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Abstract
Medulloblastoma is more frequent central nervous system malignancy in childhood. It is characterized by wide range of clinical heterogeneity, response to therapy and outcome. Many authors demonstrated prognostic significance of clinical, morphological, cytogenetic and molecular-biological features of the tumor. Implementation of high-throughput molecular-genetic techniques allows the medulloblastoma patients discrimination into 4 independent subgroups with distinct source of histogenesis, molecular pathogenesis, clinical manifestation and outcome. This review is devoted to molecular-biological features of medulloblastoma, underlying its clinical heterogeneity and forming the basis for individualized risk adapted and targeted treatment.References
Beachy P.A., Hymowitz S.G., Lazarus R.A. et al. Interactions between Hedgehog proteins and their binding partners come into view // Genes. Dev. - 2010. - Vol. 24. - № 18. - P. 2001-2012.
Belkina A.C., Denis G.V. BET domain co-regulators in obesity, inflammation and cancer // Nat. Rev. Cancer. - 2012. - Vol. 12. - № 7. - P. 465-477.
Briscoe J., Therond P.P. The mechanisms of Hedgehog signalling and its roles in development and disease // Nat. Rev. Mol. Cell. Biol. - 2013. - Vol. 14. - № 7. - P. 416-429.
Cadigan K.M. TCFs and Wnt/p-catenin signaling: more than one way to throw the switch // Curr. Top. Dev. Biol. - 2012. - Vol. 98. - P. 1-34.
Chen H.J., Hsu L.S., Shia YT. et al. The p-catenin/TCF complex as a novel target of resveratrol in the Wnt/pcatenin signaling pathway // Biochem Pharmacol. - 2012. - Vol. 84. - №. 9. - P. 1143-1153.
Cimmino F, Scoppettuolo M.N., Carotenuto M. et al. Nor-cantharidin impairs medulloblastoma growth by inhibition of Wnt/-catenin signaling // J. Neurooncol. - 2012. - Vol. 106. - № 1. - P. 59-70.
Clifford S.C., Lusher M.E., Lindsey J.C. et al. Wnt/Wingless pathway activation and chromosome 6 loss characterize a distinct molecular sub-group of medulloblasto-mas associated with a favorable prognosis // Cell Cycle. - 2006. - Vol. 5. - №. 22. - P. 2666-2670.
Clifford S.C., Lannering B., Schwalbe E.C. et al. Biomarker-driven stratification of disease-risk in non-metastatic medulloblastoma: Results from the multi-center HIT-SIOP-PNET4 clinical trial // Oncotarget. - 2015. - Vol. 6. - № 36. - P. 38827-38839.
Coluccia D., Figuereido C., Isik S. et al. Medulloblastoma: Tumor Biology and Relevance to Treatment and Prognosis Paradigm // Curr Neurol Neurosci Rep. - 2016. - Vol. 16. - № 5. - P. 43-54.
Cruciat C.M., Dolde C., de Groot R.E. et al. RNA helicase DDX3 is a regulatory subunit of casein kinase 1 in Wnt-p-catenin signaling // Science. - 2013. - Vol. 339. - № 6126. - P. 1436-1441.
Dhall G. Medulloblastoma // J. Child Neurol. - 2009. -Vol. 24. - № 11. - P. 1418-1430.
Ellison D.W., Onilude O.E., Lindsey J.C. et al. beta-Catenin status predicts a favorable outcome in childhood medul-loblastoma: the United Kingdom Children's Cancer Study Group Brain Tumour Committee // J. Clin. Oncol. - 2005. - Vol. 23. - № 31. - P. 7951-7957.
Ellison D.W., Dalton J., Kocak M. et al. Medulloblastoma: clinicopathological correlates of SHH, WNT, and nonSHH/WNT molecular subgroups // Acta. Neuropathol. - 2011. - Vol. 121. - № 3. - P. 381-396.
Ellison D.W., Kocak M., Dalton J. et al. Definition of dis-ease-risk stratification groups in childhood medulloblas-toma using combined clinical, pathologic, and molecular variables // J. Clin. Oncol. - 2011. - Vol. 29. - № 11. - P. 400-407.
Evans G., Burnell L., Campbell R. et al.Congenital anomalies and genetic syndromes in 173 cases of medulloblastoma // Med. Pediatr. Oncol. - 1993. - Vol. 21. - № 6. - P. 433-434.
Falkenstein K.N., Vokes S.A. Transcriptional regulation of graded Hedgehog signaling // Semin. Cell Dev. Biol. - 2014. - № 33. - P. 73-80.
Gajjar A., Hernan R., Kocak M. et al. Clinical, histopathologic, and molecular markers of prognosis: toward a new disease risk stratification system for medulloblastoma // J. Clin. Oncol. - 2004. - Vol. 22. - № 6. - P. 984-993.
