Medulloblastomics revisited: biological and clinical insights from thousands of patients
Open accessAbstract
Medulloblastoma, a malignant brain tumour primarily diagnosed during childhood, has recently been the focus of intensive molecular profiling efforts, profoundly advancing our understanding of biologically and clinically heterogeneous disease subgroups. Genomic, epigenomic, transcriptomic and proteomic landscapes have now been mapped for an unprecedented number of bulk samples from patients with medulloblastoma and, more recently, for single medulloblastoma cells. These efforts have provided pivotal new insights into the diverse molecular mechanisms presumed to drive tumour initiation, maintenance and recurrence across individual subgroups and subtypes. Translational opportunities stemming from this knowledge are continuing to evolve, providing a framework for improved diagnostic and therapeutic interventions. In this Review, we summarize recent advances derived from this continued molecular characterization of medulloblastoma and contextualize this progress towards the deployment of more effective, molecularly informed treatments for affected patients.
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An autocrine ActivinB mechanism drives TGFβ/Activin signaling in Group 3 medulloblastoma
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Self-citationZomerman, W. W., Plasschaert, S. L. A., Conroy, S., Scherpen, F. J. G., Boer, T. M.-D., Lourens, H.-J., Llobet, S. G., Smit, M. J., Slagter‐Menkema, L., Seitz, A., et al. (2018) · Neuro-Oncology · doi:10.1093/neuonc/noy059.481 · Cited by 9 · see citing works
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- [122]Sharma T Second-generation molecular subgrouping of medulloblastoma: an international meta-analysis of Group 3 and Group 4 subtypes. Acta Neuropathol 138, 309– 326, doi: 10.1007/s00401-019-02020-0 (2019). 31076851 PMC6660496 · DOI · Paper page
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The 2021 WHO classification of tumors of the central nervous system: a summary
Louis, D. N., Perry, A., Wesseling, P., Brat, D. J., Cree, I. A., Figarella-Branger, D., Hawkins, C., Ng, H. K., Pfister, S. M., Reifenberger, G., et al. (2021) · Neuro-Oncology · doi:10.1093/neuonc/noab106 · Cited by 12,273 · see citing works
Self-citationNavigating the DNA methylation landscape of cancer
Nishiyama, A., & Nakanishi, M. (2021) · Trends in Genetics · doi:10.1016/j.tig.2021.05.002 · Cited by 974 · see citing works
Horbinski, C., Berger, T., Packer, R. J., & Wen, P. Y. (2022) · Nature Reviews Neurology · doi:10.1038/s41582-022-00679-w · Cited by 312 · see citing works
Gajjar, A., Robinson, G. W., Smith, K. S., Lin, T., Merchant, T. E., Chintagumpala, M., Mahajan, A., Su, J., Bouffet, E., Bartels, U., et al. (2021) · Journal of Clinical Oncology · doi:10.1200/jco.20.01372 · Cited by 241 · see citing works
Self-citationThe 2021 WHO Classification of Tumors of the Central Nervous System: clinical implications
Wen, P. Y., & Packer, R. J. (2021) · Neuro-Oncology · doi:10.1093/neuonc/noab120 · Cited by 241 · see citing works
A roadmap for the Human Developmental Cell Atlas
Haniffa, M. A., Taylor, D. M., Linnarsson, S., Aronow, B. J., Bader, G. D., Barker, R. A., Cámara, P. G., Camp, J. G., Chédotal, A., Copp, A. J., et al. (2021) · Nature · doi:10.1038/s41586-021-03620-1 · Cited by 184 · see citing works
Baxi, E. G., Thompson, T. G., Li, J., Kaye, J., Lim, R. G., Wu, J., Ramamoorthy, D., Lima, L. D. A., Vaibhav, V., Matlock, A. D., et al. (2022) · Nature Neuroscience · doi:10.1038/s41593-021-01006-0 · Cited by 159 · see citing works
Unified rhombic lip origins of group 3 and group 4 medulloblastoma
Smith, K. S., Bihannic, L., Gudenas, B. L., Haldipur, P., Tao, R., Gao, Q., Li, Y., Aldinger, K. A., Iskusnykh, I. Y., Chizhikov, V. V., et al. (2022) · Nature · doi:10.1038/s41586-022-05208-9 · Cited by 161 · see citing works
Self-citationEscudero, L., Llort, A., Arias, A., Díaz‐Navarro, A., Ricarte, F. M., Rubio-Pérez, C., Mayor, R., Caratù, G., Martínez-Sáez, E. A., Méndez, E. V., et al. (2020) · Nature Communications · doi:10.1038/s41467-020-19175-0 · Cited by 124 · see citing works
