891 results on '"Ng, Ho‐Keung"'
Search Results
2. Failure of human rhombic lip differentiation underlies medulloblastoma formation
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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
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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.
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- 2022
3. Development of ‘Core Outcome Sets’ for Meningioma in Clinical Studies (The COSMIC Project): protocol for two systematic literature reviews, eDelphi surveys and online consensus meetings
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Millward, Christopher P, Armstrong, Terri S, Barrington, Heather, Bell, Sabrina, Brodbelt, Andrew R, Bulbeck, Helen, Crofton, Anna, Dirven, Linda, Georgious, Theo, Grundy, Paul L, Islim, Abdurrahman I, Javadpour, Mohsen, Keshwara, Sumirat M, Koszdin, Shelli D, Marson, Anthony G, McDermott, Michael W, Meling, Torstein R, Oliver, Kathy, Plaha, Puneet, Preusser, Matthias, Santarius, Thomas, Srikandarajah, Nisaharan, Taphoorn, Martin JB, Turner, Carole, Watts, Colin, Weller, Michael, Williamson, Paula R, Zadeh, Gelareh, Najafabadi, Amir H Zamanipoor, Jenkinson, Michael D, Aldape, Kenneth, Au, Karolyn, Barnhartz-Sloan, Jill, Bi, Wenya Linda, Behling, Felix, Brastianos, Priscilla K, Brodie, Chaya, Butowski, Nicholas, Carlotti, Carlos, Castro, Ana, Cohen-Gadol, Aaron, Couce, Marta, Cusimano, Michael D, DiMeco, Francesco, Drummond, Katharine, Dunn, Ian F, Erker, Craig, Felicella, Michelle, Fountain, Daniel M, Galanis, Evanthia, Galldiks, Norbert, Giannini, Caterina, Goldbrunner, Roland, Griffith, Brent, Hashizume, Rintaro, Hanemann, C Oliver, Herold-Mende, Christel, Hnenny, Luke, Horbinski, Craig, Huang, Raymond Y, James, David, Jungk, Christine, Jungwirth, Gerhard, Kaufmann, Timothy J, Krischek, Boris, Kurz, Sylvia, Lachance, Daniel, Lafougère, Christian, Lamszus, Katrin, Lee, Ian, Liu, Jeff C, Makarenko, Serge, Malta, Tathiana, Mamatjan, Yasin, Mansouri, Alireza, Mawrin, Christian, McDermott, Michael, Moliterno-Gunel, Jennifer, Morokoff, Andrew, Munoz, David, Nassiri, Farshad, Noushmehr, Houtan, Ng, Ho-Keung, Perry, Arie, Pirouzmand, Farhad, Poisson, Laila M, Pollo, Bianca, Ragunathan, Aditya, Raleigh, David, Renovanz, Mirjam, Ricklefs, Franz, Sahm, Felix, Saladino, Andrea, Santacroce, Antonio, Schittenhelm, Jens, and Schichor, Christian
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Biomedical and Clinical Sciences ,Clinical Sciences ,Neurosciences ,Brain Disorders ,Clinical Research ,Clinical Trials and Supportive Activities ,Cancer ,Consensus ,Delphi Technique ,Humans ,Meningeal Neoplasms ,Meningioma ,Research Design ,Systematic Reviews as Topic ,Treatment Outcome ,EORTC BTG ,ICOM ,EANO ,SNO ,RANO-PRO ,BNOS ,SBNS ,BIMS ,TBTC ,International Brain Tumour Alliance ,Brainstrust ,and Brain Tumour Foundation of Canada ,clinical trial ,core outcome set ,meningioma ,Public Health and Health Services ,Other Medical and Health Sciences ,Biomedical and clinical sciences ,Health sciences ,Psychology - Abstract
IntroductionMeningioma is the most common primary intracranial tumour in adults. The majority are non-malignant, but a proportion behave more aggressively. Incidental/minimally symptomatic meningioma are often managed by serial imaging. Symptomatic meningioma, those that threaten neurovascular structures, or demonstrate radiological growth, are usually resected as first-line management strategy. For patients in poor clinical condition, or with inoperable, residual or recurrent disease, radiotherapy is often used as primary or adjuvant treatment. Effective pharmacotherapy treatments do not currently exist. There is heterogeneity in the outcomes measured and reported in meningioma clinical studies. Two 'Core Outcome Sets' (COS) will be developed: (COSMIC: Intervention) for use in meningioma clinical effectiveness trials and (COSMIC: Observation) for use in clinical studies of incidental/untreated meningioma.Methods and analysisTwo systematic literature reviews and trial registry searches will identify outcomes measured and reported in published and ongoing (1) meningioma clinical effectiveness trials, and (2) clinical studies of incidental/untreated meningioma. Outcomes include those that are clinician reported, patient reported, caregiver reported and based on objective tests (eg, neurocognitive tests), as well as measures of progression and survival. Outcomes will be deduplicated and categorised to generate two long lists. The two long lists will be prioritised through two, two-round, international, modified eDelphi surveys including patients with meningioma, healthcare professionals, researchers and those in caring/supporting roles. The two final COS will be ratified through two 1-day online consensus meetings, with representation from all stakeholder groups.Ethics and disseminationInstitutional review board (University of Liverpool) approval was obtained for the conduct of this study. Participant eConsent will be obtained prior to participation in the eDelphi surveys and consensus meetings. The two systematic literature reviews and two final COS will be published and freely available.Trial registration numberCOMET study ID 1508.
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- 2022
4. Glioneuronal tumor with ATRX alteration, kinase fusion and anaplastic features (GTAKA): a molecularly distinct brain tumor type with recurrent NTRK gene fusions
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Bogumil, Henri, Sill, Martin, Schrimpf, Daniel, Ismer, Britta, Blume, Christina, Rahmanzade, Ramin, Hinz, Felix, Cherkezov, Asan, Banan, Rouzbeh, Friedel, Dennis, Reuss, David E., Selt, Florian, Ecker, Jonas, Milde, Till, Pajtler, Kristian W., Schittenhelm, Jens, Hench, Jürgen, Frank, Stephan, Boldt, Henning B., Kristensen, Bjarne Winther, Scheie, David, Melchior, Linea C., Olesen, Viola, Sehested, Astrid, Boué, Daniel R., Abdullaev, Zied, Satgunaseelan, Laveniya, Kurth, Ina, Seidlitz, Annekatrin, White, Christine L., Ng, Ho-Keung, Shi, Zhi-Feng, Haberler, Christine, Deckert, Martina, Timmer, Marco, Goldbrunner, Roland, Tauziède-Espariat, Arnault, Varlet, Pascale, Brandner, Sebastian, Alexandrescu, Sanda, Snuderl, Matija, Aldape, Kenneth, Korshunov, Andrey, Witt, Olaf, Herold-Mende, Christel, Unterberg, Andreas, Wick, Wolfgang, Pfister, Stefan M., von Deimling, Andreas, Jones, David T. W., Sahm, Felix, and Sievers, Philipp
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- 2023
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5. The transcriptional landscape of Shh medulloblastoma.
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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
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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.
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- 2021
6. Pattern of Relapse and Treatment Response in WNT-Activated Medulloblastoma
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Nobre, Liana, Zapotocky, Michal, Khan, Sara, Fukuoka, Kohei, Fonseca, Adriana, McKeown, Tara, Sumerauer, David, Vicha, Ales, Grajkowska, Wieslawa A, Trubicka, Joanna, Li, Kay Ka Wai, Ng, Ho-Keung, Massimi, Luca, Lee, Ji Yeoun, Kim, Seung-Ki, Zelcer, Shayna, Vasiljevic, Alexandre, Faure-Conter, Cécile, Hauser, Peter, Lach, Boleslaw, van Veelen-Vincent, Marie-Lise, French, Pim J, Van Meir, Erwin G, Weiss, William A, Gupta, Nalin, Pollack, Ian F, Hamilton, Ronald L, Rao, Amulya A Nageswara, Giannini, Caterina, Rubin, Joshua B, Moore, Andrew S, Chambless, Lola B, Vibhakar, Rajeev, Ra, Young Shin, Massimino, Maura, McLendon, Roger E, Wheeler, Helen, Zollo, Massimo, Ferruci, Veronica, Kumabe, Toshihiro, Faria, Claudia C, Sterba, Jaroslav, Jung, Shin, López-Aguilar, Enrique, Mora, Jaume, Carlotti, Carlos G, Olson, James M, Leary, Sarah, Cain, Jason, Krskova, Lenka, Zamecnik, Josef, Hawkins, Cynthia E, Tabori, Uri, Huang, Annie, Bartels, Ute, Northcott, Paul A, Taylor, Michael D, Yip, Stephen, Hansford, Jordan R, Bouffet, Eric, and Ramaswamy, Vijay
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Cancer ,Clinical Research ,Evaluation of treatments and therapeutic interventions ,5.1 Pharmaceuticals ,Development of treatments and therapeutic interventions ,6.1 Pharmaceuticals ,Adolescent ,Antineoplastic Combined Chemotherapy Protocols ,Biomarkers ,Tumor ,Cerebellar Neoplasms ,Child ,Cyclophosphamide ,Female ,Humans ,Ifosfamide ,Male ,Medulloblastoma ,Middle Aged ,Neoplasm Recurrence ,Local ,Progression-Free Survival ,medulloblastoma ,WNT ,genomics ,cyclophosphamide ,chemotherapy ,prognosis ,survival - Abstract
Over the past decade, wingless-activated (WNT) medulloblastoma has been identified as a candidate for therapy de-escalation based on excellent survival; however, a paucity of relapses has precluded additional analyses of markers of relapse. To address this gap in knowledge, an international cohort of 93 molecularly confirmed WNT MB was assembled, where 5-year progression-free survival is 0.84 (95%, 0.763-0.925) with 15 relapsed individuals identified. Maintenance chemotherapy is identified as a strong predictor of relapse, with individuals receiving high doses of cyclophosphamide or ifosphamide having only one very late molecularly confirmed relapse (p = 0.032). The anatomical location of recurrence is metastatic in 12 of 15 relapses, with 8 of 12 metastatic relapses in the lateral ventricles. Maintenance chemotherapy, specifically cumulative cyclophosphamide doses, is a significant predictor of relapse across WNT MB. Future efforts to de-escalate therapy need to carefully consider not only the radiation dose but also the chemotherapy regimen and the propensity for metastatic relapses.