Gajjar A., Chintagumpala M., Ashley D. et al. Risk-adapted craniospinal radiotherapy followed by high-dose chemotherapy and stem-cell rescue in children with newly diagnosed medulloblastoma (St Jude Medulloblastoma-96): long-term results from a prospective, multicentre trial // Lancet Oncol. - 2006. - Vol. 7. - № 10. - P. 813-820.
Gajjar A., Stewart C.F, Ellison D.W. et al. Phase I study of vismodegib in children with recurrent or refractory me-dulloblastoma: a pediatric brain tumor consortium study // Clin. Cancer Res. - 2013. - Vol. 19. - № 22. - P. 6305-6312.
Gajjar A.J., Robinson G.W. Medulloblastoma-translating discoveries from the bench to the bedside // Nat. Rev. Clin. Oncol. - 2014. - Vol. 11. - № 12. - P. 714-722.
Gajjar A., Bowers D.C., Karajannis M.A. et al. Pediatric Brain Tumors: Innovative Genomic Information Is Transforming the Diagnostic and Clinical Landscape // J. Clin. Oncol. - 2015. - Vol. 33. - № 27. - P. 2986-2998.
Gibson P., Tong Y, Robinson G. et al. Subtypes of medulloblastoma have distinct developmental origins // Nature. - 2010. - Vol. 468. - № 7327. - P. 1095-1099.
Geiss G.K., Bumgarner R.E., Birditt B. et al. Direct multiplexed measurement of gene expression with color-coded probe pairs // Nat. Biotechnol. - 2008. - Vol. 26. - № 3. - P. 317-325.
Gilbertson R.J., Perry R.H., Kelly P.J. et al. Prognostic significance of HER2 and HER4 coexpression in childhood medulloblastoma // Cancer Res. - 1997. - Vol. 57. - № 15. - P. 3272-3280.
Gilbertson R., Wickramasinghe C., Hernan R. et al. Clinical and molecular stratification of disease risk in medul-loblastoma // Br. J. Cancer. - 2001. - Vol. 85. - № 5. - P. 705-712.
Gougelet A., Colnot S. A Complex Interplay between Wnt/ p-Catenin Signalling and the Cell Cycle in the Adult Liver // Int. J. Hepatol. - 2012. - Vol. 2012. - P. 1-7.
Grotzer M.A., Janss A.J., Phillips PC., Trojanowski J.Q. Neurotrophin receptor TrkC predicts good clinical outcome in medulloblastoma and other primitive neuroectodermal brain tumors // Klin. Padiatr. - 2000. - Vol. 212. - № 4. - P. 196-199.
Grotzer M.A., Hogart M.D., Janss A.J. et al. MYC messenger RNA expression predicts survival outcome in childhood primitive neuroectodermal tumor/medulloblastoma // Clin. Cancer Res. - 2001. - Vol. 7. - № 8. - P 24252433.
Hadjihannas M.V., Bernkopf D.B., Bruckner M., Behrens J. Cell cycle control of Wnt/p-catenin signalling by conductin/axin2 through CDC20 // EMBO Rep. - 2012. - Vol.13. - № 4. - P. 347-354.
Hamilton S.R., Liu B., Parsons R.E. et al.The molecular basis of Turcot's syndrome // N. Engl. J. Med. - 1995. - Vol. 332. - № 13. - P. 839-847.
Hovestadt V., Remke M., Kool M. et al. Robust molecular subgrouping and copy-number profiling of medulloblasto-ma from small amounts of archival tumour material using high-density DNA methylation arrays // Acta Neuropathol. - 2013. - Vol. 125. - № 6. - P. 913-916.
Hui C.C., Angers S. Gli proteins in development and disease // Annu. Rev. Cell Dev. Biol. - 2011. - Vol. 27. - P. 513-537.
Jones D.T., Jager N., Kool M. et al. Dissecting the genomic complexity underlying medulloblastoma // Nature. - 2012. - Vol. 488. - № 7409. - P. 100-105.
Jozwiak J., Grajkowska W., Wlodarski P. Pathogenesis of medulloblastoma and current treatment outlook // Med. Res. Rev. - 2007. - Vol. 27. - № 6. - P. 869-890.
Komiya Y, Habas R. Wnt signal transduction pathways // Organogenesis. - 2008. - Vol. 4. - № 2. - P. 68-75.
Kool M., Korshunov A., Remke M. et al. Molecular subgroups of medulloblastoma: an international meta-analysis of transcriptome, genetic aberrations, and clinical data of WNT, SHH, Group 3, and Group 4 medulloblastomas // Acta. Neuropathol. - 2012. - Vol. 123. - № 4. - P. 473-484.
