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Cell and Tissue Research

, Volume 372, Issue 2, pp 211–221 | Cite as

Origin and initiation mechanisms of neuroblastoma

Review

Abstract

Neuroblastoma is an embryonal malignancy that affects normal development of the adrenal medulla and paravertebral sympathetic ganglia in early childhood. Extensive studies have revealed the molecular characteristics of human neuroblastomas, including abnormalities at genome, epigenome and transcriptome levels. However, neuroblastoma initiation mechanisms and even its origin are long-standing mysteries. In this review article, we summarize the current knowledge about normal development of putative neuroblastoma sources, namely sympathoadrenal lineage of neural crest cells and Schwann cell precursors that were recently identified as the source of adrenal chromaffin cells. A plausible origin of enigmatic stage 4S neuroblastoma is also discussed. With regard to the initiation mechanisms, we review genetic abnormalities in neuroblastomas and their possible association to initiation mechanisms. We also summarize evidences of neuroblastoma initiation observed in genetically engineered animal models, in which epigenetic alterations were involved, including transcriptomic upregulation by N-Myc and downregulation by polycomb repressive complex 2. Finally, several in vitro experimental methods are proposed that hopefully will accelerate our comprehension of neuroblastoma initiation. Thus, this review summarizes the state-of-the-art knowledge about the mechanisms of neuroblastoma initiation, which is critical for developing new strategies to cure children with neuroblastoma.

Keywords

Neuroblastoma Neural crest cells Schwann cell precursors Sympathoadrenal progenitors MYCN 

Notes

Funding information

S. Tsubota was supported by a Grant-in-Aid for JSPS Research Fellow (14 J00157). K. Kadomatsu was supported by grants for the Practical Research for Innovative Cancer Control from Japan Agency for Medical Research and Development (16ck0106011h0003), JSPS KAKENHI Grant Number JP15k15079, and CREST, JST (15656320).

Compliance with ethical standards

Conflict of interest

The authors declare that they have no conflicts of interest.