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- 2020
7. Longitudinal molecular trajectories of diffuse glioma in adults
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Barthel, Floris P, Johnson, Kevin C, Varn, Frederick S, Moskalik, Anzhela D, Tanner, Georgette, Kocakavuk, Emre, Anderson, Kevin J, Abiola, Olajide, Aldape, Kenneth, Alfaro, Kristin D, Alpar, Donat, Amin, Samirkumar B, Ashley, David M, Bandopadhayay, Pratiti, Barnholtz-Sloan, Jill S, Beroukhim, Rameen, Bock, Christoph, Brastianos, Priscilla K, Brat, Daniel J, Brodbelt, Andrew R, Bruns, Alexander F, Bulsara, Ketan R, Chakrabarty, Aruna, Chakravarti, Arnab, Chuang, Jeffrey H, Claus, Elizabeth B, Cochran, Elizabeth J, Connelly, Jennifer, Costello, Joseph F, Finocchiaro, Gaetano, Fletcher, Michael N, French, Pim J, Gan, Hui K, Gilbert, Mark R, Gould, Peter V, Grimmer, Matthew R, Iavarone, Antonio, Ismail, Azzam, Jenkinson, Michael D, Khasraw, Mustafa, Kim, Hoon, Kouwenhoven, Mathilde CM, LaViolette, Peter S, Li, Meihong, Lichter, Peter, Ligon, Keith L, Lowman, Allison K, Malta, Tathiane M, Mazor, Tali, McDonald, Kerrie L, Molinaro, Annette M, Nam, Do-Hyun, Nayyar, Naema, Ng, Ho Keung, Ngan, Chew Yee, Niclou, Simone P, Niers, Johanna M, Noushmehr, Houtan, Noorbakhsh, Javad, Ormond, D Ryan, Park, Chul-Kee, Poisson, Laila M, Rabadan, Raul, Radlwimmer, Bernhard, Rao, Ganesh, Reifenberger, Guido, Sa, Jason K, Schuster, Michael, Shaw, Brian L, Short, Susan C, Smitt, Peter A Sillevis, Sloan, Andrew E, Smits, Marion, Suzuki, Hiromichi, Tabatabai, Ghazaleh, Van Meir, Erwin G, Watts, Colin, Weller, Michael, Wesseling, Pieter, Westerman, Bart A, Widhalm, Georg, Woehrer, Adelheid, Yung, WK Alfred, Zadeh, Gelareh, Huse, Jason T, De Groot, John F, Stead, Lucy F, and Verhaak, Roel GW
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Neurosciences ,Brain Disorders ,Cancer ,Rare Diseases ,Brain Cancer ,Genetics ,Adult ,Chromosomes ,Human ,Pair 1 ,Chromosomes ,Human ,Pair 19 ,Disease Progression ,Glioma ,Humans ,Isocitrate Dehydrogenase ,Mutation ,Polymorphism ,Single Nucleotide ,Recurrence ,GLASS Consortium ,General Science & Technology - Abstract
The evolutionary processes that drive universal therapeutic resistance in adult patients with diffuse glioma remain unclear1,2. Here we analysed temporally separated DNA-sequencing data and matched clinical annotation from 222 adult patients with glioma. By analysing mutations and copy numbers across the three major subtypes of diffuse glioma, we found that driver genes detected at the initial stage of disease were retained at recurrence, whereas there was little evidence of recurrence-specific gene alterations. Treatment with alkylating agents resulted in a hypermutator phenotype at different rates across the glioma subtypes, and hypermutation was not associated with differences in overall survival. Acquired aneuploidy was frequently detected in recurrent gliomas and was characterized by IDH mutation but without co-deletion of chromosome arms 1p/19q, and further converged with acquired alterations in the cell cycle and poor outcomes. The clonal architecture of each tumour remained similar over time, but the presence of subclonal selection was associated with decreased survival. Finally, there were no differences in the levels of immunoediting between initial and recurrent gliomas. Collectively, our results suggest that the strongest selective pressures occur during early glioma development and that current therapies shape this evolution in a largely stochastic manner.
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- 2019
8. Antibody stabilization for thermally accelerated deep immunostaining
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Lai, Hei Ming, Tang, Yumi, Lau, Zachary Y. H., Campbell, Robert A. A., Yau, Juno C. N., Chan, Caleb C. Y., Chan, Danny C. W., Wong, Tin Yan, Wong, Harriet K. T., Yan, Leo Y. C., Wu, William K. K., Wong, Sunny H., Kwok, Ka-Wai, Wing, Yun-Kwok, Lam, Henry H. N., Ng, Ho-Keung, Mrsic-Flogel, Thomas D., Mok, Vincent C. T., Chan, Jason Y. K., and Ko, Ho
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- 2022
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9. Molecular landscape of pediatric type IDH wildtype, H3 wildtype hemispheric glioblastomas
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Hong, Liang, Shi, Zhi-Feng, Li, Kay Ka-Wai, Wang, Wei-Wei, Yang, Rui Ryan, Kwan, Johnny Sheung-Him, Chen, Hong, Li, Fang-Cheng, Liu, Xian-Zhi, Chan, Danny Tat-Ming, Li, Wen-Cai, Zhang, Zhen-Yu, Mao, Ying, and Ng, Ho-Keung
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- 2022
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10. Imaging and diagnostic advances for intracranial meningiomas.
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Huang, Raymond Y, Bi, Wenya Linda, Griffith, Brent, Kaufmann, Timothy J, la Fougère, Christian, Schmidt, Nils Ole, Tonn, Jöerg C, Vogelbaum, Michael A, Wen, Patrick Y, Aldape, Kenneth, Nassiri, Farshad, Zadeh, Gelareh, Dunn, Ian F, Au, Karolyn, Barnhartz-Sloan, Jill, Brastianos, Priscilla K, Butowski, Nicholas, Carlotti, Carlos, Cusimano, Michael D, DiMeco, Francesco, Drummond, Katharine, Galanis, Evanthia, Giannini, Caterina, Goldbrunner, Roland, Hashizume, Rintaro, Hanemann, C Oliver, Herold-Mende, Christel, Horbinski, Craig, James, David, Jenkinson, Michael D, Jungk, Christine, Kaufman, Timothy J, Krischek, Boris, Lachance, Daniel, Lafougère, Christian, Lee, Ian, Liu, Jeff C, Mamatjan, Yasin, Mansouri, Alireza, Mawrin, Christian, McDermott, Michael, Munoz, David, Noushmehr, Houtan, Ng, Ho-Keung, Perry, Arie, Pirouzmand, Farhad, Poisson, Laila M, Pollo, Bianca, Raleigh, David, Sahm, Felix, Saladino, Andrea, Santarius, Thomas, Schichor, Christian, Schultz, David, Schmidt, Nils O, Selman, Warren, Sloan, Andrew, Spears, Julian, Snyder, James, Suppiah, Suganth, Tabatabai, Ghazaleh, Tatagiba, Marcos, Tirapelli, Daniela, Tonn, Joerg C, Tsang, Derek, Deimling, Andreas von, Walbert, Tobias, Westphal, Manfred, and Workewych, Adriana M
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Rare Diseases ,Neurosciences ,Brain Disorders ,Biomedical Imaging ,Cancer ,Brain Cancer ,Humans ,Meningeal Neoplasms ,Meningioma ,Multimodal Imaging ,Neuroimaging ,International Consortium on Meningiomas ,Oncology and Carcinogenesis ,Oncology & Carcinogenesis - Abstract
The archetypal imaging characteristics of meningiomas are among the most stereotypic of all central nervous system (CNS) tumors. In the era of plain film and ventriculography, imaging was only performed if a mass was suspected, and their results were more suggestive than definitive. Following more than a century of technological development, we can now rely on imaging to non-invasively diagnose meningioma with great confidence and precisely delineate the locations of these tumors relative to their surrounding structures to inform treatment planning. Asymptomatic meningiomas may be identified and their growth monitored over time; moreover, imaging routinely serves as an essential tool to survey tumor burden at various stages during the course of treatment, thereby providing guidance on their effectiveness or the need for further intervention. Modern radiological techniques are expanding the power of imaging from tumor detection and monitoring to include extraction of biologic information from advanced analysis of radiological parameters. These contemporary approaches have led to promising attempts to predict tumor grade and, in turn, contribute prognostic data. In this supplement article, we review important current and future aspects of imaging in the diagnosis and management of meningioma, including conventional and advanced imaging techniques using CT, MRI, and nuclear medicine.
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- 2019
11. Molecular and translational advances in meningiomas
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Suppiah, Suganth, Nassiri, Farshad, Bi, Wenya Linda, Dunn, Ian F, Hanemann, Clemens Oliver, Horbinski, Craig M, Hashizume, Rintaro, James, Charles David, Mawrin, Christian, Noushmehr, Houtan, Perry, Arie, Sahm, Felix, Sloan, Andrew, Von Deimling, Andreas, Wen, Patrick Y, Aldape, Kenneth, Zadeh, Gelareh, Au, Karolyn, Barnhartz-Sloan, Jill, Brastianos, Priscilla K, Butowski, Nicholas, Carlotti, Carlos, Cusimano, Michael D, DiMeco, Francesco, Drummond, Katharine, Galanis, Evanthia, Giannini, Caterina, Goldbrunner, Roland, Griffith, Brent, Hanemann, C Oliver, Herold-Mende, Christel, Horbinski, Craig, Huang, Raymond Y, James, David, Jenkinson, Michael D, Jungk, Christine, Kaufman, Timothy J, Krischek, Boris, Lachance, Daniel, Lafougère, Christian, Lee, Ian, Liu, Jeff C, Mamatjan, Yasin, Mansouri, Alireza, McDermott, Michael, Munoz, David, Ng, Ho-Keung, Pirouzmand, Farhad, Poisson, Laila M, Pollo, Bianca, Raleigh, David, Saladino, Andrea, Santarius, Thomas, Schichor, Christian, Schultz, David, Schmidt, Nils O, Selman, Warren, Spears, Julian, Snyder, James, Tabatabai, Ghazaleh, Tatagiba, Marcos, Tirapelli, Daniela, Tonn, Joerg C, Tsang, Derek, Vogelbaum, Michael A, Deimling, Andreas von, Walbert, Tobias, Westphal, Manfred, and Workewych, Adriana M
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Brain Cancer ,Cancer ,Brain Disorders ,Rare Diseases ,Human Genome ,Genetics ,Combined Modality Therapy ,Genomics ,Humans ,Meningeal Neoplasms ,Meningioma ,Molecular Targeted Therapy ,Prognosis ,Translational Research ,Biomedical ,biomolecular ,cell lines ,epigenetic ,genetic ,sporadic meningioma ,xenograft ,International Consortium on Meningiomas ,Neurosciences ,Oncology and Carcinogenesis ,Oncology & Carcinogenesis - Abstract
Meningiomas are the most common primary intracranial neoplasm. The current World Health Organization (WHO) classification categorizes meningiomas based on histopathological features, but emerging molecular data demonstrate the importance of genomic and epigenomic factors in the clinical behavior of these tumors. Treatment options for symptomatic meningiomas are limited to surgical resection where possible and adjuvant radiation therapy for tumors with concerning histopathological features or recurrent disease. At present, alternative adjuvant treatment options are not available in part due to limited historical biological analysis and clinical trial investigation on meningiomas. With advances in molecular and genomic techniques in the last decade, we have witnessed a surge of interest in understanding the genomic and epigenomic landscape of meningiomas. The field is now at the stage to adopt this molecular knowledge to refine meningioma classification and introduce molecular algorithms that can guide prediction and therapeutics for this tumor type. Animal models that recapitulate meningiomas faithfully are in critical need to test new therapeutics to facilitate rapid-cycle translation to clinical trials. Here we review the most up-to-date knowledge of molecular alterations that provide insight into meningioma behavior and are ready for application to clinical trial investigation, and highlight the landscape of available preclinical models in meningiomas.