“…TP53 CTNNB1 PTCH1 BCOR KMT2D Mutations CNVs Identification of MB molecular features Cytogenetics Mutations CNVs WES 13 MB MB classification system Hovestadt et al., 2020 WNT SHH (α, β, γ, δ) Group3 /Group4 (I-VIII) WNT SHH-Child, SHH-Infant Group3-LR, Group3-HR, Group4-LR, Group4-HR Schwalbe et…”
Mass spectrometry‐based tear proteomics for noninvasive biomarker discovery
Ponzini, E., Santambrogio, C., Palma, A. D., Mauri, P., Tavazzi, S., & Grandori, R. (2021) · Mass Spectrometry Reviews · doi:10.1002/mas.21691 · Cited by 93 · see citing works
Iorgulescu, J. B., Sun, C., Neff, C., Cioffi, G., Gutierrez, C., Kruchko, C. A., Ruhl, J., Waite, K. A., Negoita, S., Hofferkamp, J., et al. (2022) · Neuro-Oncology · doi:10.1093/neuonc/noac113 · Cited by 75 · see citing works
Paskeh, M. D. A., Mehrabi, A., Gholami, M. H., Zabolian, A., Ranjbar, E., Saleki, H., Ranjbar, A., Hashemi, M., Ertaş, Y. N., Hushmandi, K., et al. (2021) · Biomedicine & Pharmacotherapy · doi:10.1016/j.biopha.2021.112532 · Cited by 74 · see citing works
La classification de l’OMS 2021 des tumeurs du système nerveux central
Figarella-Branger, D. F., Appay, R., Métais, A., Tauziède‐Espariat, A., Colin, C., Rousseau, A., & Varlet, P. (2021) · Annales de Pathologie · doi:10.1016/j.annpat.2021.11.005 · Cited by 74 · see citing works
Human Cerebellar Development and Transcriptomics: Implications for Neurodevelopmental Disorders
Haldipur, P., Millen, K. J., & Aldinger, K. A. (2022) · Annual Review of Neuroscience · doi:10.1146/annurev-neuro-111020-091953 · Cited by 74 · see citing works
The SHH/GLI signaling pathway: a therapeutic target for medulloblastoma
Lospinoso Severini, L., Ghirga, F., Bufalieri, F., Quaglio, D., Infante, P., & Di Marcotullio, L. (2020) · Expert Opinion on Therapeutic Targets · doi:10.1080/14728222.2020.1823967 · Cited by 61 · see citing works
ctDNA-Based Liquid Biopsy of Cerebrospinal Fluid in Brain Cancer
Escudero, L., Ricarte, F. M., & Seoane, J. (2021) · Cancers · doi:10.3390/cancers13091989 · Cited by 61 · see citing works
Methylation classifiers: Brain tumors, sarcomas, and what's next
Koelsche, C., & von Deimling, A. (2022) · Genes Chromosomes and Cancer · doi:10.1002/gcc.23041 · Cited by 62 · see citing works
“to non-WNT/non-SHH), are clinically more homogenous than the previously diagnosed classical, desmoplastic, extensively nodular, large cell, or anaplastic medulloblastomas.(67) Currently, further subgrouping”
BackgroundLazow, M., Palmer, J. D., Fouladi, M., & Salloum, R. (2022) · Neurotherapeutics · doi:10.1007/s13311-022-01273-0 · Cited by 58 · see citing works
“1 3 Finally, despite an improved understanding of biologically distinct subtypes within group 3 (as well as group 4) medulloblastoma defined by methylomic and transcriptomic profiles [43, 45], translation of findings into subtype-specific clinical treatment has lagged; future efforts should therefore seek to identify…”
BackgroundMedulloblastoma: Molecular understanding, treatment evolution, and new developments
Liu, X., Ding, C., Tan, W., & Zhang, A. (2020) · Pharmacology & Therapeutics · doi:10.1016/j.pharmthera.2020.107516 · Cited by 54 · see citing works
Clinical and mutational profiles of adult medulloblastoma groups
Wong, G. C.-H., Li, K. K., Wang, W., Liu, A. P. Y., Huang, Q. J., Chan, A. K., Poon, M. F., Chung, N. Y., Wong, Q. H., Chen, H., et al. (2020) · Acta Neuropathologica Communications · doi:10.1186/s40478-020-01066-6 · Cited by 54 · see citing works
Неганова, М. Е., Aleksandrova, Y. R., Sukocheva, O. A., & Klochkov, S. G. (2022) · Seminars in Cancer Biology · doi:10.1016/j.semcancer.2022.06.011 · Cited by 56 · see citing works
Endersby, R., Whitehouse, J. P., Pribnow, A. K., Kuchibhotla, M., Hii, H. L., Carline, B., Gande, S., Stripay, J. L., Ancliffe, M., Howlett, M., et al. (2021) · Science Translational Medicine · doi:10.1126/scitranslmed.aba7401 · Cited by 47 · see citing works
“G3-II and SHH are especially aggressive disease subtypes and the most likely to be refractory to current therapy (4).”
BackgroundInfluentialSelf-citationAttallah, O. (2021) · Frontiers in Neuroinformatics · doi:10.3389/fninf.2021.663592 · Cited by 47 · see citing works
“It evolves within the cerebellum on the posterior area of the brain and progresses rapidly to other parts of the brain (Hovestadt et al., 2020).”