References

  1. Bate-Eya LT, Ebus ME, Koster J, den Hartog IJ, Zwijnenburg DA, Schild L, van der Ploeg I, Dolman ME, Caron HN, Versteeg R, Molenaar JJ (2014) Newly-derived neuroblastoma cell lines propagated in serum-free media recapitulate the genotype and phenotype of primary neuroblastoma tumours. Eur J Cancer 50:628–637CrossRefPubMedGoogle Scholar
  2. Benard J, Raguenez G, Kauffmann A, Valent A, Ripoche H, Joulin V, Job B, Danglot G, Cantais S, Robert T, Terrier-Lacombe MJ, Chassevent A, Koscielny S, Fischer M, Berthold F, Lipinski M, Tursz T, Dessen P, Lazar V, Valteau-Couanet D (2008) MYCN-non-amplified metastatic neuroblastoma with good prognosis and spontaneous regression: a molecular portrait of stage 4S. Mol Oncol 2:261–271CrossRefPubMedPubMedCentralGoogle Scholar
  3. Ben-Porath I, Thomson MW, Carey VJ, Ge R, Bell GW, Regev A, Weinberg RA (2008) An embryonic stem cell-like gene expression signature in poorly differentiated aggressive human tumors. Nat Genet 40:499–507CrossRefPubMedPubMedCentralGoogle Scholar
  4. Berry T, Luther W, Bhatnagar N, Jamin Y, Poon E, Sanda T, Pei D, Sharma B, Vetharoy WR, Hallsworth A, Ahmad Z, Barker K, Moreau L, Webber H, Wang W, Liu Q, Perez-Atayde A, Rodig S, Cheung NK, Raynaud F, Hallberg B, Robinson SP, Gray NS, Pearson AD, Eccles SA, Chesler L, George RE (2012) The ALK(F1174L) mutation potentiates the oncogenic activity of MYCN in neuroblastoma. Cancer Cell 22:117–130CrossRefPubMedPubMedCentralGoogle Scholar
  5. Boeva V, Louis-Brennetot C, Peltier A, Durand S, Pierre-Eugene C, Raynal V, Etchevers HC, Thomas S, Lermine A, Daudigeos-Dubus E, Geoerger B, Orth MF, Grunewald TGP, Diaz E, Ducos B, Surdez D, Carcaboso AM, Medvedeva I, Deller T, Combaret V, Lapouble E, Pierron G, Grossetete-Lalami S, Baulande S, Schleiermacher G, Barillot E, Rohrer H, Delattre O, Janoueix-Lerosey I (2017) Heterogeneity of neuroblastoma cell identity defined by transcriptional circuitries. Nat Genet 49:1408–1413CrossRefPubMedGoogle Scholar
  6. Brisse HJ, Blanc T, Schleiermacher G, Mosseri V, Philippe-Chomette P, Janoueix-Lerosey I, Pierron G, Lapouble E, Peuchmaur M, Freneaux P, Galmiche L, Algret N, Peycelon M, Michon J, Delattre O, Sarnacki S (2017) Radiogenomics of neuroblastomas: relationships between imaging phenotypes, tumor genomic profile and survival. PLoS One 12:e0185190CrossRefPubMedPubMedCentralGoogle Scholar
  7. Brodeur GM, Bagatell R (2014) Mechanisms of neuroblastoma regression. Nat Rev Clin Oncol 11:704–713CrossRefPubMedPubMedCentralGoogle Scholar
  8. Callahan T, Young HM, Anderson RB, Enomoto H, Anderson CR (2008) Development of satellite glia in mouse sympathetic ganglia: GDNF and GFR alpha 1 are not essential. Glia 56:1428–1437CrossRefPubMedGoogle Scholar
  9. Cazes A, Lopez-Delisle L, Tsarovina K, Pierre-Eugene C, De Preter K, Peuchmaur M, Nicolas A, Provost C, Louis-Brennetot C, Daveau R, Kumps C, Cascone I, Schleiermacher G, Prignon A, Speleman F, Rohrer H, Delattre O, Janoueix-Lerosey I (2014) Activated Alk triggers prolonged neurogenesis and Ret upregulation providing a therapeutic target in ALK-mutated neuroblastoma. Oncotarget 5:2688–2702CrossRefPubMedPubMedCentralGoogle Scholar