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- 2019
12. Glioma through the looking GLASS: molecular evolution of diffuse gliomas and the Glioma Longitudinal Analysis Consortium
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Aldape, Kenneth, Amin, Samirkumar B, Ashley, David M, Barnholtz-Sloan, Jill S, Bates, Amanda J, Beroukhim, Rameen, Bock, Christoph, Brat, Daniel J, Claus, Elizabeth B, Costello, Joseph F, de Groot, John F, Finocchiaro, Gaetano, French, Pim J, Gan, Hui K, Griffith, Brent, Herold-Mende, Christel C, Horbinski, Craig, Iavarone, Antonio, Kalkanis, Steven N, Karabatsou, Konstantina, Kim, Hoon, Kouwenhoven, Mathilde CM, McDonald, Kerrie L, Miletic, Hrvoje, Nam, Do-Hyun, Ng, Ho Keung, Niclou, Simone P, Noushmehr, Houtan, Ormond, D Ryan, Poisson, Laila M, Reifenberger, Guido, Roncaroli, Federico, Sa, Jason K, Smitt, Peter AE Sillevis, Smits, Marion, Souza, Camila F, Tabatabai, Ghazaleh, Van Meir, Erwin G, Verhaak, Roel GW, Watts, Colin, Wesseling, Pieter, Woehrer, Adelheid, Yung, WK Alfred, Jungk, Christine, Hau, Ann-Christin, van Dyck, Eric, Westerman, Bart A, Yin, Julia, Abiola, Olajide, Zeps, Nikolaj, Grimmond, Sean, Buckland, Michael, Khasraw, Mustafa, Sulman, Erik P, Muscat, Andrea M, and Stead, Lucy
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Cancer ,Human Genome ,Brain Cancer ,Rare Diseases ,Orphan Drug ,Brain Disorders ,Neurosciences ,Genetics ,Brain Neoplasms ,Evolution ,Molecular ,Genomics ,Glioma ,Humans ,Longitudinal Studies ,characterization ,evolution ,glioma ,sequencing ,subtypes ,GLASS Consortium ,Oncology and Carcinogenesis ,Oncology & Carcinogenesis - Abstract
Adult diffuse gliomas are a diverse group of brain neoplasms that inflict a high emotional toll on patients and their families. The Cancer Genome Atlas and similar projects have provided a comprehensive understanding of the somatic alterations and molecular subtypes of glioma at diagnosis. However, gliomas undergo significant cellular and molecular evolution during disease progression. We review the current knowledge on the genomic and epigenetic abnormalities in primary tumors and after disease recurrence, highlight the gaps in the literature, and elaborate on the need for a new multi-institutional effort to bridge these knowledge gaps and how the Glioma Longitudinal Analysis Consortium (GLASS) aims to systemically catalog the longitudinal changes in gliomas. The GLASS initiative will provide essential insights into the evolution of glioma toward a lethal phenotype, with the potential to reveal targetable vulnerabilities and, ultimately, improved outcomes for a patient population in need.
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- 2018
13. Spectrum and prevalence of genetic predisposition in medulloblastoma: a retrospective genetic study and prospective validation in a clinical trial cohort.
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Waszak, Sebastian M, Northcott, Paul A, Buchhalter, Ivo, Robinson, Giles W, Sutter, Christian, Groebner, Susanne, Grund, Kerstin B, Brugières, Laurence, Jones, David TW, Pajtler, Kristian W, Morrissy, A Sorana, Kool, Marcel, Sturm, Dominik, Chavez, Lukas, Ernst, Aurelie, Brabetz, Sebastian, Hain, Michael, Zichner, Thomas, Segura-Wang, Maia, Weischenfeldt, Joachim, Rausch, Tobias, Mardin, Balca R, Zhou, Xin, Baciu, Cristina, Lawerenz, Christian, Chan, Jennifer A, Varlet, Pascale, Guerrini-Rousseau, Lea, Fults, Daniel W, Grajkowska, Wiesława, Hauser, Peter, Jabado, Nada, Ra, Young-Shin, Zitterbart, Karel, Shringarpure, Suyash S, De La Vega, Francisco M, Bustamante, Carlos D, Ng, Ho-Keung, Perry, Arie, MacDonald, Tobey J, Hernáiz Driever, Pablo, Bendel, Anne E, Bowers, Daniel C, McCowage, Geoffrey, Chintagumpala, Murali M, Cohn, Richard, Hassall, Timothy, Fleischhack, Gudrun, Eggen, Tone, Wesenberg, Finn, Feychting, Maria, Lannering, Birgitta, Schüz, Joachim, Johansen, Christoffer, Andersen, Tina V, Röösli, Martin, Kuehni, Claudia E, Grotzer, Michael, Kjaerheim, Kristina, Monoranu, Camelia M, Archer, Tenley C, Duke, Elizabeth, Pomeroy, Scott L, Shelagh, Redmond, Frank, Stephan, Sumerauer, David, Scheurlen, Wolfram, Ryzhova, Marina V, Milde, Till, Kratz, Christian P, Samuel, David, Zhang, Jinghui, Solomon, David A, Marra, Marco, Eils, Roland, Bartram, Claus R, von Hoff, Katja, Rutkowski, Stefan, Ramaswamy, Vijay, Gilbertson, Richard J, Korshunov, Andrey, Taylor, Michael D, Lichter, Peter, Malkin, David, Gajjar, Amar, Korbel, Jan O, and Pfister, Stefan M
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Humans ,Medulloblastoma ,Cerebellar Neoplasms ,Genetic Predisposition to Disease ,Risk Factors ,Retrospective Studies ,Prospective Studies ,Reproducibility of Results ,Predictive Value of Tests ,Gene Expression Profiling ,Pedigree ,DNA Mutational Analysis ,DNA Methylation ,Heredity ,Phenotype ,Germ-Line Mutation ,Models ,Genetic ,Adolescent ,Adult ,Child ,Child ,Preschool ,Infant ,Female ,Male ,Young Adult ,Genetic Testing ,Transcriptome ,Biomarkers ,Tumor ,Progression-Free Survival ,Exome Sequencing ,Brain Cancer ,Genetics ,Cancer ,Human Genome ,Pediatric ,Pediatric Cancer ,Rare Diseases ,Brain Disorders ,Aetiology ,2.1 Biological and endogenous factors ,Oncology and Carcinogenesis ,Oncology & Carcinogenesis - Abstract
BackgroundMedulloblastoma is associated with rare hereditary cancer predisposition syndromes; however, consensus medulloblastoma predisposition genes have not been defined and screening guidelines for genetic counselling and testing for paediatric patients are not available. We aimed to assess and define these genes to provide evidence for future screening guidelines.MethodsIn this international, multicentre study, we analysed patients with medulloblastoma from retrospective cohorts (International Cancer Genome Consortium [ICGC] PedBrain, Medulloblastoma Advanced Genomics International Consortium [MAGIC], and the CEFALO series) and from prospective cohorts from four clinical studies (SJMB03, SJMB12, SJYC07, and I-HIT-MED). Whole-genome sequences and exome sequences from blood and tumour samples were analysed for rare damaging germline mutations in cancer predisposition genes. DNA methylation profiling was done to determine consensus molecular subgroups: WNT (MBWNT), SHH (MBSHH), group 3 (MBGroup3), and group 4 (MBGroup4). Medulloblastoma predisposition genes were predicted on the basis of rare variant burden tests against controls without a cancer diagnosis from the Exome Aggregation Consortium (ExAC). Previously defined somatic mutational signatures were used to further classify medulloblastoma genomes into two groups, a clock-like group (signatures 1 and 5) and a homologous recombination repair deficiency-like group (signatures 3 and 8), and chromothripsis was investigated using previously established criteria. Progression-free survival and overall survival were modelled for patients with a genetic predisposition to medulloblastoma.FindingsWe included a total of 1022 patients with medulloblastoma from the retrospective cohorts (n=673) and the four prospective studies (n=349), from whom blood samples (n=1022) and tumour samples (n=800) were analysed for germline mutations in 110 cancer predisposition genes. In our rare variant burden analysis, we compared these against 53 105 sequenced controls from ExAC and identified APC, BRCA2, PALB2, PTCH1, SUFU, and TP53 as consensus medulloblastoma predisposition genes according to our rare variant burden analysis and estimated that germline mutations accounted for 6% of medulloblastoma diagnoses in the retrospective cohort. The prevalence of genetic predispositions differed between molecular subgroups in the retrospective cohort and was highest for patients in the MBSHH subgroup (20% in the retrospective cohort). These estimates were replicated in the prospective clinical cohort (germline mutations accounted for 5% of medulloblastoma diagnoses, with the highest prevalence [14%] in the MBSHH subgroup). Patients with germline APC mutations developed MBWNT and accounted for most (five [71%] of seven) cases of MBWNT that had no somatic CTNNB1 exon 3 mutations. Patients with germline mutations in SUFU and PTCH1 mostly developed infant MBSHH. Germline TP53 mutations presented only in childhood patients in the MBSHH subgroup and explained more than half (eight [57%] of 14) of all chromothripsis events in this subgroup. Germline mutations in PALB2 and BRCA2 were observed across the MBSHH, MBGroup3, and MBGroup4 molecular subgroups and were associated with mutational signatures typical of homologous recombination repair deficiency. In patients with a genetic predisposition to medulloblastoma, 5-year progression-free survival was 52% (95% CI 40-69) and 5-year overall survival was 65% (95% CI 52-81); these survival estimates differed significantly across patients with germline mutations in different medulloblastoma predisposition genes.InterpretationGenetic counselling and testing should be used as a standard-of-care procedure in patients with MBWNT and MBSHH because these patients have the highest prevalence of damaging germline mutations in known cancer predisposition genes. We propose criteria for routine genetic screening for patients with medulloblastoma based on clinical and molecular tumour characteristics.FundingGerman Cancer Aid; German Federal Ministry of Education and Research; German Childhood Cancer Foundation (Deutsche Kinderkrebsstiftung); European Research Council; National Institutes of Health; Canadian Institutes for Health Research; German Cancer Research Center; St Jude Comprehensive Cancer Center; American Lebanese Syrian Associated Charities; Swiss National Science Foundation; European Molecular Biology Organization; Cancer Research UK; Hertie Foundation; Alexander and Margaret Stewart Trust; V Foundation for Cancer Research; Sontag Foundation; Musicians Against Childhood Cancer; BC Cancer Foundation; Swedish Council for Health, Working Life and Welfare; Swedish Research Council; Swedish Cancer Society; the Swedish Radiation Protection Authority; Danish Strategic Research Council; Swiss Federal Office of Public Health; Swiss Research Foundation on Mobile Communication; Masaryk University; Ministry of Health of the Czech Republic; Research Council of Norway; Genome Canada; Genome BC; Terry Fox Research Institute; Ontario Institute for Cancer Research; Pediatric Oncology Group of Ontario; The Family of Kathleen Lorette and the Clark H Smith Brain Tumour Centre; Montreal Children's Hospital Foundation; The Hospital for Sick Children: Sonia and Arthur Labatt Brain Tumour Research Centre, Chief of Research Fund, Cancer Genetics Program, Garron Family Cancer Centre, MDT's Garron Family Endowment; BC Childhood Cancer Parents Association; Cure Search Foundation; Pediatric Brain Tumor Foundation; Brainchild; and the Government of Ontario.