BackgroundReichl, B., Niederstaetter, L., Bögl, T., Neuditschko, B., Bileck, A., Gojo, J., Buchberger, W. W., Peyrl, A., & Gerner, C. (2020) · Cancers · doi:10.3390/cancers12061350 · Cited by 46 · see citing works
The role of chromatin remodeler SMARCA4/BRG1 in brain cancers: a potential therapeutic target
Navickas, S. M., Giles, K. A., Brettingham‐Moore, K. H., & Taberlay, P. C. (2023) · Oncogene · doi:10.1038/s41388-023-02773-9 · Cited by 45 · see citing works
“More recent studies have discovered that these principal groups can be further stratified within groups, with an important distinction made for SHH group tumours based on TP53 status as TP53-mutant patients exhibit significantly poorer prognosis compared to TP53-wild-type patients [45, 46].”
BackgroundTargeting MYCN in Molecularly Defined Malignant Brain Tumors
Borgenvik, A., Čančer, M., Hutter, S., & Swartling, F. J. (2021) · Frontiers in Oncology · doi:10.3389/fonc.2020.626751 · Cited by 42 · see citing works
“Integrative genomic studies have shown that MB is not a single entity, but rather a heterogeneous group with distinct clinical and biologic features (6).”
BackgroundInfluentialSelf-citationNazio, F., Pò, A., Abballe, L., Ballabio, C., Diomedi‐Camassei, F., Bordi, M., Camera, A., Caruso, S., Caruana, I., Pezzullo, M., et al. (2021) · Acta Neuropathologica · doi:10.1007/s00401-021-02347-7 · Cited by 40 · see citing works
“More recently, using multiple complementary bioinformatic approaches, a study refined Group 3/4 classification, identifying eight subtypes (I–VIII), and describing a more complex intratumoral heterogeneity within Group 3 and 4 [39, 84].”
MethodAttallah, O., & Zaghlool, S. B. (2022) · Life · doi:10.3390/life12020232 · Cited by 38 · see citing works
“MB is a small blue cell malignancy of the cerebellum, which eventually progresses to other brain regions [3].”
BackgroundMolecular determinants of medulloblastoma metastasis and leptomeningeal dissemination
Li, M., Deng, Y., & Zhang, W. (2021) · Molecular Cancer Research · doi:10.1158/1541-7786.mcr-20-1026 · Cited by 37 · see citing works
“The classification of medulloblastoma has evolved from only relying on histopathological features to its combination with molecular characteristics (2).”
BackgroundAdolescents and Young Adults With Cancer: CNS Tumors
Wu, J., Heidelberg, R. E., & Gajjar, A. J. (2023) · Journal of Clinical Oncology · doi:10.1200/jco.23.01747 · Cited by 35 · see citing works
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Castro, L. N. G., Liu, I., & Filbin, M. G. (2022) · Neuro-Oncology · doi:10.1093/neuonc/noac211 · Cited by 34 · see citing works
Clinical Utility of Precision Medicine in Pediatric Oncology: A Systematic Review
Lee, J., Gillam, L. H., Visvanathan, K., Hansford, J. R., & McCarthy, M. (2021) · JCO Precision Oncology · doi:10.1200/po.20.00405 · Cited by 32 · see citing works
Posterior fossa tumors in children: current insights
Formentin, C., Joaquim, A. F., & Ghizoni, E. (2023) · European Journal of Pediatrics · doi:10.1007/s00431-023-05189-5 · Cited by 33 · see citing works
Molecular Testing for the World Health Organization Classification of Central Nervous System Tumors
Horbinski, C., Solomon, D. A., Lukas, R. V., Packer, R. J., Brastianos, P. K., Wen, P. Y., Snuderl, M., Berger, M. S., Chang, S. M., Fouladi, M., et al. (2024) · JAMA Oncology · doi:10.1001/jamaoncol.2024.5506 · Cited by 31 · see citing works
Bagchi, A., Dhanda, S. K., Dunphy, P., Sioson, E., & Robinson, G. W. (2023) · Journal of the National Comprehensive Cancer Network · doi:10.6004/jnccn.2023.7024 · Cited by 28 · see citing works
“This distribution is in contrast to older children, in which the WNT molecular group forms 10% and G4 becomes the dominant group ( 45%).(2) This phenomenon has consequences for clinical trials because a cohort of infants will reflect the SHH group response, whereas inclusion of young children unwittingly adds a signif…”
ResultSelf-citationWang, Y.-R., Wang, P., Yan, Z., Zhou, Q., Güntürkün, F., Li, P., Hu, Y., Wu, W. E., Zhao, K., Zhang, M., et al. (2024) · Cancer Cell · doi:10.1016/j.ccell.2024.06.002 · Cited by 31 · see citing works
Andradas, C., Byrne, J., Kuchibhotla, M., Ancliffe, M., Jones, A. C., Carline, B., Hii, H. L., Truong, A., Storer, L. C. D., Ritzmann, T. A., et al. (2021) · Cancers · doi:10.3390/cancers13020330 · Cited by 28 · see citing works
“Extensive m lecular characeriz tion of both cancers [3,11] has not led to successful tran lation of many novel therapies to the clinic, even with focused efforts to develop drugs that target specific mutations in these diseases.”
