Zusammenfassung
Das Auftreten von Hirntumoren im Kindes- und Jugendalter ist eng mit der Entwicklung des Zentralnervensystems verknüpft, während der viele unterschiedliche Zellpopulationen über einen gewissen Zeitraum anfällig für tumorauslösende Veränderungen sein können. Dies spiegelt sich in der enormen Vielfalt von Tumorarten wider, von denen einige häufiger, andere sehr selten auftreten und die oft eine umschriebene Altersgruppe betreffen. Das Spektrum reicht von benignen, langsam wachsenden bis hin zu hochgradig aggressiven Tumoren. Die Unterscheidung erfolgt bislang hauptsächlich nach dem histopathologischen Erscheinungsbild der Tumorzellen. In vielen dieser Tumorarten finden sich charakteristische genetische und epigenetische Veränderungen, die zunehmend Einzug in die Klassifikation finden, Aussagen über den Krankheitsverlauf zulassen und zielgerichtete Therapiestrategien ermöglichen. Die derzeitige Behandlung besteht in den meisten Fällen in der operativen Tumorentfernung und einer Kombination von adjuvanter Strahlen- und Chemotherapie.
Similar content being viewed by others
Literatur
Biegel JA, Zhou JY, Rorke LB, Stenstrom C, Wainwright LM, Fogelgren B (1999) Germ-line and acquired mutations of INI1 in atypical teratoid and rhabdoid tumors. Cancer Res 59:74–79
Cage TA, Clark AJ, Aranda D, Gupta N, Sun PP, Parsa AT, Auguste KI (2013) A systematic review of treatment outcomes in pediatric patients with intracranial ependymomas. J Neurosurg Pediat 11:673–681
Ellison DW, Kocak M, Dalton J, Megahed H, Lusher ME, Ryan SL, Zhao W, Nicholson SL, Taylor RE, Bailey S et al. (2011) Definition of disease-risk stratification groups in childhood medulloblastoma using combined clinical pathologic and molecular variables. J Clin Oncol 29:1400–1407
Gajjar AJ, Robinson GW (2014) Medulloblastoma-translating discoveries from the bench to the bedside. Nat Rev Clin Oncol 11:714–722
Gajjar A, Stewart CF, Ellison DW, Kaste S, Kun LE, Packer RJ, Goldman S, Chintagumpala M, Wallace D, Takebe N et al. (2013) Phase I study of vismodegib in children with recurrent or refractory medulloblastoma: a pediatric brain tumor consortium study. Clin Cancer Res 19:6305–6312
Gajjar A, Bowers DC, Karajannis MA, Leary S, Witt H, Gottardo NG (2015) Pediatric Brain Tumors: Innovative Genomic Information Is Transforming the Diagnostic and Clinical Landscape. J Clin Oncol 33:2986–2998
Jones DT, Jager N, Kool M, Zichner T, Hutter B, Sultan M, Cho YJ, Pugh TJ, Hovestadt V, Stutz AM et al. (2012) Dissecting the genomic complexity underlying medulloblastoma. Nature 488:100–105
Jones DT, Hutter B, Jager N, Korshunov A, Kool M, Warnatz HJ, Zichner T, Lambert SR, Ryzhova M, Quang DA et al. (2013) Recurrent somatic alterations of FGFR1 and NTRK2 in pilocytic astrocytoma. Nat Genet 45:927–932
Judkins AR, Mauger J, Ht, A, Rorke LB, Biegel JA (2004) Immunohistochemical analysis of hSNF5/INI1 in pediatric CNS neoplasms. Am J Surg Pathol 28:644–650
Kilday JP, Mitra B, Domerg C, Ward J, Andreiuolo F, Osteso-Ibanez T, Mauguen A, Varlet P, Le Deley MC, Lowe J et al. (2012) Copy number gain of 1q25 predicts poor progression-free survival for pediatric intracranial ependymomas and enables patient risk stratification: a prospective European clinical trial cohort analysis on behalf of the Children's Cancer Leukaemia Group (CCLG), Societe Francaise d'Oncologie Pediatrique (SFOP), and International Society for Pediatric Oncology (SIOP). Clin Cancer Res 18:2001–2011