Kool M., Korshunov A., Pfister S.M. Update on molecular and genetic alterations in adult medulloblastoma // Memo. - 2012. - Vol. 5. - № 3. - P. 228-232.
Kool M., Jones D.T., Jageret N. al. Genome sequencing of SHH medulloblastoma predicts genotype-related response to smoothened inhibition // Cancer Cell. - 2014. - Vol. 25. - № 3. - P. 393-405.
Lee M.J., Hatton B.A., Villavicencio E.H. et al. Hedgehog pathway inhibitor saridegib (IPI-926) increases lifespan in a mouse medulloblastoma model // Proc. Natl. Acad. Sci. USA. - 2012. - Vol. 109. - № 20. - P. 7859-7864.
Lin C.Y, Erkek S., Tong Y et al. Active medulloblastoma enhancers reveal subgroup-specific cellular origins // Nature. - 2016. - Vol. 530. - № 7588. - P. 57-62.
Louis D.N., Ohgaki H., Wiestler O.D. et al. The 2007 WHO classification of tumours of the central nervous system // Acta. Neuropathol. - 2007. - Vol. 114. - № 2. - P. 97-109.
Louis D.N., Perry A., Reifenberger G. et al. The 2016 World Health Organization classification of tumors of the central nervous system: a summary // Acta Neuropathol. - 2016. - Vol. 131. - № 6. - P. 803-820.
Millard N.E., De Braganca K.C. Medulloblastoma // J. Child Neurol. - 2015. - Vol. 2. - P. 1-13.
Minde D.P., Anvarian Z., Rudiger S.G., Maurice M.M. Messing up disorder: how do missense mutations in the tumor suppressor protein APC lead to cancer? // Mol. Cancer. - 2011. - Vol. 10. - P. 101-110.
Ng J.M., Curran T. The Hedgehog's tale: developing strategies for targeting cancer // Nat. Rev. Cancer. - 2011. - Vol. 11. - № 7. - P. 493-501.
Niehrs C. The complex world of WNT receptor signaling // Nat. Rev. Mol. Cell Biol. - 2012. - Vol. 13. - № 12. - P. 767-79.
Northcott P.A., Nakahara Y, Wu X. et al. Multiple recurrent genetic events converge on control of histone lysine methylation in medulloblastoma // Nat Genet. - 2009. -Vol. 41. - № 4. - P. 465-472.
Northcott P.A., Korshunov A., Witt H. et al. Medulloblastoma comprises four distinct molecular variants // J. Clin. Oncol. - 2011. - Vol. 29. -№ 11. - P. 1408-1414.
Northcott P.A., Jones D.T., Kool M. et al. Medulloblastomics: the end of the beginning // Nat. Rev. Cancer. - 2012. -Vol. 12. - № 12. - P. 818-834.
Northcott P.A., Korshunov A., Pfister S.M., Taylor M.D. The clinical implications of medulloblastoma subgroups // Nat. Rev. Neurol. - 2012. - Vol. 8. - № 6. - P. 340-351.
Northcott P.A., Shih D.J., Remke M. et al. Rapid, reliable, and reproducible molecular sub-grouping of clinical medulloblastoma samples // Acta Neuropathol. - 2012. - Vol. 123. - № 4. - P. 615-626.
Northcott P.A., Shih D.J., Peacock J. et al. Subgroup-specific structural variation across 1,000 medulloblastoma genomes // Nature. - 2012. - Vol. 488. - № 7409. - P. 49-56.
Northcott P.A., Lee C., Zichner T., Sttz A.M. et al. Enhancer hijacking activates GFI1 family oncogenes in medulloblastoma // Nature. - 2014. - Vol. 511. - № 7510. - P. 428-434.
Ostrom Q.T., de Blank P.M., Kruchko C. et al.c Alex's Lemonade Stand Foundation Infant and Childhood Primary Brain and Central Nervous System Tumors Diagnosed in the United States in 2007-2011 // Neuro Oncol. - 2015. - Vol. Suppl. 10. - P. 1-36.
Pan E., Pellarin M., Holmes E. et al. Isochromosome 17q is a negative prognostic factor in poor-risk childhood medulloblastoma patients // Clin. Cancer Res. - 2005. -Vol. 11. - № 13. - P. 4733-4740.
Pfister S., Remke M., Benner A. et al. Outcome prediction in pediatric medulloblastoma based on DNA copy-number aberrations of chromosomes 6q and 17q and the MYC and MYCN loci // J. Clin. Oncol. - 2009. - Vol. 27. - № 10. - P. 1627-1636.