BackgroundDormant SOX9-Positive Cells Facilitate MYC-Driven Recurrence of Medulloblastoma
Borgenvik, A., Holmberg, K. O., Bolin, S., Zhao, M., Savov, V., Rosén, G., Hutter, S., Garancher, A., Rahmanto, A. S., Bergström, T., et al. (2022) · Cancer Research · doi:10.1158/0008-5472.can-22-2108 · Cited by 28 · see citing works
Self-citationRelapsed Medulloblastoma in Pre-Irradiated Patients: Current Practice for Diagnostics and Treatment
Hill, R. M., Plasschaert, S. L. A., Timmermann, B., Dufour, C., Aquilina, K., Avula, S., Donovan, L., Lequin, M. H., Pietsch, T., Thomale, U. W., et al. (2021) · Cancers · doi:10.3390/cancers14010126 · Cited by 27 · see citing works
Self-citationComplement C3a activates astrocytes to promote medulloblastoma progression through TNF-α
Gong, B., Guo, D., Zheng, C., Ma, Z., Zhang, J., Qu, Y., Li, X., Li, G. L., Zhang, L., & Wang, Y. (2022) · Journal of Neuroinflammation · doi:10.1186/s12974-022-02516-9 · Cited by 26 · see citing works
“Current hot spots of MB research focus on investigating the molecular profiles and mechanisms of tumor cells themselves [8].”
Morris, E. K., Daignault, S. M., Stehbens, S. J., Genovesi, L. A., & Lagendijk, A. K. (2023) · Frontiers in Oncology · doi:10.3389/fonc.2023.1101522 · Cited by 27 · see citing works
Focusing on brain tumours and brain metastasis
(2019) · Nature reviews. Cancer · doi:10.1038/s41568-019-0232-7 · Cited by 26 · see citing works
Schönholzer, M. T., Migliavacca, J., Alvarez, E., Kumar, K. S., Neve, A., Gries, A., Ma, M., Grotzer, M. A., & Baumgartner, M. (2020) · Neoplasia · doi:10.1016/j.neo.2020.07.006 · Cited by 22 · see citing works
“With CD271 [2] and BMI1 [10] two such biomarkers were identified for sonic hedgehog (SHH) and Group 4 (Gr4) MB tumors [9], respectively.”
BackgroundSlika, H., Alimonti, P., Raj, D., Caraway, C. A., Alomari, S., Jackson, E. M., & Tyler, B. (2023) · Cancers · doi:10.3390/cancers15153889 · Cited by 23 · see citing works
Godbole, S., Voß, H., Gocke, A., Schlumbohm, S., Schumann, Y., Peng, B., Mynarek, M., Rutkowski, S., Dottermusch, M., Dorostkar, M. M., et al. (2024) · Nature Communications · doi:10.1038/s41467-024-50554-z · Cited by 26 · see citing works
Self-citationGroup 3 medulloblastoma transcriptional networks collapse under domain specific EP300/CBP inhibition
Shendy, N. A. M., Bikowitz, M. J., Sigua, L. H., Zhang, Y., Mercier, A. L., Khashana, Y., Nance, S., Liu, Q., Delahunty, I. M., Robinson, S., et al. (2024) · Nature Communications · doi:10.1038/s41467-024-47102-0 · Cited by 21 · see citing works
“Medulloblastoma (MB) is an aggressive pediatric malignant brain tumor composed of distinct disease subtypes regulated by different driver oncogenes 38 – 41 .”
Statins repress hedgehog signaling in medulloblastoma with no bone toxicities
Fan, Q., Gong, T., Zheng, C., Ng, J. M. Y., Chen, J., Myers, C. B., Hensley, H. H., Curran, T., & Yang, Z.-J. (2021) · Oncogene · doi:10.1038/s41388-021-01701-z · Cited by 21 · see citing works
Immune cell landscape and immunotherapy of medulloblastoma
Zhang, J., & Wang, T. (2021) · Pediatric Investigation · doi:10.1002/ped4.12261 · Cited by 21 · see citing works
Mynarek, M., Obrecht, D., Sill, M., Sturm, D., Kloth‐Stachnau, K., Selt, F., Ecker, J., von Hoff, K., Juhnke, B.-O., Goschzik, T., et al. (2022) · Acta Neuropathologica · doi:10.1007/s00401-022-02522-4 · Cited by 24 · see citing works
Self-citationSuppressing recurrence in Sonic Hedgehog subgroup medulloblastoma using the OLIG2 inhibitor CT-179
Li, Y., Lim, C., Dismuke, T., Malawsky, D. S., Oasa, S., Bruce, Z. C., Offenhäuser, C., Baumgartner, U., D’Souza, R. C. J., Edwards, S. L., et al. (2025) · Nature Communications · doi:10.1038/s41467-024-54861-3 · Cited by 23 · see citing works
Medulloblastoma Drugs in Development: Current Leads, Trials and Drawbacks
Wen, J.-C., & Hadden, M. K. (2021) · European journal of medicinal chemistry · doi:10.1016/j.ejmech.2021.113268 · Cited by 18 · see citing works
Cooperation of Striatin 3 and MAP4K4 promotes growth and tissue invasion
Migliavacca, J., Züllig, B., Capdeville, C., Grotzer, M. A., & Baumgartner, M. (2022) · Communications Biology · doi:10.1038/s42003-022-03708-y · Cited by 19 · see citing works
Pediatric brain tumor cell lines exhibit miRNA-depleted, Y RNA-enriched extracellular vesicles
Magaña, S. M., Peterson, T. E., Evans, J. M., Decker, P. A., Simon, V. A., Eckel‐Passow, J. E., Daniels, D. J., & Parney, I. F. (2022) · Journal of Neuro-Oncology · doi:10.1007/s11060-021-03914-4 · Cited by 19 · see citing works
“Despite multimodal treatment algorithms including surgical resection and radiochemotherapy, 20–40% of MB patients succumb to their disease; those who survive suffer severe long-term, treatment-related side effects [3, 4].”