Kool M, Jones DT, Jager N, Northcott PA, Pugh TJ, Hovestadt V, Piro RM, Esparza LA, Markant SL, Remke M et al. (2014) Genome sequencing of SHH medulloblastoma predicts genotype-related response to smoothened inhibition. Cancer Cell 25:393–405
Korshunov A, Witt H, Hielscher T, Benner A, Remke M, Ryzhova M, Milde T, Bender S, Wittmann A, Schottler A et al. (2010) Molecular staging of intracranial ependymoma in children and adults. J Clin Oncol 28:3182–3190
Korshunov A, Sturm D, Ryzhova M, Hovestadt V, Gessi M, Jones DT, Remke M, Northcott P, Perry A, Picard D et al. (2014) Embryonal tumor with abundant neuropil and true rosettes (ETANTR), ependymoblastoma and medulloepithelioma share molecular similarity and comprise a single clinicopathological entity. Acta Neuropathol 128:279–289
Louis DN, Ohgaki H, Wiestler OD, Cavenee WK (2016) WHO Classification of tumors of the central nervous system. IARC, Lyon
Mack SC, Witt H, Piro RM, Gu, L, Zuyderduyn S, Stutz AM, Wang X, Gallo M, Garzia L, Zayne K et al. (2014) Epigenomic alterations define lethal CIMP-positive ependymomas of infancy. Nature 506:445–450
Merchant TE, Li, C, Xiong X, Kun LE, Boop FA, Sanford RA (2009) Conformal radiotherapy after surgery for paediatric ependymoma: a prospective study. The Lancet Oncology 10:258–266
Morfouace M, Shelat A, Jacus M, Freeman BB, 3rd, Turner D, Robinson S, Zindy F, Wang YD, Finkelstein D, Ayrault O et al. (2014) Pemetrexed and gemcitabine as combination therapy for the treatment of Group3 medulloblastoma. Cancer cell 25:516–529
Northcott PA, Lee C, Zichner T, Stutz AM, Erkek S, Kawauchi D, Shih DJ, Hovestadt V, Zapatka M, Sturm D et al. (2014) Enhancer hijacking activates GFI1 family oncogenes in medulloblastoma. Nature 511:428–434
Northcott PA, Pfister SM, Jones DT (2015) Next-generation (epi)genetic drivers of childhood brain tumours and the outlook for targeted therapies. Lancet Oncol 16:e293–302
Ostrom QT, Gittleman H, Xu J, Kromer C, Wolinsky Y, Kruchko C, Barnholtz-Sloan JS (2016) CBTRUS Statistical Report: Primary Brain and Other Central Nervous System Tumors Diagnosed in the United States in 2009–2013. Neuro Oncol 18 (Suppl 5): v1–v75. https://doi.org/10.1093/neuonc/now207
Pajtler KW, Witt H, Sill M, Jones DT, Hovestadt V, Kratochwil F, Wani K, Tatevossian R, Punchihewa C, Johann P et al. (2015) Molecular Classification of Ependymal Tumors across All CNS Compartments Histopathological Grades and Age Groups. Cancer Cell 27:728–743
Parker M, Mohankumar KM, Punchihewa C, Weinlich R, Dalton JD, Li, Y, Lee R, Tatevossian RG, Phoenix TN, Thiruvenkatam R et al. (2014) C11orf95–RELA fusions drive oncogenic NF-kappaB signalling in ependymoma. Nature 506:451–455
Pejavar S, Polley MY, Rosenberg-Wohl S, Chennupati S, Prados MD, Berger MS, Banerjee A, Gupta N, Haas-Kogan D (2012) Pediatric intracranial ependymoma: the roles of surgery radiation and chemotherapy. J Neurooncol 106:367–375