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- 2018
14. Establishment and characterization of meningioma patient-derived organoid
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Chan, Henry Siu Cheung, Ng, Ho Keung, Chan, Aden Ka-Yin, Cheng, Sau Ha, Chow, Chit, Wong, Nathalie, and Wong, George Kwok Chu
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- 2021
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15. Expanding the clinical and molecular spectrum of pituitary blastoma
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Liu, Anthony Pak-Yin, Li, Kay Ka-Wai, Chow, Chit, Chan, Shing, Leung, Alex Wing-Kwan, Shing, Matthew Ming-Kong, To, Ka-Fai, Chan, Danny Tat-Ming, Chan, Godfrey Chi-Fung, and Ng, Ho-Keung
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- 2022
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16. Mismatch repair proteins PMS2 and MLH1 can further refine molecular stratification of IDH-mutant lower grade astrocytomas
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Yang, Rui Ryan, Li, Kay Ka-Wai, Zhang, Zhen-Yu, Chan, Aden Ka-Yin, Wang, Wei-Wei, Chan, Danny Tat-Ming, Li, Wen-Cai, Liu, Xian-Zhi, Li, Fang-Cheng, Chen, Hong, Ng, Ho-Keung, Mao, Ying, and Shi, Zhi-Feng
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- 2021
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17. Molecular landscape of IDH-mutant primary astrocytoma Grade IV/glioblastomas
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Wong, Queenie Hoi-Wing, Li, Kay Ka-Wai, Wang, Wei-Wei, Malta, Tathiane M., Noushmehr, Houtan, Grabovska, Yura, Jones, Chris, Chan, Aden Ka-Yin, Kwan, Johnny Sheung-Him, Huang, Queenie Jun-Qi, Wong, Gabriel Chun-Hei, Li, Wen-Cai, Liu, Xian-Zhi, Chen, Hong, Chan, Danny Tat-Ming, Mao, Ying, Zhang, Zhen-Yu, Shi, Zhi-Feng, and Ng, Ho-Keung
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- 2021
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18. Intertumoral Heterogeneity within Medulloblastoma Subgroups
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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
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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.
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- 2017
19. Histological Characteristics of Intracranial Atherosclerosis in a Chinese Population: A Postmortem Study
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Yang, Wen Jie, Fisher, Mark, Zheng, Lu, Niu, Chun Bo, Paganini-Hill, Annlia, Zhao, Hai Lu, Xu, Yun, Wong, Ka Sing, Ng, Ho Keung, and Chen, Xiang Yan
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Brain Disorders ,Cardiovascular ,Atherosclerosis ,Stroke ,Aging ,Neurosciences ,intracranial atherosclerosis ,pathology ,anterior circulation ,posterior circulation ,intraplaque hemorrhage ,thrombus ,Anterior circulation ,Intracranial atherosclerosis ,Intraplaque hemorrhage ,Pathology ,Posterior circulation ,Thrombus ,adult ,aged ,Article ,atherosclerotic plaque ,autopsy ,basilar artery ,brain atherosclerosis ,brain calcification ,brain hemorrhage ,Chinese ,clinical article ,disease severity ,female ,histopathology ,human ,human tissue ,immunohistochemistry ,macrophage migration ,male ,middle aged ,middle cerebral artery ,neovascularization ,occlusive cerebrovascular disease ,vertebral artery ,Clinical Sciences ,Psychology - Abstract
BackgroundAnterior and posterior circulation atherosclerosis differ in vascular risk factors and stroke mechanisms. However, few studies have compared the pathological features between these lesions. Using a series of intracranial artery specimens, we characterized the intracranial atherosclerotic lesions and compared pathological features among different arteries of the intracranial vasculature.MethodsIntracranial large arteries of 32 consecutively recruited autopsy cases of Chinese adults aged 45 years or older were examined pathologically using routine histology and immunostaining, to characterize the pathological features of the atherosclerotic lesions. We analyzed middle cerebral arteries (MCAs) (both left and right), vertebral arteries (VAs) (side more affected), and basilar arteries (BAs).ResultsProgressive atherosclerotic lesions were present in 91(71%) of the 128 arteries examined. Features of complicated plaques were infrequently detected: plaque hemorrhage was encountered in 12%, neovasculature in 12%, lumen thrombi in 13%, macrophage infiltration in 20%, and calcification in 25% of arteries. Luminal narrowing of MCA was the most severe, followed by VA; the BA least stenotic (37 ± 25 vs. 30 ± 24 vs. 20 ± 20%, all p
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- 2017
20. Clinical and molecular heterogeneity of pineal parenchymal tumors: a consensus study
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Liu, Anthony P. Y., Li, Bryan K., Pfaff, Elke, Gudenas, Brian, Vasiljevic, Alexandre, Orr, Brent A., Dufour, Christelle, Snuderl, Matija, Karajannis, Matthias A., Rosenblum, Marc K., Hwang, Eugene I., Ng, Ho-Keung, Hansford, Jordan R., Szathmari, Alexandru, Faure-Conter, Cécile, Merchant, Thomas E., Levine, Max, Bouvier, Nancy, von Hoff, Katja, Mynarek, Martin, Rutkowski, Stefan, Sahm, Felix, Kool, Marcel, Hawkins, Cynthia, Onar-Thomas, Arzu, Robinson, Giles W., Gajjar, Amar, Pfister, Stefan M., Bouffet, Eric, Northcott, Paul A., Jones, David T. W., and Huang, Annie
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- 2021
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21. Integrated (epi)-Genomic Analyses Identify Subgroup-Specific Therapeutic Targets in CNS Rhabdoid Tumors
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Torchia, Jonathon, Golbourn, Brian, Feng, Shengrui, Ho, Ching, Sin-Chan, Patrick, Vasiljevic, Alexandre, Norman, Joseph D, Guilhamon, Paul, Garzia, Livia, Agamez, Natalia R, Lu, Mei, Chan, Tiffany S, Picard, Daniel, de Antonellis, Pasqualino, Khuong-Quang, Dong-Anh, Planello, Aline C, Zeller, Constanze, Barsyte-Lovejoy, Dalia, Lafay-Cousin, Lucie, Letourneau, Louis, Bourgey, Mathieu, Yu, Man, Gendoo, Deena MA, Dzamba, Misko, Barszczyk, Mark, Medina, Tiago, Riemenschneider, Alexandra N, Morrissy, A Sorana, Ra, Young-Shin, Ramaswamy, Vijay, Remke, Marc, Dunham, Christopher P, Yip, Stephen, Ng, Ho-keung, Lu, Jian-Qiang, Mehta, Vivek, Albrecht, Steffen, Pimentel, Jose, Chan, Jennifer A, Somers, Gino R, Faria, Claudia C, Roque, Lucia, Fouladi, Maryam, Hoffman, Lindsey M, Moore, Andrew S, Wang, Yin, Choi, Seung Ah, Hansford, Jordan R, Catchpoole, Daniel, Birks, Diane K, Foreman, Nicholas K, Strother, Doug, Klekner, Almos, Bognár, Laszló, Garami, Miklós, Hauser, Péter, Hortobágyi, Tibor, Wilson, Beverly, Hukin, Juliette, Carret, Anne-Sophie, Van Meter, Timothy E, Hwang, Eugene I, Gajjar, Amar, Chiou, Shih-Hwa, Nakamura, Hideo, Toledano, Helen, Fried, Iris, Fults, Daniel, Wataya, Takafumi, Fryer, Chris, Eisenstat, David D, Scheinemann, Katrin, Fleming, Adam J, Johnston, Donna L, Michaud, Jean, Zelcer, Shayna, Hammond, Robert, Afzal, Samina, Ramsay, David A, Sirachainan, Nongnuch, Hongeng, Suradej, Larbcharoensub, Noppadol, Grundy, Richard G, Lulla, Rishi R, Fangusaro, Jason R, Druker, Harriet, Bartels, Ute, Grant, Ronald, Malkin, David, McGlade, C Jane, Nicolaides, Theodore, Tihan, Tarik, Phillips, Joanna, Majewski, Jacek, Montpetit, Alexandre, Bourque, Guillaume, Bader, Gary D, Reddy, Alyssa T, Gillespie, G Yancey, and Warmuth-Metz, Monika
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Genetics ,Human Genome ,Rare Diseases ,Orphan Drug ,Cancer ,2.1 Biological and endogenous factors ,Development of treatments and therapeutic interventions ,Aetiology ,5.1 Pharmaceuticals ,Cell Line ,Tumor ,Cell Proliferation ,Cell Survival ,Central Nervous System Neoplasms ,Chromatin ,DNA Methylation ,Dasatinib ,Epigenesis ,Genetic ,Epigenomics ,Humans ,Mutation ,Protein Kinase Inhibitors ,Pyrimidines ,Receptor ,Platelet-Derived Growth Factor beta ,Rhabdoid Tumor ,SMARCB1 Protein ,Teratoma ,ATRT ,enhancer ,epigenomics ,genomics ,rhabdoid tumors ,subgroup-specific therapeutics ,Neurosciences ,Oncology and Carcinogenesis ,Oncology & Carcinogenesis - Abstract
We recently reported that atypical teratoid rhabdoid tumors (ATRTs) comprise at least two transcriptional subtypes with different clinical outcomes; however, the mechanisms underlying therapeutic heterogeneity remained unclear. In this study, we analyzed 191 primary ATRTs and 10 ATRT cell lines to define the genomic and epigenomic landscape of ATRTs and identify subgroup-specific therapeutic targets. We found ATRTs segregated into three epigenetic subgroups with distinct genomic profiles, SMARCB1 genotypes, and chromatin landscape that correlated with differential cellular responses to a panel of signaling and epigenetic inhibitors. Significantly, we discovered that differential methylation of a PDGFRB-associated enhancer confers specific sensitivity of group 2 ATRT cells to dasatinib and nilotinib, and suggest that these are promising therapies for this highly lethal ATRT subtype.