BackgroundInfluentialMainwaring, O. J., Weishaupt, H., Zhao, M., Rosén, G., Borgenvik, A., Breinschmid, L., Verbaan, A. D., Richardson, S., Thompson, D., Clifford, S. C., et al. (2023) · Nature Communications · doi:10.1038/s41467-023-36847-9 · Cited by 19 · see citing works
Self-citationTargeted treatment of solid tumors in pediatric precision oncology
Bertacca, I., Pegoraro, F., Tondo, A., & Favre, C. (2023) · Frontiers in Oncology · doi:10.3389/fonc.2023.1176790 · Cited by 18 · see citing works
Ghasemi, D. R., Okonechnikov, K., Rademacher, A., Tirier, S. M., Maaß, K. K., Schumacher, H., Joshi, P. K., Gold, M. P., Sundheimer, J. K., Statz, B., et al. (2024) · Nature Communications · doi:10.1038/s41467-023-44117-x · Cited by 18 · see citing works
“5a, Supplementary Data 6).”
InfluentialSelf-citationDrug Delivery Systems for Hedgehog Inhibitors in the Treatment of SHH-Medulloblastoma
Caimano, M., Severini, L. L., Loricchio, E., Infante, P., & Marcotullio, L. D. (2021) · Frontiers in Chemistry · doi:10.3389/fchem.2021.688108 · Cited by 18 · see citing works
“The latest classification recognizes four MB subgroups—wingless (WNT), sonic-hedgehog (SHH), group 3 (G3), and group 4 (G4)—each with different origins, genetic profiles, and variable prognoses, making the identification of a successful therapeutic strategy very difficult (Northcott et al., 2019; Hovestadt et al., 202…”
BackgroundVeliparib Is an Effective Radiosensitizing Agent in a Preclinical Model of Medulloblastoma
Buck, J. M., Dyer, P., Hii, H. L., Carline, B., Kuchibhotla, M., Byrne, J., Howlett, M., Whitehouse, J. P., Ebert, M. A., McDonald, K. L., et al. (2021) · Frontiers in Molecular Biosciences · doi:10.3389/fmolb.2021.633344 · Cited by 17 · see citing works
The Non-coding Side of Medulloblastoma
Laneve, P., & Caffarelli, E. (2020) · Frontiers in Cell and Developmental Biology · doi:10.3389/fcell.2020.00275 · Cited by 16 · see citing works
“Anatomically, these tumors have a midline vermian location adjacent to the fourth ventricle (Taylor et al., 2012; Perreault et al., 2014; Hovestadt et al., 2020).”
BackgroundInfluentialAdvances on Epigenetic Drugs for Pediatric Brain Tumors
Skouras, P., Markouli, M., Strepkos, D., & Piperi, C. (2022) · Current Neuropharmacology · doi:10.2174/1570159x20666220922150456 · Cited by 16 · see citing works
Marabitti, V., Giansanti, M., Mitri, F. D., Gatto, F., Mastronuzzi, A., & Nazio, F. (2022) · Frontiers in Cell and Developmental Biology · doi:10.3389/fcell.2022.1007641 · Cited by 16 · see citing works
“approximately one-third of MB diagnoses, it is of paramount importance to expand our knowledge about the other MB subgroups that likely arise from different tumor-initiating populations (Hovestadt et al., 2020).”
BackgroundN-myc–Mediated Translation Control Is a Therapeutic Vulnerability in Medulloblastoma
Kuzuoğlu‐Öztürk, D., Aksoy, O., Schmidt, C., Lea, R., Larson, J. D., Phelps, R. R. L., Nasholm, N. M., Holt, M., Contreras, A., Huang, M., et al. (2022) · Cancer Research · doi:10.1158/0008-5472.can-22-0945 · Cited by 13 · see citing works
Review of the Recent Changes in the WHO Classification for Pediatric Brain and Spinal Cord Tumors
Halfpenny, A. M., & Wood, M. D. (2023) · Pediatric Neurosurgery · doi:10.1159/000528957 · Cited by 16 · see citing works
“Genetic and epigenetic analysis supports that there are many more molecularly distinct medulloblastoma subtypes, including about 8 subclasses within the non-WNT/non-SHH (group 3/4) tumors [63].”