  10. Chen Y, Takita J, Choi YL, Kato M, Ohira M, Sanada M, Wang L, Soda M, Kikuchi A, Igarashi T, Nakagawara A, Hayashi Y, Mano H, Ogawa S (2008) Oncogenic mutations of ALK kinase in neuroblastoma. Nature 455:971–974CrossRefPubMedGoogle Scholar
  11. Chesler L, Weiss WA (2011) Genetically engineered murine models—contribution to our understanding of the genetics, molecular pathology and therapeutic targeting of neuroblastoma. Semin Cancer Biol 21:245–255CrossRefPubMedPubMedCentralGoogle Scholar
  12. Cheung NK, Dyer MA (2013) Neuroblastoma: developmental biology, cancer genomics and immunotherapy. Nat Rev Cancer 13:397–411CrossRefPubMedPubMedCentralGoogle Scholar
  13. Ciccarone V, Spengler BA, Meyers MB, Biedler JL, Ross RA (1989) Phenotypic diversification in human neuroblastoma cells: expression of distinct neural crest lineages. Cancer Res 49:219–225PubMedGoogle Scholar
  14. Corvetta D, Chayka O, Gherardi S, D'Acunto CW, Cantilena S, Valli E, Piotrowska I, Perini G, Sala A (2013) Physical interaction between MYCN oncogene and polycomb repressive complex 2 (PRC2) in neuroblastoma: functional and therapeutic implications. J Biol Chem 288:8332–8341CrossRefPubMedPubMedCentralGoogle Scholar
  15. D'Angio GJ, Evans AE, Koop CE (1971) Special pattern of widespread neuroblastoma with a favourable prognosis. Lancet 1:1046–1049CrossRefPubMedGoogle Scholar
  16. Decock A, Ongenaert M, De Wilde B, Brichard B, Noguera R, Speleman F, Vandesompele J (2016) Stage 4S neuroblastoma tumors show a characteristic DNA methylation portrait. Epigenetics 0Google Scholar
  17. Enomoto H, Crawford PA, Gorodinsky A, Heuckeroth RO, Johnson EM Jr, Milbrandt J (2001) RET signaling is essential for migration, axonal growth and axon guidance of developing sympathetic neurons. Development (Cambridge, England) 128:3963–3974Google Scholar
  18. Espinosa-Medina I, Outin E, Picard CA, Chettouh Z, Dymecki S, Consalez GG, Coppola E, Brunet JF (2014) Neurodevelopment. Parasympathetic ganglia derive from Schwann cell precursors. Science 345:87–90CrossRefPubMedGoogle Scholar
  19. Evans AE, D'Angio GJ, Randolph J (1971) A proposed staging for children with neuroblastoma. Children’s cancer study group A. Cancer 27:374–378CrossRefPubMedGoogle Scholar
  20. Furlan A, Dyachuk V, Kastriti ME, Calvo-Enrique L, Abdo H, Hadjab S, Chontorotzea T, Akkuratova N, Usoskin D, Kamenev D, Petersen J, Sunadome K, Memic F, Marklund U, Fried K, Topilko P, Lallemend F, Kharchenko PV, Ernfors P, Adameyko I (2017) Multipotent peripheral glial cells generate neuroendocrine cells of the adrenal medulla. Science 357Google Scholar
  21. George RE, Sanda T, Hanna M, Frohling S, Luther W 2nd, Zhang J, Ahn Y, Zhou W, London WB, McGrady P, Xue L, Zozulya S, Gregor VE, Webb TR, Gray NS, Gilliland DG, Diller L, Greulich H, Morris SW, Meyerson M, Look AT (2008) Activating mutations in ALK provide a therapeutic target in neuroblastoma. Nature 455:975–978CrossRefPubMedPubMedCentralGoogle Scholar
  22. Gonsalvez DG, Cane KN, Landman KA, Enomoto H, Young HM, Anderson CR (2013) Proliferation and cell cycle dynamics in the developing stellate ganglion. J Neurosci: Off J Soc Neurosci 33:5969–5979CrossRefGoogle Scholar
  23. Guillemot F, Lo LC, Johnson JE, Auerbach A, Anderson DJ, Joyner AL (1993) Mammalian achaete-scute homolog 1 is required for the early development of olfactory and autonomic neurons. Cell 75:463–476CrossRefPubMedGoogle Scholar