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- 2016
22. The Molecular Landscape of Primary CNS Lymphomas (PCNSLs) in Children and Young Adults.
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Shi, Zhi-Feng, Li, Kay Ka-Wai, Liu, Anthony Pak-Yin, Chung, Nellie Yuk-Fei, Wong, Sze-Ching, Chen, Hong, Woo, Peter Yat-Ming, Chan, Danny Tat-Ming, Mao, Ying, and Ng, Ho-Keung
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GENE rearrangement ,LYMPHOMAS ,SYMPTOMS ,AGE distribution ,DESCRIPTIVE statistics ,CENTRAL nervous system tumors ,GENE expression ,GENE expression profiling ,FLUORESCENCE in situ hybridization ,GENETIC mutation ,PHENOTYPES ,HLA-B27 antigen ,IMMUNOMODULATORS ,SEQUENCE analysis ,CHILDREN ,ADULTS - Abstract
Simple Summary: Primary CNS lymphomas (PCNSLs) in children and young adults are not common. In this study, we studied immunophenotype, gene rearrangement, homozygous deletion of CDKN2A and HLA, and mutation profiling of 34 PCNSL patients aged between 7 and 39 years and correlated the findings with clinical features and outcome. We found that the PCNSLs of the pediatric and young adult patients were immunophenotypically different from the PCNSLs of the older patients. They were also molecularly different from the latter group, as many of the common molecular findings identified in the latter were not present or common in the PCNSLs of the pediatric and young adult patients. Pediatric brain tumors are often noted to be different from their adult counterparts in terms of molecular features. Primary CNS lymphomas (PCNSLs) are mostly found in elderly adults and are uncommon in children and teenagers. There has only been scanty information about the molecular features of PCNSLs at a young age. We examined PCNSLs in 34 young patients aged between 7 and 39 years for gene rearrangements of BCl2, BCL6, CCND1, IRF4, IGH, IGL, IGK, and MYC, homozygous deletions (HD) of CDKN2A, and HLA by FISH. Sequencing was performed using WES, panel target sequencing, or Sanger sequencing due to the small amount of available tissues. The median OS was 97.5 months and longer than that for older patients with PCNSLs. Overall, only 14 instances of gene rearrangement were found (5%), and patients with any gene rearrangement were significantly older (p = 0.029). CDKN2A HD was associated with a shorter OS (p < 0.001). Only 10/31 (32%) showed MYD88 mutations, which were not prognostically significant, and only three of them were L265P mutations. CARD11 mutations were found in 8/24 (33%) cases only. Immunophenotypically, the cases were predominantly GCB, in contrast to older adults (61%). In summary, we showed that molecular findings identified in the PCNSLs of the older patients were only sparingly present in pediatric and young adult patients. [ABSTRACT FROM AUTHOR]
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- 2024
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23. Author Correction: Failure of human rhombic lip differentiation underlies medulloblastoma formation
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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.
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- 2022
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24. Rare Pediatric Cerebellar High-Grade Gliomas Mimic Medulloblastomas Histologically and Transcriptomically and Show p53 Mutations
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Shi, Zhi-Feng, primary, Li, Kay Ka-Wai, additional, Liu, Anthony Pak-Yin, additional, Chung, Nellie Yuk-Fei, additional, Chow, Chit, additional, Chen, Hong, additional, Kan, Nim-Chi Amanda, additional, Zhu, Xian-Lun, additional, Chan, Danny Tat-Ming, additional, Mao, Ying, additional, and Ng, Ho-Keung, additional
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- 2024
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25. Alternative lengthening of telomeres is seen in a proportion of oligodendrogliomas and is associated with a worse prognosis
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Shi, Zhi-Feng, primary, Li, Kay Ka-Wai, additional, Chan, Danny Tat-Ming, additional, Mao, Ying, additional, and Ng, Ho-Keung, additional
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- 2024
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26. Prognostic value of medulloblastoma extent of resection after accounting for molecular subgroup: a retrospective integrated clinical and molecular analysis
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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
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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.
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- 2016
27. BIOM-02. CSF LIQUID-BASED DIAGNOSIS OF LEPTOMENINGEAL DISEASE (LMD) FROM NON-SMALL CELL LUNG CANCER (NSCLC) USING DDPCR AGAINST EGFR MUTATIONS
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Li, Kay Ka-Wai, primary, Fung, Jackie Mei-Wah, additional, Woo, Peter Yat-Ming, additional, Liu, Anthony Pak-Yin, additional, Chow, Chit, additional, and Ng, Ho-Keung, additional
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- 2023
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28. PATH-20. IDH MUTANT ASTROCYTOMAS WITHOUT RECEIVING ADJUVANT TREATMENT DO NOT DEVELOP HYPERMUTATION OR SPECIFIC GENE MUTATION AND MYC, CDKN2A AND PDGFRA ARE INVOLVED IN MALIGNANT TRANSFORMATION
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Li, Kay Ka-Wai, primary, Shi, Zhi-Feng, additional, Kwan, Johnny Sheung-Him, additional, Chan, Danny Tat-Ming, additional, and Ng, Ho-Keung, additional
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- 2023
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29. Rapid diagnosis of IDH1-mutated gliomas by 2-HG detection with gas chromatography mass spectrometry
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Xu, Hao, Xia, Yu-Kun, Li, Chun-Jie, Zhang, Jin-Ye, Liu, Ying, Yi, Wei, Qin, Zhi-Yong, Chen, Liang, Shi, Zhi-Feng, Quan, Kai, Yang, Zi-Xiao, Guan, Kun-Liang, Xiong, Yue, Ng, Ho-Keung, Ye, Dan, Hua, Wei, and Mao, Ying
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- 2019
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30. International Society Of Neuropathology--Haarlem consensus guidelines for nervous system tumor classification and grading.
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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
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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.
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- 2014
31. ISN‐Haarlem Brain Tumor Classification Guidelines
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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
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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.