BackgroundLuo, Y., Zhuang, Y., Zhang, S., Wang, J., Teng, S., & Zeng, H. (2023) · Academic Radiology · doi:10.1016/j.acra.2023.06.023 · Cited by 16 · see citing works
Surviving the hunger games: Metabolic reprogramming in medulloblastoma
Manfreda, L., Rampazzo, E., Persano, L., Viola, G., & Bortolozzi, R. (2023) · Biochemical Pharmacology · doi:10.1016/j.bcp.2023.115697 · Cited by 15 · see citing works
Rahmani, E. S., Lawarde, A., Lingasamy, P., Moreno, S. V., Salumets, A., & Modhukur, V. (2023) · Frontiers in Genetics · doi:10.3389/fgene.2023.1233657 · Cited by 15 · see citing works
“To overcome this issue, integration of multi-omics data (including DNA methylation, gene expression, and clinical features) and application of machine learning algorithms for the development of accurate classification models are required (Hovestadt et al., 2020).”
Targeting DNA Methylation Machinery in Pediatric Solid Tumors
Cristalli, C., & Scotlandi, K. (2024) · Cells · doi:10.3390/cells13141209 · Cited by 14 · see citing works
“Over the years, MB has been extensively sequenced by distinct -omics (that is, genomic, epigenomic, transcriptomic, and proteomic) [105] and, as a result, the molecular classification of MB has evolved beyond the four consensus subgroups to include additional subdivisions (also referred to as…”
BackgroundLuo, Z., Dong, X., Yu, J., Xia, Y., Berry, K., Rao, R., Xu, L., Xue, P., Chen, T., Lin, Y., et al. (2021) · Frontiers in Cell and Developmental Biology · doi:10.3389/fcell.2021.634056 · Cited by 14 · see citing works
PRDM6 promotes medulloblastoma by repressing chromatin accessibility and altering gene expression
Schmidt, C., Cohen, S., Gudenas, B. L., Husain, S., Carlson, A., Westelman, S., Wang, L., Phillips, J. J., Northcott, P. A., Weiss, W. A., et al. (2024) · Scientific Reports · doi:10.1038/s41598-024-66811-6 · Cited by 14 · see citing works
Self-citationModeling craniopharyngioma for drug screening reveals a neuronal mechanism for tumor growth
Li, S., Li, W., Miao, Y., Gao, M., Jia, Y., Chen, Z., Chen, X., Pan, T., Zhang, S., Xing, Z., et al. (2024) · Science Translational Medicine · doi:10.1126/scitranslmed.adn6763 · Cited by 14 · see citing works
Capdeville, C., Russo, L. A., Pentón, D., Migliavacca, J., Zecevic, M., Gries, A., Neuhauss, S. C. F., Grotzer, M. A., & Baumgartner, M. (2022) · Life Science Alliance · doi:10.26508/lsa.202201380 · Cited by 13 · see citing works
“niospinal irradiation followed by chemotherapy (11).”
SALL4 is a CRL3REN/KCTD11 substrate that drives Sonic Hedgehog-dependent medulloblastoma
Lospinoso Severini, L., Loricchio, E., Navacci, S., Basili, I., Alfonsi, R., Bernardi, F., Moretti, M., Conenna, M., Cucinotta, A., Coni, S., et al. (2024) · Cell Death & Differentiation · doi:10.1038/s41418-023-01246-6 · Cited by 13 · see citing works
“In the last decade, whole genome sequencing approaches have de fi ned speci fi c mutational spectra and epigenetic pro fi ling leading to the identi fi cation of distinct subgroups, namely Wingless (WNT), Sonic Hedgehog (SHH), and non-WNT/non-SHH, comprising Group 3 (G3) and Group 4 (G4) [2].”
Self-citationBou‐Rouphael, J., & Durand, B. (2021) · Frontiers in Cell and Developmental Biology · doi:10.3389/fcell.2021.784998 · Cited by 13 · see citing works
Drivers Underlying Metastasis and Relapse in Medulloblastoma and Targeting Strategies
Holmberg, K. O., Borgenvik, A., Zhao, M., Giraud, G., & Swartling, F. J. (2024) · Cancers · doi:10.3390/cancers16091752 · Cited by 13 · see citing works
“Within the main MB subgroups, SHH and Group 4 patients have an intermediate prognosis (67–88% 5-year OS [20,21] and can present with primary metastatic dissemination (approx.”
BackgroundInfluentialSelf-citationRestoration of miR-193a expression is tumor-suppressive in MYC amplified Group 3 medulloblastoma
Bharambe, H. S., Joshi, A. A., Yogi, K., Kazi, S., & Shirsat, N. V. (2020) · Acta Neuropathologica Communications · doi:10.1186/s40478-020-00942-5 · Cited by 12 · see citing works
Ljungblad, L. M., Bergqvist, F., Tümmler, C., Madawala, S. R. P., Olsen, T. K., Andonova, T., Jakobsson, P., Johnsen, J. I., Picková, J., Strandvik, B., et al. (2022) · Life Sciences · doi:10.1016/j.lfs.2022.120394 · Cited by 12 · see citing works
Korshunov, A., Okonechnikov, K., Stichel, D., Schrimpf, D., Delaidelli, A., Tonn, S., Mynarek, M., Sievers, P., Sahm, F., Jones, D., et al. (2022) · Acta Neuropathologica · doi:10.1007/s00401-022-02460-1 · Cited by 12 · see citing works
“The Grp 3 MB molecular group was confirmed using t-distributed stochastic neighbor embedding (t-SNE) and uniform manifold approximation and projection for dimension reduction (UMAP) methods as described [13, 16, 21].”