  24. Hackett CS, Hodgson JG, Law ME, Fridlyand J, Osoegawa K, de Jong PJ, Nowak NJ, Pinkel D, Albertson DG, Jain A, Jenkins R, Gray JW, Weiss WA (2003) Genome-wide array CGH analysis of murine neuroblastoma reveals distinct genomic aberrations which parallel those in human tumors. Cancer Res 63:5266–5273PubMedGoogle Scholar
  25. Hansford LM, Thomas WD, Keating JM, Burkhart CA, Peaston AE, Norris MD, Haber M, Armati PJ, Weiss WA, Marshall GM (2004) Mechanisms of embryonal tumor initiation: distinct roles for MycN expression and MYCN amplification. Proc Natl Acad Sci U S A 101:12664–12669CrossRefPubMedPubMedCentralGoogle Scholar
  26. Hennchen M, Stubbusch J, Abarchan-El Makhfi I, Kramer M, Deller T, Pierre-Eugene C, Janoueix-Lerosey I, Delattre O, Ernsberger U, Schulte JB, Rohrer H (2015) Lin28B and Let-7 in the control of sympathetic neurogenesis and neuroblastoma development. J Neurosci: Off J Soc Neurosci 35:16531–16544CrossRefGoogle Scholar
  27. Heukamp LC, Thor T, Schramm A, De Preter K, Kumps C, De Wilde B, Odersky A, Peifer M, Lindner S, Spruessel A, Pattyn F, Mestdagh P, Menten B, Kuhfittig-Kulle S, Kunkele A, Konig K, Meder L, Chatterjee S, Ullrich RT, Schulte S, Vandesompele J, Speleman F, Buttner R, Eggert A, Schulte JH (2012) Targeted expression of mutated ALK induces neuroblastoma in transgenic mice. Sci Transl Med 4:141ra191CrossRefGoogle Scholar
  28. Howard MJ, Stanke M, Schneider C, Wu X, Rohrer H (2000) The transcription factor dHAND is a downstream effector of BMPs in sympathetic neuron specification. Development (Cambridge, England) 127:4073–4081Google Scholar
  29. Huber K (2006) The sympathoadrenal cell lineage: specification, diversification, and new perspectives. Dev Biol 298:335–343CrossRefPubMedGoogle Scholar
  30. Huber K (2015) Segregation of neuronal and neuroendocrine differentiation in the sympathoadrenal lineage. Cell Tissue Res 359:333–341CrossRefPubMedGoogle Scholar
  31. Huber K, Bruhl B, Guillemot F, Olson EN, Ernsberger U, Unsicker K (2002) Development of chromaffin cells depends on MASH1 function. Development (Cambridge, England) 129:4729–4738Google Scholar
  32. Janoueix-Lerosey I, Lequin D, Brugieres L, Ribeiro A, de Pontual L, Combaret V, Raynal V, Puisieux A, Schleiermacher G, Pierron G, Valteau-Couanet D, Frebourg T, Michon J, Lyonnet S, Amiel J, Delattre O (2008) Somatic and germline activating mutations of the ALK kinase receptor in neuroblastoma. Nature 455:967–970CrossRefPubMedGoogle Scholar
  33. Kalcheim C, Rohrer H (2014) Neuroscience. Following the same nerve track toward different cell fates. Science 345:32–33CrossRefPubMedGoogle Scholar
  34. Kim YJ, Lim H, Li Z, Oh Y, Kovlyagina I, Choi IY, Dong X, Lee G (2014) Generation of multipotent induced neural crest by direct reprogramming of human postnatal fibroblasts with a single transcription factor. Cell Stem Cell 15:497–506CrossRefPubMedGoogle Scholar
  35. Kim J, Lo L, Dormand E, Anderson DJ (2003) SOX10 maintains multipotency and inhibits neuronal differentiation of neural crest stem cells. Neuron 38:17–31CrossRefPubMedGoogle Scholar