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- 2014
32. MEDULLOBLASTOMA
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Morfouace, Marie, Shelat, Anang, Megan, Jacus, Freeman, Burgess B, Robinson, Sarah, Throm, Stacy, Olson, James M, Li, Xiao-Nan, Guy, Kip R, Robinson, Giles, Stewart, Clinton, Gajjar, Amar, Roussel, Martine, Sirachainan, Nongnuch, Pakakasama, Samart, Anurathapan, Usanarat, Hansasuta, Ake, Dhanachai, Mantana, Khongkhatithum, Chaiyos, Hongeng, Suradej, Feroze, Abdullah, Lee, Kyu-Sun, Gholamin, Sharareh, Wu, Zhihao, Lu, Bingwei, Mitra, Siddhartha, Cheshier, Samuel, Northcott, Paul, Lee, Catherine, Zichner, Thomas, Lichter, Peter, Korbel, Jan, Wechsler-Reya, Robert, Pfister, Stefan, Project, ICGC PedBrain Tumor, Li, Kay Ka-Wai, Xia, Tian, Ma, Fanny Man Ting, Zhang, Rong, Zhou, Liangfu, Lau, Kin-Mang, Ng, Ho-Keung, Lafay-Cousin, Lucie, Chi, Susan, Madden, Jennifer, Smith, Amy, Wells, Elisabeth, Owens, Emily, Strother, Douglas, Foreman, Nicholas, Packer, Roger, Bouffet, Eric, Wataya, Takafumi, Peacock, John, Taylor, Michael D, Ivanov, Delyan, Garnett, Martin, Parker, Terry, Alexander, Cameron, Meijer, Lisethe, Grundy, Richard, Gellert, Paul, Ashford, Marianne, Walker, David, Hayase, Tomomi, Kawahara, Yuta, Yagi, Masaki, Minami, Takaomi, Kanai, Nobuyuki, Yamaguchi, Takehiko, Gomi, Akira, Morimoto, Akira, Hill, Rebecca, Kuijper, Sanne, Lindsey, Janet, Schwalbe, Ed, Barker, Karen, Boult, Jessica, Williamson, Daniel, Ahmad, Zai, Hallsworth, Albert, Ryan, Sarra, Poon, Evon, Robinson, Simon, Ruddle, Ruth, Raynaud, Florence, Howell, Louise, Kwok, Colin, Joshi, Abhijit, Nicholson, Sarah Leigh, Crosier, Stephen, Wharton, Stephen, Robson, Keith, Michalski, Antony, Hargrave, Darren, Jacques, Thomas, Pizer, Barry, Bailey, Simon, Swartling, Fredrik, and Petrie, Kevin
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Neurosciences ,Oncology and Carcinogenesis ,Oncology & Carcinogenesis - Abstract
BACKGROUND: LMD in children with recurrent medulloblastoma and other PNETs carries a poor prognosis and novel therapies are urgently needed to improve disease control. Somatostatin receptor-2 (SSR-2)is overexpressed in medulloblastoma and other central PNETs and can serve as a target for radionuclide tagged somatostatin analogues like 177Lu-DOTA-TATE that has shown considerable efficacy in adults with SSR-2 positive neuro-endocrine tumors. As a preliminary step prior to testing this agent in children with LMD, we performed an efficacy study of i.t. 177Lu-DOTA-TATE in athymic rats bearing LMD from MBL. METHODS: The subarachnoid space was accessed through the animal's cervical spine and a catheter was threaded along the dorsal aspect of spinal cord to the lumbar region and injected with 1 x 107 D341 human MBL cells and treatment initiated 3 days later. Groups of 10 animals received a single i.t. dose of 2, 3, or 5 mCi of 177Lu- DOTA-TATE or saline control. Animals were followed 300 days for survival. RESULTS: Treatment with 2 mCi resulted in an increase in median survival of 58.3% compared with saline control (p < 0.001). Treatment with 5.0 mCi of 177Lu-DOTA-TATE increased median survival by 75.0% compared with the saline control group while a single dose of 3.0 mCi 177Lu-DOTA-TATE increased median survival compared with saline controls by 519.4%. Long-term survivors were seen in 0 of 10 animals treated with saline, 4 of 11 treated with 3 mCi, and 3 of 12 treated with 5.0 mCi. CONCLUSION: Intrathecal 177Lu- DOTA TATE is efficacious in controlling LMD from medulloblastoma in athymic rats. A phase I trial of this agent is being planned in children with LMD from recurrent MBL and other CNS PNETs. INTRODUCTION: Medulloblastoma/PNET is the most common malignant brain tumor in children. For children older than 3 years, the treatment of high risk group includes surgery, craniospinal (CSI) radiation therapy (30-36 Gy) plus local boost radiotherapy (54-56 Gy) and adjuvant chemotherapy, such as cisplatinum, carboplatin, lomustine, cyclophosphamide, and vincristine. The results have demonstrated 5-year overall survival (OS) of 40-60%. This study aimed to evaluate the outcomes of high risk medulloblastoma/PNET patients who were treated with radiation and adjuvant chemotherapy. METHODS: Patients were diagnosed with high risk medulloblastoma/PNET according to the histopathology, medulloblastoma risk classification by an evidence of metastasis or the residual tumor more than 1.5 cm2 and evidence of residual tumor after surgery in PNET. Treatment protocol was CSI RT 36 Gy with local boost at tumor 54-56 Gy. Two to four weeks after RT, patients received 8 courses of chemotherapy consisting of cyclophosphamide 800 mg/m2, day 1-3 and vincristine 2 mg/m2, week 1-3, alternated with carboplatin 200 mg/m2, day 1-3 and etoposide 150 mg/m2, day 1-3. RESULTS: Total of 25 patients, male: female of 2.6:1 and mean ± SD for age of 9.7± 3.0 years, were enrolled. The 5-year progression free survival and OS were 41.6± 11.7% and 61.5± 12.9%,respectively. The age and sex did not determine the difference in outcomes. The hematotoxic side effect, according to the National Cancer Institute's Common Terminology Criteria, were grade 4 leucopenia 60%, grade 4 neutropenia 60%, grade 4 anemia 20%, grade 4 thrombocytopenia 16%, grade 3 leucopenia 20%, grade 3 neutropenia 20%, grade 3 anemia 40%, and grade 3 thrombocytopenia 36%. Febrile neutropenia was found in 11 patients (44%). CONCLUSION: The present study demonstrated the similar outcomes of high risk medulloblastoma/PNET with the previous studies. Although, the grade 3 and 4 hematologic toxicity was high, no treatment related death was found. OBJECTIVE: Recent investigations revealed an association between transcriptional subtypes and morphological features in medulloblastoma. Since both characteristics are of prognostic significance, a precise correlation between them should be well established. Therefore we re-examined paediatric nodular medulloblastoma tumours for correlation with molecular subtypes of disease. METHODS: Paediatric patients with previously diagnosed desmoplastic/nodular (D/N) or medulloblastoma with extensive nodularity (MBEN) histopathology were re-analysed by two neuropathologists. In addition to H&E-stained slides, reticulin preparations were simultaneously analysed from the same FFPE blocks. For identification of transcriptional subtypes of tumours immunohistopathological analyses were performed using a panel of representative antibodies. MYCC amplification was detected by FISH. RESULTS: Altogether 28 tumours with original MBEN or D/N diagnosis where molecular subtypes could be determined were identified. All tumours with MBEN histology belonged to SHH group and displayed distinctive reticulin-positive internodular reaction. However, only ∼60% of tumours with original D/N diagnosis were reticulin-positive. They belonged to SHH type, were mainly infantile and patients are still alive. Among reticulin-negative tumours only two were of the SHH type and were subsequently reclassified as classic and anaplastic tumours with pseudonodules. Importantly, all remaining reticulin-negative tumours with a presence of nodules in H&E staining belonged to the non-WNT,SHH type. Therefore the original diagnosis was again reclassified as classic or anaplastic tumours with pseudonodules. Patients from this group were only males, with median age 14 years old, one had MYCC amplification and two of them died because of disease. Therefore, non-WNT,SHH tumours did not display typical desmoplastic/nodular histology accompanied by reticulin positive reaction as opposite to truly D/N tumours being typical for SHH molecular group (p < 0.001). CONCLUSION: Reticulin staining is necessary to distinguish two different biologically and clinically group of nodular tumours which appear morphologically similar under H&E staining alone. BACKGROUND: In the PNET4 European randomised controlled trial, children with standard risk medulloblastoma were allocated to HFRT or to STRT. All received maintenance chemotherapy. Event-free survival was similar between the two treatment arms. HFRT was associated with worse growth and better questionnaire-based executive function 6.1 years post-diagnosis, especially in children aged 8 years at diagnosis. In children aged .10); WMI (5.20 [-2.07 to 12.47], p > .10), PSI (10.91 [-1.54 to 23.36], p = .08; FSIQ (5.28 [-4.23 to 14.79], p > .10). CONCLUSION: HFRT was associated with higher verbal IQ in children aged
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- 2014
33. Genome-Wide DNA Methylation Profiling as Frontline Diagnostics for Central Nervous System Embryonal Tumors in Hong Kong
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Tam, Otto C. H., primary, Ho, Ronnie S. L., additional, Chan, Shing, additional, Li, Kay K. W., additional, Lam, Tit-Leung, additional, Cheung, Elaine T. Y., additional, Cheung, Oi-Yee, additional, Ho, Wilson W. S., additional, Cheng, Kevin K. F., additional, Shing, Matthew M. K., additional, Ku, Dennis T. L., additional, Chung, Brian H. Y., additional, Yang, Wanling, additional, Chan, Godfrey C. F., additional, Ng, Ho-Keung, additional, and Liu, Anthony P. Y., additional
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- 2023
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34. Identifying predictors of glioma evolution from longitudinal sequencing
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Mu, Quanhua, primary, Chai, Ruichao, additional, Pang, Bo, additional, Yang, Yingxi, additional, Liu, Hanjie, additional, Zhao, Zheng, additional, Bao, Zhaoshi, additional, Song, Dong, additional, Zhu, Zhihan, additional, Yan, Mengli, additional, Jiang, Biaobin, additional, Mo, Zongchao, additional, Tang, Jihong, additional, Sa, Jason K., additional, Cho, Hee Jin, additional, Chang, Yuzhou, additional, Chan, Kaitlin Hao Yi, additional, Loi, Danson Shek Chun, additional, Tam, Sindy Sing Ting, additional, Chan, Aden Ka Yin, additional, Wu, Angela Ruohao, additional, Liu, Zhaoqi, additional, Poon, Wai Sang, additional, Ng, Ho Keung, additional, Chan, Danny Tat Ming, additional, Iavarone, Antonio, additional, Nam, Do-Hyun, additional, Jiang, Tao, additional, and Wang, Jiguang, additional
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- 2023
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35. ALTERNATIVE LENGTHENING OF TELOMERES (ALT) IS SEEN IN A PROPORTION OF OLIGODENDROGLIOMAS AND IT IS ASSOCIATED WITH A WORSE PROGNOSIS
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Ng, Ho Keung, primary, Li, Kay K K, additional, and Shi, Zhi-Feng, additional
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- 2023
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36. Recurrent noncoding U1 snRNA mutations drive cryptic splicing in SHH medulloblastoma
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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.
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- 2019
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37. Clinical and mutational profiles of adult medulloblastoma groups
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Wong, Gabriel Chun-Hei, Li, Kay Ka-Wai, Wang, Wei-Wei, Liu, Anthony Pak-Yin, Huang, Queenie Junqi, Chan, Aden Ka-Yin, Poon, Manix Fung-Man, Chung, Nellie Yuk-Fei, Wong, Queenie Hoi-Wing, Chen, Hong, Chan, Danny Tat Ming, Liu, Xian-Zhi, Mao, Ying, Zhang, Zhen-Yu, Shi, Zhi-Feng, and Ng, Ho-Keung
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- 2020
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38. The kinesin KIF14 is overexpressed in medulloblastoma and downregulation of KIF14 suppressed tumor proliferation and induced apoptosis
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Li, Kay Ka-Wai, Qi, Yan, Xia, Tian, Chan, Aden Ka-Yin, Zhang, Zhen-Yu, Aibaidula, Abudumijiti, Zhang, Rong, Zhou, Liangfu, Yao, Yu, and Ng, Ho-Keung
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- 2017
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39. Diagnostic Accuracy and Field for Improvement of Frameless Stereotactic Brain Biopsy: A Focus on Nondiagnostic Cases.