Pietsch T., Schmidt R., Remke M. et al. Prognostic significance of clinical, histopathological, and molecular characteristics of medulloblastomas in the prospective HIT2000 multicenter clinical trial cohort // Acta Neuropathol. - 2014. - Vol. 128. - № 1. - P. 137-149.
Pugh T.J., Weeraratne S.D., Archer T.C. et al. Medulloblastoma exome sequencing uncovers subtype-specific somatic mutations // Nature. - 2012. - Vol. 488. - № 7409. - P. 106-110.
Ransohoff K.J., Sarin K.Y, Tang J.Y Smoothened Inhibitors in Sonic Hedgehog Subgroup Medulloblastoma // J. Clin. Oncol. - 2015. - Vol. 33. - № 24. - P. 2692-2694.
Ray A., Ho M., Ma J. et al. A clinicobiological model predicting survival in medulloblastoma // Clin. Cancer Res. - 2004. - Vol. 10. - № 22. - P. 7613-7620.
Remke M., Hielscher T, Korshunov A. et al. FSTL5 is a marker of poor prognosis in non-WNT/non-SHH medulloblastoma // J. Clin. Oncol. - 2011. - Vol. 29. -№ 29. - P. 3852-3861.
Robinson G., Parker M., Kranenburg T.A. et al. Novel mutations target distinct subgroups of medulloblastoma // Nature. - 2012. - Vol. 488. - № 7409. - P. 43-48.
Robinson G.W., Orr B.A., Wu G. et al. Vismodegib Exerts Targeted Efficacy Against Recurrent Sonic Hedgehog-Subgroup Medulloblastoma: Results From Phase II Pediatric Brain Tumor Consortium Studies PBTC-025B and PBTC-032 // J. Clin. Oncol. - 2015. - Vol. 33. - № 24. - P. 2646-2654.
Rutkowski S., Bode U., Deinlein F. et al. Treatment of early childhood medulloblastoma by postoperative chemotherapy alone // N. Engl. J. Med. - 2005. - Vol. 352. - № 10. - P. 978-986.
Sekulic A., Migden M.R., Oro A.E. et al. Efficacy and safety of vismodegib in advanced basal-cell carcinoma // N. Engl. J. Med. - 2012. - Vol. 366. - № 23. - P. 2171-2179.
Shih D.J., Northcott P.A., Remke M. et al. Cytogenetic prognostication within medulloblastoma subgroups // J. Clin. Oncol. - 2014. - Vol. 32. - № 9. - P. 886-896.
Slade I., Murray A., Hanks S. et al. Heterogeneity of familial medulloblastoma and contribution of germline PTCH1 and SUFU mutations to sporadic medulloblastoma // Fam. Cancer. - 2011. - Vol. 10. - № 2. - P. 337-342.
Tang Y, Gholamin S., Schubert S. et al. Epigenetic targeting of Hedgehog pathway transcriptional output through BET bromodomain inhibition // Nat. Med. - 2014. - Vol. 20. - № 7. - P. 732-740.
Taylor M.D., Mainprize T.G., Rutka J.T. Molecular insight into medulloblastoma and central nervous system primitive neuroectodermal tumor biology from hereditary syndromes: a review // Neurosurgery. - 2000. - Vol. 47. - № 4. - P. 888-901.
Taylor M.D., Liu L., Raffel C. et al. Mutations in SUFU predispose to medulloblastoma // Nat. Genet. - 2002. -Vol. 31. - № 3. - P. 306-310.
Taylor M.D., Northcott P.A., Korshunov A. et al. Molecular subgroups of medulloblastoma: the current consensus // Acta. Neuropathol. - 2012. - Vol. 123. - № 4. - P. 465472.
Teglund S., Toftg rd R. Hedgehog beyond medulloblastoma and basal cell carcinoma // Biochim. Biophys. Acta. -2010. - Vol. 1805. - № 2. - P. 181-208.
Thompson E.M., Whitney N.L., Wu YJ., Neuwelt E.A. The effect of alpha-v integrin inhibition on the malignant characteristics of medulloblastoma // J. Neurosurg. Pediatr. - 2013. - Vol. 11. - № 1. - P. 60-67.
Wilson C.W., Chuang P.T. Mechanism and evolution of cytosolic Hedgehog signal transduction // Development. - 2010. - Vol. 137. - № 13. - P. 2079-2094.
Zhukova N., Ramaswamy V., Remke M. et al. Subgroup-specific prognostic implications of TP53 mutation in medulloblastoma // J. Clin. Oncol. - 2013. - Vol. 31. -№ 23. - P. 2927-2935.
Zinke J., Schneider F.T., Harter P.N. et al. p-Catenin-Gli1 interaction regulates proliferation and tumor growth in medulloblastoma // Mol Cancer. - 2015. - Vol. 14. - № 1. - P. 17-26.
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