  36. Lumb R, Schwarz Q (2015) Sympathoadrenal neural crest cells: the known, unknown and forgotten? Develop Growth Differ 57:146–157CrossRefGoogle Scholar
  37. Margueron R, Reinberg D (2011) The Polycomb complex PRC2 and its mark in life. Nature 469:343–349CrossRefPubMedPubMedCentralGoogle Scholar
  38. Matthay KK, Maris JM, Schleiermacher G, Nakagawara A, Mackall CL, Diller L, Weiss WA (2016) Neuroblastoma. Nat Rev Dis Prim 2:16078CrossRefPubMedGoogle Scholar
  39. Maurer J, Fuchs S, Jager R, Kurz B, Sommer L, Schorle H (2007) Establishment and controlled differentiation of neural crest stem cell lines using conditional transgenesis. Differ Res Biol Diversity 75:580–591CrossRefGoogle Scholar
  40. Mills AA (2010) Throwing the cancer switch: reciprocal roles of polycomb and trithorax proteins. Nat Rev Cancer 10:669–682CrossRefPubMedPubMedCentralGoogle Scholar
  41. Molenaar JJ, Domingo-Fernandez R, Ebus ME, Lindner S, Koster J, Drabek K, Mestdagh P, van Sluis P, Valentijn LJ, van Nes J, Broekmans M, Haneveld F, Volckmann R, Bray I, Heukamp L, Sprussel A, Thor T, Kieckbusch K, Klein-Hitpass L, Fischer M, Vandesompele J, Schramm A, van Noesel MM, Varesio L, Speleman F, Eggert A, Stallings RL, Caron HN, Versteeg R, Schulte JH (2012) LIN28B induces neuroblastoma and enhances MYCN levels via let-7 suppression. Nat Genet 44:1199–1206CrossRefPubMedGoogle Scholar
  42. Mosse YP, Laudenslager M, Longo L, Cole KA, Wood A, Attiyeh EF, Laquaglia MJ, Sennett R, Lynch JE, Perri P, Laureys G, Speleman F, Kim C, Hou C, Hakonarson H, Torkamani A, Schork NJ, Brodeur GM, Tonini GP, Rappaport E, Devoto M, Maris JM (2008) Identification of ALK as a major familial neuroblastoma predisposition gene. Nature 455:930–935CrossRefPubMedPubMedCentralGoogle Scholar
  43. Nagoshi N, Shibata S, Kubota Y, Nakamura M, Nagai Y, Satoh E, Morikawa S, Okada Y, Mabuchi Y, Katoh H, Okada S, Fukuda K, Suda T, Matsuzaki Y, Toyama Y, Okano H (2008) Ontogeny and multipotency of neural crest-derived stem cells in mouse bone marrow, dorsal root ganglia, and whisker pad. Cell Stem Cell 2:392–403CrossRefPubMedGoogle Scholar
  44. Olsen RR, Otero JH, Garcia-Lopez J, Wallace K, Finkelstein D, Rehg JE, Yin Z, Wang YD, Freeman KW (2017) MYCN induces neuroblastoma in primary neural crest cells. Oncogene 36:5075–5082CrossRefPubMedPubMedCentralGoogle Scholar
  45. Pattyn A, Morin X, Cremer H, Goridis C, Brunet JF (1997) Expression and interactions of the two closely related homeobox genes Phox2a and Phox2b during neurogenesis. Development (Cambridge, England) 124:4065–4075Google Scholar
  46. Pattyn A, Morin X, Cremer H, Goridis C, Brunet JF (1999) The homeobox gene Phox2b is essential for the development of autonomic neural crest derivatives. Nature 399:366–370CrossRefPubMedGoogle Scholar
  47. Peifer M, Hertwig F, Roels F, Dreidax D, Gartlgruber M, Menon R, Kramer A, Roncaioli JL, Sand F, Heuckmann JM, Ikram F, Schmidt R, Ackermann S, Engesser A, Kahlert Y, Vogel W, Altmuller J, Nurnberg P, Thierry-Mieg J, Thierry-Mieg D, Mariappan A, Heynck S, Mariotti E, Henrich KO, Gloeckner C, Bosco G, Leuschner I, Schweiger MR, Savelyeva L, Watkins SC, Shao C, Bell E, Hofer T, Achter V, Lang U, Theissen J, Volland R, Saadati M, Eggert A, de Wilde B, Berthold F, Peng Z, Zhao C, Shi L, Ortmann M, Buttner R, Perner S, Hero B, Schramm A, Schulte JH, Herrmann C, O'Sullivan RJ, Westermann F, Thomas RK, Fischer M (2015) Telomerase activation by genomic rearrangements in high-risk neuroblastoma. Nature 526:700–704CrossRefPubMedPubMedCentralGoogle Scholar