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He, Zhexi, Zhu, Cannon Xian Lun, Chan, Danny Tat Ming, Cheung, Tom Chi Yan, Ng, Ho-Keung, Mok, Vincent Chung Tong, and Poon, Wai Sang
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LITERATURE reviews ,BIOPSY ,COMPUTER-assisted surgery - Abstract
Background The diagnostic accuracy of frameless stereotactic brain biopsy has been reported, but there is limited literature focusing on the reasons for nondiagnostic cases. In this study, we evaluate the diagnostic accuracy of frameless stereotactic brain biopsy, compare it with the current international standard, and review the field for improvement. Methods This is a retrospective analysis of consecutive, prospectively collected frameless stereotactic brain biopsies from 2007 to 2020. We evaluated the diagnostic accuracy of the frameless stereotactic brain biopsies using defined criteria. The biopsy result was classified as conclusive, inconclusive, or negative, based on the pathologic, radiologic, and clinical diagnosis concordance. For inconclusive or negative results, we further evaluated the preoperative planning and postoperative imaging to review the errors. A literature review for the diagnostic accuracy of frameless stereotactic biopsy was performed for the validity of our results. Results There were 106 patients with 109 biopsies performed from 2007 to 2020. The conclusive diagnosis was reached in 103 (94.5%) procedures. An inconclusive diagnosis was noted in four (3.7%) procedures and the biopsy was negative in two (1.9%) procedures. Symptomatic hemorrhage occurred in one patient (0.9%). There was no mortality in our series. Registration error (RE) and inaccurate targeting occurred in three trigonal lesions (2.8%), sampling of the nonrepresentative part of the lesion occurred in two cases (1.8%), and one biopsy (0.9%) for lymphoma was negative due to steroid treatment. The literature review suggested that our diagnostic accuracy was comparable with the published literature. Conclusion The frameless stereotactic biopsy is a safe procedure with high diagnostic accuracy only if meticulous preoperative planning and careful intraoperative registration is performed. The common pitfalls precluding a conclusive diagnosis are RE and biopsies at nonrepresentative sites. [ABSTRACT FROM AUTHOR]
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- 2024
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40. Pediatric low-grade gliomas can be molecularly stratified for risk
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Yang, Rui Ryan, Aibaidula, Abudumijiti, Wang, Wei-wei, Chan, Aden Ka-Yin, Shi, Zhi-feng, Zhang, Zhen-yu, Chan, Danny Tat Ming, Poon, Wai Sang, Liu, Xian-zhi, Li, Wen-cai, Zhang, Rui-qi, Li, Yan-Xi, Chung, Nellie Yuk-Fei, Chen, Hong, Wu, Jingsong, Zhou, Liangfu, Li, Kay Ka-Wai, and Ng, Ho-Keung
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- 2018
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41. Oligodendrogliomas in pediatric and teenage patients only rarely exhibit molecular markers and patients have excellent survivals
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Li, Yan-Xi, Aibaidula, Abudumijiti, Shi, Zhifeng, Chen, Hong, Li, Kay Ka-Wai, Chung, Nellie Yuk-Fei, Yang, Ryan Rui, Chan, Danny Tat-Ming, Poon, Wai Sang, Lee, Ka Lok Ryan, Mao, Ying, Wu, Jinsong, Chan, Aden Ka-yin, Zhou, Liangfu, and Ng, Ho-Keung
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- 2018
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42. Functional diversity and cooperativity between subclonal populations of pediatric glioblastoma and diffuse intrinsic pontine glioma cells
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Vinci, Mara, Burford, Anna, Molinari, Valeria, Kessler, Ketty, Popov, Sergey, Clarke, Matthew, Taylor, Kathryn R., Pemberton, Helen N., Lord, Christopher J., Gutteridge, Alice, Forshew, Tim, Carvalho, Diana, Marshall, Lynley V., Qin, Elizabeth Y., Ingram, Wendy J., Moore, Andrew S., Ng, Ho-Keung, Trabelsi, Saoussen, H’mida-Ben Brahim, Dorra, Entz-Werle, Natacha, Zacharoulis, Stergios, Vaidya, Sucheta, Mandeville, Henry C., Bridges, Leslie R., Martin, Andrew J., Al-Sarraj, Safa, Chandler, Christopher, Sunol, Mariona, Mora, Jaume, de Torres, Carmen, Cruz, Ofelia, Carcaboso, Angel M., Monje, Michelle, Mackay, Alan, and Jones, Chris
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- 2018
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43. Data from Infant High-Grade Gliomas Comprise Multiple Subgroups Characterized by Novel Targetable Gene Fusions and Favorable Outcomes
- Author
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Clarke, Matthew, primary, Mackay, Alan, primary, Ismer, Britta, primary, Pickles, Jessica C., primary, Tatevossian, Ruth G., primary, Newman, Scott, primary, Bale, Tejus A., primary, Stoler, Iris, primary, Izquierdo, Elisa, primary, Temelso, Sara, primary, Carvalho, Diana M., primary, Molinari, Valeria, primary, Burford, Anna, primary, Howell, Louise, primary, Virasami, Alex, primary, Fairchild, Amy R., primary, Avery, Aimee, primary, Chalker, Jane, primary, Kristiansen, Mark, primary, Haupfear, Kelly, primary, Dalton, James D., primary, Orisme, Wilda, primary, Wen, Ji, primary, Hubank, Michael, primary, Kurian, Kathreena M., primary, Rowe, Catherine, primary, Maybury, Mellissa, primary, Crosier, Stephen, primary, Knipstein, Jeffrey, primary, Schüller, Ulrich, primary, Kordes, Uwe, primary, Kram, David E., primary, Snuderl, Matija, primary, Bridges, Leslie, primary, Martin, Andrew J., primary, Doey, Lawrence J., primary, Al-Sarraj, Safa, primary, Chandler, Christopher, primary, Zebian, Bassel, primary, Cairns, Claire, primary, Natrajan, Rachael, primary, Boult, Jessica K.R., primary, Robinson, Simon P., primary, Sill, Martin, primary, Dunkel, Ira J., primary, Gilheeney, Stephen W., primary, Rosenblum, Marc K., primary, Hughes, Debbie, primary, Proszek, Paula Z., primary, Macdonald, Tobey J., primary, Preusser, Matthias, primary, Haberler, Christine, primary, Slavc, Irene, primary, Packer, Roger, primary, Ng, Ho-Keung, primary, Caspi, Shani, primary, Popović, Mara, primary, Faganel Kotnik, Barbara, primary, Wood, Matthew D., primary, Baird, Lissa, primary, Davare, Monika Ashok, primary, Solomon, David A., primary, Olsen, Thale Kristin, primary, Brandal, Petter, primary, Farrell, Michael, primary, Cryan, Jane B., primary, Capra, Michael, primary, Karremann, Michael, primary, Schittenhelm, Jens, primary, Schuhmann, Martin U., primary, Ebinger, Martin, primary, Dinjens, Winand N.M., primary, Kerl, Kornelius, primary, Hettmer, Simone, primary, Pietsch, Torsten, primary, Andreiuolo, Felipe, primary, Driever, Pablo Hernáiz, primary, Korshunov, Andrey, primary, Hiddingh, Lotte, primary, Worst, Barbara C., primary, Sturm, Dominik, primary, Zuckermann, Marc, primary, Witt, Olaf, primary, Bloom, Tabitha, primary, Mitchell, Clare, primary, Miele, Evelina, primary, Colafati, Giovanna Stefania, primary, Diomedi-Camassei, Francesca, primary, Bailey, Simon, primary, Moore, Andrew S., primary, Hassall, Timothy E.G., primary, Lowis, Stephen P., primary, Tsoli, Maria, primary, Cowley, Mark J., primary, Ziegler, David S., primary, Karajannis, Matthias A., primary, Aquilina, Kristian, primary, Hargrave, Darren R., primary, Carceller, Fernando, primary, Marshall, Lynley V., primary, von Deimling, Andreas, primary, Kramm, Christof M., primary, Pfister, Stefan M., primary, Sahm, Felix, primary, Baker, Suzanne J., primary, Mastronuzzi, Angela, primary, Carai, Andrea, primary, Vinci, Maria, primary, Capper, David, primary, Popov, Sergey, primary, Ellison, David W., primary, Jacques, Thomas S., primary, Jones, David T.W., primary, and Jones, Chris, primary
- Published
- 2023
- Full Text
- View/download PDF
44. Supplementary Data from Infant High-Grade Gliomas Comprise Multiple Subgroups Characterized by Novel Targetable Gene Fusions and Favorable Outcomes
- Author
-