Purdy E, Johnston DL, Bartels U, Fryer C, Carret AS, Crooks B, Eisenstat DD, Lafay-Cousin L, Larouche V, Wilson B et al. (2014) Ependymoma in children under the age of 3 years: a report from the Canadian Pediatric Brain Tumour Consortium. J Neurooncol 117:359–364
Rausch T, Jones DT, Zapatka M, Stutz AM, Zichner T, Weischenfeldt J, Jager N, Remke M, Shih D, Northcott PA et al. (2012) Genome sequencing of pediatric medulloblastoma links catastrophic DNA rearrangements with TP53 mutations. Cell 148:59–71
Rudin CM, Hann CL, Laterra J, Yauch RL, Callahan CA, Fu, L, Holcomb T, Stinson J, Gould SE, Coleman B et al. (2009) Treatment of medulloblastoma with hedgehog pathway inhibitor GDC-0449. N Engl J Med 361:1173–1178
Schwartzentruber J, Korshunov A, Liu XY, Jones DTW Pfaff E, Jacob K, Sturm D, Fontebasso AM, Quang DA, Tonjes M et al. (2012) Driver mutations in histone H3.3 and chromatin remodelling genes in paediatric glioblastoma. Nature 482:226–231
Sturm D, Witt H, Hovestadt V, Khuong-Quang DA, Jones DT, Konermann C, Pfaff E, Tonjes M, Sill M, Bender S et al. (2012) Hotspot mutations in H3F3A and IDH1 define distinct epigenetic and biological subgroups of glioblastoma. Cancer Cell 22:425–437
Sturm D, Orr BA, Toprak UH, Hovestadt V, Jones DTW Capper D, Sill M, Buchhalter I, Northcott PA, Leis I et al. (2016) New Brain Tumor Entities Emerge from Molecular Classification of CNS-PNETs. Cell 164(5):1060–1072
Taylor MD, Northcott PA, Korshunov A, Remke M, Cho YJ, Clifford SC, Eberhart CG, Parsons DW, Rutkowski S, Gajjar A et al. (2012) Molecular subgroups of medulloblastoma: the current consensus. Acta Neuropathol123:465–472
Versteege I, Sevenet N, Lange J, Rousseau-Merck MF, Ambros P, Handgretinger R, Aurias A, Delattre O (1998) Truncating mutations of hSNF5/INI1 in aggressive paediatric cancer. Nature 394:203–206
Witt H, Mack SC, Ryzhova M, Bender S, Sill M, Isserlin R, Benner A, Hielscher T, Milde T, Remke M et al. (2011) Delineation of two clinically and molecularly distinct subgroups of posterior fossa ependymoma. Cancer Cell 20:143–157
Wu, G, Broniscer A, McEachron TA, Lu, C, Paugh BS, Becksfort J, Qu, C, Ding L, Huether R, Parker M et al. (2012) Somatic histone H3 alterations in pediatric diffuse intrinsic pontine gliomas and non-brainstem glioblastomas. Nat Genet 44(3):251–253
Zhang J, Wu, G, Miller CP, Tatevossian RG, Dalton JD, Tang B, Orisme W, Punchihewa C, Parker M, Qaddoumi I et al. (2013) Whole-genome sequencing identifies genetic alterations in pediatric low-grade gliomas. Nat Genet 45:602–612
Author information
Authors and Affiliations
Corresponding author
Editor information
Editors and Affiliations
Rights and permissions
Copyright information
© 2018 Springer-Verlag Berlin Heidelberg
About this chapter
Cite this chapter
Sturm, D., Pfister, S.M., Witt, H. (2018). Onkologische Grundlagen und Molekulargenetik von ZNS-Tumoren im Kindes- und Jugendalter. In: Bächli, H., Lütschg, J., Messing-Jünger, M. (eds) Pädiatrische Neurochirurgie. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-662-48700-6_32
Download citation
DOI: https://doi.org/10.1007/978-3-662-48700-6_32
Published:
Publisher Name: Springer, Berlin, Heidelberg
Print ISBN: 978-3-662-48699-3
Online ISBN: 978-3-662-48700-6
eBook Packages: Medicine (German Language)