  48. Powers JT, Tsanov KM, Pearson DS, Roels F, Spina CS, Ebright R, Seligson M, de Soysa Y, Cahan P, Theissen J, Tu HC, Han A, Kurek KC, LaPier GS, Osborne JK, Ross SJ, Cesana M, Collins JJ, Berthold F, Daley GQ (2016) Multiple mechanisms disrupt the let-7 microRNA family in neuroblastoma. Nature 535:246–251CrossRefPubMedPubMedCentralGoogle Scholar
  49. Pugh TJ, Morozova O, Attiyeh EF, Asgharzadeh S, Wei JS, Auclair D, Carter SL, Cibulskis K, Hanna M, Kiezun A, Kim J, Lawrence MS, Lichenstein L, McKenna A, Pedamallu CS, Ramos AH, Shefler E, Sivachenko A, Sougnez C, Stewart C, Ally A, Birol I, Chiu R, Corbett RD, Hirst M, Jackman SD, Kamoh B, Khodabakshi AH, Krzywinski M, Lo A, Moore RA, Mungall KL, Qian J, Tam A, Thiessen N, Zhao Y, Cole KA, Diamond M, Diskin SJ, Mosse YP, Wood AC, Ji L, Sposto R, Badgett T, London WB, Moyer Y, Gastier-Foster JM, Smith MA, Guidry Auvil JM, Gerhard DS, Hogarty MD, Jones SJ, Lander ES, Gabriel SB, Getz G, Seeger RC, Khan J, Marra MA, Meyerson M, Maris JM (2013) The genetic landscape of high-risk neuroblastoma. Nat Genet 45:279–284CrossRefPubMedPubMedCentralGoogle Scholar
  50. Saito D, Takahashi Y (2015) Sympatho-adrenal morphogenesis regulated by the dorsal aorta. Mech Dev 138(Pt 1):2–7CrossRefPubMedGoogle Scholar
  51. Saito D, Takase Y, Murai H, Takahashi Y (2012) The dorsal aorta initiates a molecular cascade that instructs sympatho-adrenal specification. Science 336:1578–1581CrossRefPubMedGoogle Scholar
  52. Sauka-Spengler T, Bronner-Fraser M (2008) A gene regulatory network orchestrates neural crest formation. Nat Rev Mol Cell Biol 9:557–568CrossRefPubMedGoogle Scholar
  53. Schneider C, Wicht H, Enderich J, Wegner M, Rohrer H (1999) Bone morphogenetic proteins are required in vivo for the generation of sympathetic neurons. Neuron 24:861–870CrossRefPubMedGoogle Scholar
  54. Schulte JH, Lindner S, Bohrer A, Maurer J, De Preter K, Lefever S, Heukamp L, Schulte S, Molenaar J, Versteeg R, Thor T, Kunkele A, Vandesompele J, Speleman F, Schorle H, Eggert A, Schramm A (2013) MYCN and ALKF1174L are sufficient to drive neuroblastoma development from neural crest progenitor cells. Oncogene 32:1059–1065CrossRefPubMedGoogle Scholar
  55. Suenaga Y, Islam SM, Alagu J, Kaneko Y, Kato M, Tanaka Y, Kawana H, Hossain S, Matsumoto D, Yamamoto M, Shoji W, Itami M, Shibata T, Nakamura Y, Ohira M, Haraguchi S, Takatori A, Nakagawara A (2014) NCYM, a Cis-antisense gene of MYCN, encodes a de novo evolved protein that inhibits GSK3beta resulting in the stabilization of MYCN in human neuroblastomas. PLoS Genet 10:e1003996CrossRefPubMedPubMedCentralGoogle Scholar
  56. Takahashi Y, Sipp D, Enomoto H (2013) Tissue interactions in neural crest cell development and disease. Science 341:860–863CrossRefPubMedGoogle Scholar
  57. Tolbert VP, Coggins GE, Maris JM (2017) Genetic susceptibility to neuroblastoma. Curr Opin Genet Dev 42:81–90CrossRefPubMedGoogle Scholar