Clarke, Matthew, primary, Mackay, Alan, primary, Ismer, Britta, primary, Pickles, Jessica C., primary, Tatevossian, Ruth G., primary, Newman, Scott, primary, Bale, Tejus A., primary, Stoler, Iris, primary, Izquierdo, Elisa, primary, Temelso, Sara, primary, Carvalho, Diana M., primary, Molinari, Valeria, primary, Burford, Anna, primary, Howell, Louise, primary, Virasami, Alex, primary, Fairchild, Amy R., primary, Avery, Aimee, primary, Chalker, Jane, primary, Kristiansen, Mark, primary, Haupfear, Kelly, primary, Dalton, James D., primary, Orisme, Wilda, primary, Wen, Ji, primary, Hubank, Michael, primary, Kurian, Kathreena M., primary, Rowe, Catherine, primary, Maybury, Mellissa, primary, Crosier, Stephen, primary, Knipstein, Jeffrey, primary, Schüller, Ulrich, primary, Kordes, Uwe, primary, Kram, David E., primary, Snuderl, Matija, primary, Bridges, Leslie, primary, Martin, Andrew J., primary, Doey, Lawrence J., primary, Al-Sarraj, Safa, primary, Chandler, Christopher, primary, Zebian, Bassel, primary, Cairns, Claire, primary, Natrajan, Rachael, primary, Boult, Jessica K.R., primary, Robinson, Simon P., primary, Sill, Martin, primary, Dunkel, Ira J., primary, Gilheeney, Stephen W., primary, Rosenblum, Marc K., primary, Hughes, Debbie, primary, Proszek, Paula Z., primary, Macdonald, Tobey J., primary, Preusser, Matthias, primary, Haberler, Christine, primary, Slavc, Irene, primary, Packer, Roger, primary, Ng, Ho-Keung, primary, Caspi, Shani, primary, Popović, Mara, primary, Faganel Kotnik, Barbara, primary, Wood, Matthew D., primary, Baird, Lissa, primary, Davare, Monika Ashok, primary, Solomon, David A., primary, Olsen, Thale Kristin, primary, Brandal, Petter, primary, Farrell, Michael, primary, Cryan, Jane B., primary, Capra, Michael, primary, Karremann, Michael, primary, Schittenhelm, Jens, primary, Schuhmann, Martin U., primary, Ebinger, Martin, primary, Dinjens, Winand N.M., primary, Kerl, Kornelius, primary, Hettmer, Simone, primary, Pietsch, Torsten, primary, Andreiuolo, Felipe, primary, Driever, Pablo Hernáiz, primary, Korshunov, Andrey, primary, Hiddingh, Lotte, primary, Worst, Barbara C., primary, Sturm, Dominik, primary, Zuckermann, Marc, primary, Witt, Olaf, primary, Bloom, Tabitha, primary, Mitchell, Clare, primary, Miele, Evelina, primary, Colafati, Giovanna Stefania, primary, Diomedi-Camassei, Francesca, primary, Bailey, Simon, primary, Moore, Andrew S., primary, Hassall, Timothy E.G., primary, Lowis, Stephen P., primary, Tsoli, Maria, primary, Cowley, Mark J., primary, Ziegler, David S., primary, Karajannis, Matthias A., primary, Aquilina, Kristian, primary, Hargrave, Darren R., primary, Carceller, Fernando, primary, Marshall, Lynley V., primary, von Deimling, Andreas, primary, Kramm, Christof M., primary, Pfister, Stefan M., primary, Sahm, Felix, primary, Baker, Suzanne J., primary, Mastronuzzi, Angela, primary, Carai, Andrea, primary, Vinci, Maria, primary, Capper, David, primary, Popov, Sergey, primary, Ellison, David W., primary, Jacques, Thomas S., primary, Jones, David T.W., primary, and Jones, Chris, primary
- Published
- 2023
- Full Text
- View/download PDF
45. Supplementary Table S3 from Infant High-Grade Gliomas Comprise Multiple Subgroups Characterized by Novel Targetable Gene Fusions and Favorable Outcomes
- Author
-
Clarke, Matthew, primary, Mackay, Alan, primary, Ismer, Britta, primary, Pickles, Jessica C., primary, Tatevossian, Ruth G., primary, Newman, Scott, primary, Bale, Tejus A., primary, Stoler, Iris, primary, Izquierdo, Elisa, primary, Temelso, Sara, primary, Carvalho, Diana M., primary, Molinari, Valeria, primary, Burford, Anna, primary, Howell, Louise, primary, Virasami, Alex, primary, Fairchild, Amy R., primary, Avery, Aimee, primary, Chalker, Jane, primary, Kristiansen, Mark, primary, Haupfear, Kelly, primary, Dalton, James D., primary, Orisme, Wilda, primary, Wen, Ji, primary, Hubank, Michael, primary, Kurian, Kathreena M., primary, Rowe, Catherine, primary, Maybury, Mellissa, primary, Crosier, Stephen, primary, Knipstein, Jeffrey, primary, Schüller, Ulrich, primary, Kordes, Uwe, primary, Kram, David E., primary, Snuderl, Matija, primary, Bridges, Leslie, primary, Martin, Andrew J., primary, Doey, Lawrence J., primary, Al-Sarraj, Safa, primary, Chandler, Christopher, primary, Zebian, Bassel, primary, Cairns, Claire, primary, Natrajan, Rachael, primary, Boult, Jessica K.R., primary, Robinson, Simon P., primary, Sill, Martin, primary, Dunkel, Ira J., primary, Gilheeney, Stephen W., primary, Rosenblum, Marc K., primary, Hughes, Debbie, primary, Proszek, Paula Z., primary, Macdonald, Tobey J., primary, Preusser, Matthias, primary, Haberler, Christine, primary, Slavc, Irene, primary, Packer, Roger, primary, Ng, Ho-Keung, primary, Caspi, Shani, primary, Popović, Mara, primary, Faganel Kotnik, Barbara, primary, Wood, Matthew D., primary, Baird, Lissa, primary, Davare, Monika Ashok, primary, Solomon, David A., primary, Olsen, Thale Kristin, primary, Brandal, Petter, primary, Farrell, Michael, primary, Cryan, Jane B., primary, Capra, Michael, primary, Karremann, Michael, primary, Schittenhelm, Jens, primary, Schuhmann, Martin U., primary, Ebinger, Martin, primary, Dinjens, Winand N.M., primary, Kerl, Kornelius, primary, Hettmer, Simone, primary, Pietsch, Torsten, primary, Andreiuolo, Felipe, primary, Driever, Pablo Hernáiz, primary, Korshunov, Andrey, primary, Hiddingh, Lotte, primary, Worst, Barbara C., primary, Sturm, Dominik, primary, Zuckermann, Marc, primary, Witt, Olaf, primary, Bloom, Tabitha, primary, Mitchell, Clare, primary, Miele, Evelina, primary, Colafati, Giovanna Stefania, primary, Diomedi-Camassei, Francesca, primary, Bailey, Simon, primary, Moore, Andrew S., primary, Hassall, Timothy E.G., primary, Lowis, Stephen P., primary, Tsoli, Maria, primary, Cowley, Mark J., primary, Ziegler, David S., primary, Karajannis, Matthias A., primary, Aquilina, Kristian, primary, Hargrave, Darren R., primary, Carceller, Fernando, primary, Marshall, Lynley V., primary, von Deimling, Andreas, primary, Kramm, Christof M., primary, Pfister, Stefan M., primary, Sahm, Felix, primary, Baker, Suzanne J., primary, Mastronuzzi, Angela, primary, Carai, Andrea, primary, Vinci, Maria, primary, Capper, David, primary, Popov, Sergey, primary, Ellison, David W., primary, Jacques, Thomas S., primary, Jones, David T.W., primary, and Jones, Chris, primary
- Published
- 2023
- Full Text
- View/download PDF
46. Data from Sirtuin 1 Is Upregulated in a Subset of Hepatocellular Carcinomas where It Is Essential for Telomere Maintenance and Tumor Cell Growth
- Author
-
Chen, Juan, primary, Zhang, Bin, primary, Wong, Nathalie, primary, Lo, Anthony W.I., primary, To, Ka-Fai, primary, Chan, Anthony W.H., primary, Ng, Margaret H.L., primary, Ho, Cecilia Y.S., primary, Cheng, Suk-Hang, primary, Lai, Paul B.S., primary, Yu, Jun, primary, Ng, Ho-Keung, primary, Ling, Ming-Tat, primary, Huang, Ai-Long, primary, Cai, Xue-Fei, primary, and Ko, Ben C.B., primary
- Published
- 2023
- Full Text
- View/download PDF
47. Supplementary Information from Sirtuin 1 Is Upregulated in a Subset of Hepatocellular Carcinomas where It Is Essential for Telomere Maintenance and Tumor Cell Growth
- Author
-
Chen, Juan, primary, Zhang, Bin, primary, Wong, Nathalie, primary, Lo, Anthony W.I., primary, To, Ka-Fai, primary, Chan, Anthony W.H., primary, Ng, Margaret H.L., primary, Ho, Cecilia Y.S., primary, Cheng, Suk-Hang, primary, Lai, Paul B.S., primary, Yu, Jun, primary, Ng, Ho-Keung, primary, Ling, Ming-Tat, primary, Huang, Ai-Long, primary, Cai, Xue-Fei, primary, and Ko, Ben C.B., primary
- Published
- 2023
- Full Text
- View/download PDF
48. Supplementary Figure 2 from Sirtuin 1 Is Upregulated in a Subset of Hepatocellular Carcinomas where It Is Essential for Telomere Maintenance and Tumor Cell Growth
- Author
-
Chen, Juan, primary, Zhang, Bin, primary, Wong, Nathalie, primary, Lo, Anthony W.I., primary, To, Ka-Fai, primary, Chan, Anthony W.H., primary, Ng, Margaret H.L., primary, Ho, Cecilia Y.S., primary, Cheng, Suk-Hang, primary, Lai, Paul B.S., primary, Yu, Jun, primary, Ng, Ho-Keung, primary, Ling, Ming-Tat, primary, Huang, Ai-Long, primary, Cai, Xue-Fei, primary, and Ko, Ben C.B., primary
- Published
- 2023
- Full Text
- View/download PDF
49. Supplementary Figure 5 from Sirtuin 1 Is Upregulated in a Subset of Hepatocellular Carcinomas where It Is Essential for Telomere Maintenance and Tumor Cell Growth
- Author
-
Chen, Juan, primary, Zhang, Bin, primary, Wong, Nathalie, primary, Lo, Anthony W.I., primary, To, Ka-Fai, primary, Chan, Anthony W.H., primary, Ng, Margaret H.L., primary, Ho, Cecilia Y.S., primary, Cheng, Suk-Hang, primary, Lai, Paul B.S., primary, Yu, Jun, primary, Ng, Ho-Keung, primary, Ling, Ming-Tat, primary, Huang, Ai-Long, primary, Cai, Xue-Fei, primary, and Ko, Ben C.B., primary
- Published
- 2023
- Full Text
- View/download PDF
50. Supplementary Figure 4 from Sirtuin 1 Is Upregulated in a Subset of Hepatocellular Carcinomas where It Is Essential for Telomere Maintenance and Tumor Cell Growth
- Author
-
Chen, Juan, primary, Zhang, Bin, primary, Wong, Nathalie, primary, Lo, Anthony W.I., primary, To, Ka-Fai, primary, Chan, Anthony W.H., primary, Ng, Margaret H.L., primary, Ho, Cecilia Y.S., primary, Cheng, Suk-Hang, primary, Lai, Paul B.S., primary, Yu, Jun, primary, Ng, Ho-Keung, primary, Ling, Ming-Tat, primary, Huang, Ai-Long, primary, Cai, Xue-Fei, primary, and Ko, Ben C.B., primary
- Published
- 2023
- Full Text
- View/download PDF
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