Inoue, Akihiro, additional, Nishida, Namiko, additional, Yamanaka, Takumi, additional, Harada, Atsuko, additional, Mori, Kanji, additional, Tsuyuguchi, Naohiro, additional, Uda, Takehiro, additional, Ishibashi, Kenichi, additional, Tomogane, Yusuke, additional, Sakamoto, Daisuke, additional, Shofuda, Tomoko, additional, Yoshioka, Ema, additional, Kanematsu, Daisuke, additional, Mano, Masayuki, additional, Luu, Betty, additional, Taylor, Michael D., additional, Kanemura, Yonehiro, additional, and Kishima, Haruhiko, additional

Published
2020
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46. Metabolic Regulation of the Epigenome Drives Lethal Infantile Ependymoma

Author

Michealraj, Kulandaimanuvel Antony, primary, Kumar, Sachin A., additional, Kim, Leo J.Y., additional, Cavalli, Florence M.G., additional, Przelicki, David, additional, Wojcik, John B., additional, Delaidelli, Alberto, additional, Bajic, Andrea, additional, Saulnier, Olivier, additional, MacLeod, Graham, additional, Vellanki, Ravi N., additional, Vladoiu, Maria C., additional, Guilhamon, Paul, additional, Ong, Winnie, additional, Lee, John J.Y., additional, Jiang, Yanqing, additional, Holgado, Borja L., additional, Rasnitsyn, Alex, additional, Malik, Ahmad A., additional, Tsai, Ricky, additional, Richman, Cory M., additional, Juraschka, Kyle, additional, Haapasalo, Joonas, additional, Wang, Evan Y., additional, De Antonellis, Pasqualino, additional, Suzuki, Hiromichi, additional, Farooq, Hamza, additional, Balin, Polina, additional, Kharas, Kaitlin, additional, Van Ommeren, Randy, additional, Sirbu, Olga, additional, Rastan, Avesta, additional, Krumholtz, Stacey L., additional, Ly, Michelle, additional, Ahmadi, Moloud, additional, Deblois, Geneviève, additional, Srikanthan, Dilakshan, additional, Luu, Betty, additional, Loukides, James, additional, Wu, Xiaochong, additional, Garzia, Livia, additional, Ramaswamy, Vijay, additional, Kanshin, Evgeny, additional, Sánchez-Osuna, María, additional, El-Hamamy, Ibrahim, additional, Coutinho, Fiona J., additional, Prinos, Panagiotis, additional, Singh, Sheila, additional, Donovan, Laura K., additional, Daniels, Craig, additional, Schramek, Daniel, additional, Tyers, Mike, additional, Weiss, Samuel, additional, Stein, Lincoln D., additional, Lupien, Mathieu, additional, Wouters, Bradly G., additional, Garcia, Benjamin A., additional, Arrowsmith, Cheryl H., additional, Sorensen, Poul H., additional, Angers, Stephane, additional, Jabado, Nada, additional, Dirks, Peter B., additional, Mack, Stephen C., additional, Agnihotri, Sameer, additional, Rich, Jeremy N., additional, and Taylor, Michael D., additional

Published
2020
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47. Clinical impact of combined epigenetic and molecular analysis of pediatric low-grade gliomas

Author

Fukuoka, Kohei, primary, Mamatjan, Yasin, additional, Tatevossian, Ruth, additional, Zapotocky, Michal, additional, Ryall, Scott, additional, Stucklin, Ana Guerreiro, additional, Bennett, Julie, additional, Nobre, Liana Figueiredo, additional, Arnoldo, Anthony, additional, Luu, Betty, additional, Wen, Ji, additional, Zhu, Kaicen, additional, Leon, Alberto, additional, Torti, Dax, additional, Pugh, Trevor J, additional, Hazrati, Lili-Naz, additional, Laperriere, Normand, additional, Drake, James, additional, Rutka, James T, additional, Dirks, Peter, additional, Kulkarni, Abhaya V, additional, Taylor, Michael D, additional, Bartels, Ute, additional, Huang, Annie, additional, Zadeh, Gelareh, additional, Aldape, Kenneth, additional, Ramaswamy, Vijay, additional, Bouffet, Eric, additional, Snuderl, Matija, additional, Ellison, David, additional, Hawkins, Cynthia, additional, and Tabori, Uri, additional

Published
2020
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