BackgroundMethodSelf-citationWerbowetski‐Ogilvie, T. E. (2021) · FEBS Journal · doi:10.1111/febs.15817 · Cited by 13 · see citing works
Kim, J. W., Park, S., Choi, S. A., Kim, S., Koh, E. J., Won, J., Nam, S. M., & Phi, J. H. (2022) · BMC Cancer · doi:10.1186/s12885-022-10328-6 · Cited by 12 · see citing works
“but assuming that those two cases out of eight (25%) in the SHH group were TP53 mutant, the proportion of TP53 mutations in our cohort does not seem significantly high compared figures in the literature [24, 27].”
BackgroundResultInfluentialGuerin, J. B., Kaufmann, T. J., Eckel, L. J., Morris, J. M., Vaubel, R. A., Giannini, C., & Johnson, D. R. (2023) · Radiology · doi:10.1148/radiol.221885 · Cited by 12 · see citing works
Decoding the Roles of Astrocytes and Hedgehog Signaling in Medulloblastoma
Duarte, T. T., Teixeira, S. A., Gonzalez‐Reyes, L. E., & Reis, R. M. (2021) · Current Oncology · doi:10.3390/curroncol28040267 · Cited by 10 · see citing works
Group-specific cellular metabolism in Medulloblastoma
Funke, V. L. E., Walter, C., Melcher, V., Wei, L., Sandmann, S., Hotfilder, M., Varghese, J., Jäger, N., Kool, M., Jones, D., et al. (2023) · Journal of Translational Medicine · doi:10.1186/s12967-023-04211-6 · Cited by 11 · see citing works
“While molecular risk stratification has significantly improved our understanding of MB, it is not yet fully elucidated what drives heterogeneity and gradients, especially among G3/G4 MB [2, 6].”
BackgroundSelf-citationCREB signaling activity correlates with differentiation and survival in medulloblastoma
Armandari, I., Zomerman, W. W., Plasschaert, S. L. A., Smit, M. J., Martini, T. E. I., Magalhães, E. S. D. C., Hogeling, S. M., Rozema-Huizinga, G. C., Lourens, H. J., Boer, T. M.-D., et al. (2021) · Scientific Reports · doi:10.1038/s41598-021-95381-0 · Cited by 12 · see citing works
Hourfar, H., Taklifi, P., Razavi, M., & Khorsand, B. (2025) · Clinical Oncology · doi:10.1016/j.clon.2025.103789 · Cited by 10 · see citing works
Angiogenesis and Lymphangiogenesis in Medulloblastoma Development
Penco-Campillo, M., Pagès, G., & Martial, S. (2023) · Biology · doi:10.3390/biology12071028 · Cited by 9 · see citing works
“For instance, the SHH-I (or SHH-β) and SHH-II (or SHH-γ) subtypes are predominantly found in children under the age of two [12].”
BackgroundThe Current Landscape of Targeted Clinical Trials in Non-WNT/Non-SHH Medulloblastoma
Ghasemi, D. R., Fleischhack, G., Milde, T., & Pajtler, K. W. (2022) · Cancers · doi:10.3390/cancers14030679 · Cited by 11 · see citing works
“[8,12] A significant percentage of genomic alterations in these tumors is detected in genes that are involved in chromatin remodeling, histone modification, enhancer hijacking, and other epigenetic regulatory mechanisms, especially in Gr.”
BackgroundBorlase, S., DeCarlo, A., Coudière-Morrison, L., Liang, L., Porter, C. J., Ramaswamy, V., & Werbowetski‐Ogilvie, T. E. (2023) · Cell Death Discovery · doi:10.1038/s41420-023-01646-0 · Cited by 8 · see citing works
“Medulloblastoma (MB) is the most common malignant primary pediatric brain tumor and is highly heterogeneous [1].”
Mapping naturally presented T cell antigens in medulloblastoma based on integrative multi-omics
Velz, J., Freudenmann, L. K., Medici, G., Dubbelaar, M. L., Mohme, M., Ghasemi, D. R., Scheid, J., Kowalewski, D. J., Patterson, A. B., Zeitlberger, A. M., et al. (2025) · Nature Communications · doi:10.1038/s41467-025-56268-0 · Cited by 9 · see citing works
“Integrating molecular subgroups into the WHO classi fi cation highlights the importance of molecular risk strati fi cation in patients with medulloblastomaandcallsfornewtumorsubtype-speci fi ctherapeutic approaches 7 – 9 .”
Min, H.-K., Zhao, H., Bahcheli, A. T., Pan, P., Chan, J., Chen, J., Low, E., Zhou, Y., Wang, X., Bajic, S., et al. (2025) · Nature Biomedical Engineering · doi:10.1038/s41551-025-01487-5 · Cited by 10 · see citing works
“MB comprises four subgroups (SHH, WNT, Group 3 and Group 4), each with distinct cells of origin, genetic mutations, epigenetic features and clinical outcomes 28 .”