  58. Tsarovina K, Pattyn A, Stubbusch J, Muller F, van der Wees J, Schneider C, Brunet JF, Rohrer H (2004) Essential role of Gata transcription factors in sympathetic neuron development. Development (Cambridge, England) 131:4775–4786CrossRefGoogle Scholar
  59. Tsubota S, Kishida S, Shimamura T, Ohira M, Yamashita S, Cao D, Kiyonari S, Ushijima T, Kadomatsu K (2017) PRC2-mediated transcriptomic alterations at the embryonic stage govern tumorigenesis and clinical outcome in MYCN-driven neuroblastoma. Cancer researchGoogle Scholar
  60. Valentijn LJ, Koster J, Zwijnenburg DA, Hasselt NE, van Sluis P, Volckmann R, van Noesel MM, George RE, Tytgat GA, Molenaar JJ, Versteeg R (2015) TERT rearrangements are frequent in neuroblastoma and identify aggressive tumors. Nat Genet 47:1411–1414CrossRefPubMedGoogle Scholar
  61. van Groningen T, Koster J, Valentijn LJ, Zwijnenburg DA, Akogul N, Hasselt NE, Broekmans M, Haneveld F, Nowakowska NE, Bras J, van Noesel CJM, Jongejan A, van Kampen AH, Koster L, Baas F, van Dijk-Kerkhoven L, Huizer-Smit M, Lecca MC, Chan A, Lakeman A, Molenaar P, Volckmann R, Westerhout EM, Hamdi M, van Sluis PG, Ebus ME, Molenaar JJ, Tytgat GA, Westerman BA, van Nes J, Versteeg R (2017) Neuroblastoma is composed of two super-enhancer-associated differentiation states. Nat Genet 49:1261–1266CrossRefPubMedGoogle Scholar
  62. van Noesel MM (2012) Neuroblastoma stage 4S: a multifocal stem-cell disease of the developing neural crest. Lancet Oncol 13:229–230CrossRefPubMedGoogle Scholar
  63. Viswanathan SR, Daley GQ, Gregory RI (2008) Selective blockade of microRNA processing by Lin28. Science 320:97–100CrossRefPubMedPubMedCentralGoogle Scholar
  64. Vo KT, Matthay KK, Neuhaus J, London WB, Hero B, Ambros PF, Nakagawara A, Miniati D, Wheeler K, Pearson AD, Cohn SL, DuBois SG (2014) Clinical, biologic, and prognostic differences on the basis of primary tumor site in neuroblastoma: a report from the international neuroblastoma risk group project. J Clin Oncol 32:3169–3176CrossRefPubMedPubMedCentralGoogle Scholar
  65. Wang C, Liu Z, Woo CW, Li Z, Wang L, Wei JS, Marquez VE, Bates SE, Jin Q, Khan J, Ge K, Thiele CJ (2012) EZH2 mediates epigenetic silencing of neuroblastoma suppressor genes CASZ1, CLU, RUNX3, and NGFR. Cancer Res 72:315–324CrossRefPubMedGoogle Scholar
  66. Weiss WA, Aldape K, Mohapatra G, Feuerstein BG, Bishop JM (1997) Targeted expression of MYCN causes neuroblastoma in transgenic mice. EMBO J 16:2985–2995CrossRefPubMedPubMedCentralGoogle Scholar
  67. Wong CE, Paratore C, Dours-Zimmermann MT, Rochat A, Pietri T, Suter U, Zimmermann DR, Dufour S, Thiery JP, Meijer D, Beermann F, Barrandon Y, Sommer L (2006) Neural crest-derived cells with stem cell features can be traced back to multiple lineages in the adult skin. J Cell Biol 175:1005–1015CrossRefPubMedPubMedCentralGoogle Scholar
  68. Zhu S, Lee JS, Guo F, Shin J, Perez-Atayde AR, Kutok JL, Rodig SJ, Neuberg DS, Helman D, Feng H, Stewart RA, Wang W, George RE, Kanki JP, Look AT (2012) Activated ALK collaborates with MYCN in neuroblastoma pathogenesis. Cancer Cell 21:362–373CrossRefPubMedPubMedCentralGoogle Scholar

Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2018

Authors and Affiliations

  1. 1.Department of BiochemistryNagoya University Graduate School of MedicineNagoyaJapan

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