Zanotti, S., Vanhauwaert, S., Neste, C. V., Olexiouk, V., Laere, J. V., Verschuuren, M., der Meulen, J. V., Mus, L. M., Durinck, K., Tilleman, L., et al. (2021) · Scientific Reports · doi:10.1038/s41598-021-93863-9 · Cited by 9 · see citing works
Wang, D., Gong, J., Zhang, H., Liu, Y., Sun, N., Hao, X., & Mu, K. (2022) · Diagnostic Pathology · doi:10.1186/s13000-022-01250-3 · Cited by 9 · see citing works
“WNT-activated MB account for about 10% of the total, and most of them are found in children aged 6–10 years which has the highest sensitivity to postoperative chemoradiotherapy, and is the least likely to metastasize [7].”
BackgroundReview of the impact of molecular analysis on the therapy of medulloblastoma
Sarvode, S., & Gajjar, A. J. (2023) · Pediatric Hematology Oncology Journal · doi:10.1016/j.phoj.2023.05.001 · Cited by 9 · see citing works
Overview and recent advances in the targeting of medulloblastoma cancer stem cells
Paul, M. R., & Zage, P. E. (2021) · Expert Review of Anticancer Therapy · doi:10.1080/14737140.2021.1932472 · Cited by 10 · see citing works
Magge, R., Barbaro, M., & Fine, H. A. (2021) · World Neurosurgery · doi:10.1016/j.wneu.2021.02.093 · Cited by 9 · see citing works
Role of mammalian long non-coding RNAs in normal and neuro oncological disorders
Singh, N. (2021) · Genomics · doi:10.1016/j.ygeno.2021.07.015 · Cited by 9 · see citing works
Zhu, X.-Z., Zhang, H.-Y.-L., Zhou, Y.-F., Chen, Y.-Y., Fu, T., Jin, M.-L., Zhao, Y.-X., Xie, Y.-F., Zeng, X., Jin, X., et al. (2025) · Cancer Research · doi:10.1158/0008-5472.can-24-5002 · Cited by 8 · see citing works
Smith, K. S., Dhanda, S. K., Billups, C. A., Sioson, E., Lu, C., Peraza, A. Z., Gangwani, K., Li, Y., Li, Q., Lin, T., et al. (2025) · Neuro-Oncology · doi:10.1093/neuonc/noaf250 · Cited by 8 · see citing works
Self-citationChen, M., Shi, X., Wang, Y., Zhang, J., Guo, J., Guan, X., Sun, Y. L., Wu, W., Li, C., Tian, Y., et al. (2025) · EBioMedicine · doi:10.1016/j.ebiom.2025.106043 · Cited by 8 · see citing works
Conti, V., Cominelli, M., Pieri, V., Gallotti, A. L., Pagano, I., Zanella, M., Mazzoleni, S., Pivetta, F., Patanè, M., Scotti, G. M., et al. (2021) · JCI Insight · doi:10.1172/jci.insight.153462 · Cited by 8 · see citing works
“Although concurrent loss of PTCH1 and TP53 has been found in a few LC/A SHH α human MB (15), our model might not completely reproduce the genetics of the disease, which in most cases is known to be associated with amplification in MYCN and GLI2 (14, 37, 38).”
Influential
- Authors
- Hovestadt, V., Ayrault, O., Swartling, F. J., Robinson, G. W., Pfister, S. M., & Northcott, P. A.
- Affiliations
- Broad Institute (US)
- Université Paris-Sud (FR)
- Uppsala University (SE)
- St. Jude Children's Research Hospital (US)
- German Cancer Research Center (DE)
- Corresponding author
- Northcott, Paul A.
- ORCID
- Venue
- Nature Reviews Cancer
- Published
- 2019-12-09
- Volume
- 20
- Issue
- 1
- Pages
- 42-56
- ISSN
- 1474-175X (ISSN-L)
- 1474-1768
- PMC
- PMC9113832
- OpenAlex
- W2991944835
- Cited by
- 271
- References
- 155
- Citations by year
- 2026: 26 · 2025: 47 · 2024: 44 · 2023: 53 · 2022: 36 · 2021: 45 · 2020: 17 · 2019: 1 · 2013: 1
- FWCI
- 3.07
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Nature reviews. Cancer (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- HAL (submittedVersion, other-oa)
- Funders
- National Cancer Institute (R01CA232143)
- Topics
- Health Sciences › Medicine › Genetics › Glioma Diagnosis and Treatment
- Health Sciences › Medicine › Neurology › Neuroblastoma Research and Treatments
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Cancer Genomics and Diagnostics
- Keywords
- medulloblastoma, molecular subtypes, single-cell profiling, genomic profiling, epigenetic profiling, gene expression profiling, proteomic profiling, tumor heterogeneity, tumor recurrence, pediatric brain tumors, targeted therapy, diagnosis
- MeSH terms
- Animals, Combined Modality Therapy, Disease Susceptibility, Humans, Medulloblastoma, Neoplasm Metastasis, Neoplasm Staging, Prognosis, Recurrence, Biomarkers, Tumor, Treatment Outcome, Disease Management, Genomics, Molecular Diagnostic Techniques, Proteomics, Genetic Association Studies, Epigenomics, Tumor Microenvironment
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