Skip to main content
SpringerLink
Log in

Origin and initiation mechanisms of neuroblastoma

  • Review
  • Published:
Cell and Tissue Research Aims and scope Submit manuscript

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.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3

Similar content being viewed by others

References

  • 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 50:628–637

    Article  CAS  PubMed  Google Scholar 

  • 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 2:261–271

    Article  PubMed  PubMed Central  Google Scholar 

  • 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 40:499–507

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • 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 22:117–130

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • 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 49:1408–1413

    Article  CAS  PubMed  Google Scholar 

  • 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:e0185190

    Article  PubMed  PubMed Central  Google Scholar 

  • Brodeur GM, Bagatell R (2014) Mechanisms of neuroblastoma regression. Nat Rev Clin Oncol 11:704–713

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • 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 56:1428–1437

    Article  PubMed  Google Scholar 

  • 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 5:2688–2702

    Article  PubMed  PubMed Central  Google Scholar 

  • 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 455:971–974

    Article  CAS  PubMed  Google Scholar 

  • 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 21:245–255

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Cheung NK, Dyer MA (2013) Neuroblastoma: developmental biology, cancer genomics and immunotherapy. Nat Rev Cancer 13:397–411

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • 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 49:219–225

    CAS  PubMed  Google Scholar 

  • 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 288:8332–8341

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • D'Angio GJ, Evans AE, Koop CE (1971) Special pattern of widespread neuroblastoma with a favourable prognosis. Lancet 1:1046–1049

    Article  PubMed  Google Scholar 

  • 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 0

  • 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) 128:3963–3974

    CAS  Google Scholar 

  • 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 345:87–90

    Article  CAS  PubMed  Google Scholar 

  • Evans AE, D'Angio GJ, Randolph J (1971) A proposed staging for children with neuroblastoma. Children’s cancer study group A. Cancer 27:374–378

    Article  CAS  PubMed  Google Scholar 

  • 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 357

  • 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 455:975–978

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • 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 33:5969–5979

    Article  CAS  Google Scholar 

  • 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 75:463–476

    Article  CAS  PubMed  Google Scholar 

  • 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 63:5266–5273

    CAS  PubMed  Google Scholar 

  • 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 101:12664–12669

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • 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 35:16531–16544

    Article  CAS  Google Scholar 

  • 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 4:141ra191

    Article  Google Scholar 

  • 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) 127:4073–4081

  • Huber K (2006) The sympathoadrenal cell lineage: specification, diversification, and new perspectives. Dev Biol 298:335–343

    Article  CAS  PubMed  Google Scholar 

  • Huber K (2015) Segregation of neuronal and neuroendocrine differentiation in the sympathoadrenal lineage. Cell Tissue Res 359:333–341

    Article  CAS  PubMed  Google Scholar 

  • Huber K, Bruhl B, Guillemot F, Olson EN, Ernsberger U, Unsicker K (2002) Development of chromaffin cells depends on MASH1 function. Development (Cambridge, England) 129:4729–4738

  • 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 455:967–970

    Article  CAS  PubMed  Google Scholar 

  • Kalcheim C, Rohrer H (2014) Neuroscience. Following the same nerve track toward different cell fates. Science 345:32–33

    Article  CAS  PubMed  Google Scholar 

  • 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 15:497–506

    Article  CAS  PubMed  Google Scholar 

  • Kim J, Lo L, Dormand E, Anderson DJ (2003) SOX10 maintains multipotency and inhibits neuronal differentiation of neural crest stem cells. Neuron 38:17–31

    Article  CAS  PubMed  Google Scholar 

  • Lumb R, Schwarz Q (2015) Sympathoadrenal neural crest cells: the known, unknown and forgotten? Develop Growth Differ 57:146–157

    Article  Google Scholar 

  • Margueron R, Reinberg D (2011) The Polycomb complex PRC2 and its mark in life. Nature 469:343–349

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Matthay KK, Maris JM, Schleiermacher G, Nakagawara A, Mackall CL, Diller L, Weiss WA (2016) Neuroblastoma. Nat Rev Dis Prim 2:16078

    Article  PubMed  Google Scholar 

  • 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 75:580–591

    Article  CAS  Google Scholar 

  • Mills AA (2010) Throwing the cancer switch: reciprocal roles of polycomb and trithorax proteins. Nat Rev Cancer 10:669–682

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • 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 44:1199–1206

    Article  CAS  PubMed  Google Scholar 

  • 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 455:930–935

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • 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 2:392–403

    Article  CAS  PubMed  Google Scholar 

  • 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 36:5075–5082

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • 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) 124:4065–4075

    CAS  Google Scholar 

  • 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 399:366–370

    Article  CAS  PubMed  Google Scholar 

  • 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 526:700–704

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • 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 535:246–251

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • 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 45:279–284

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Saito D, Takahashi Y (2015) Sympatho-adrenal morphogenesis regulated by the dorsal aorta. Mech Dev 138(Pt 1):2–7

    Article  CAS  PubMed  Google Scholar 

  • Saito D, Takase Y, Murai H, Takahashi Y (2012) The dorsal aorta initiates a molecular cascade that instructs sympatho-adrenal specification. Science 336:1578–1581

    Article  CAS  PubMed  Google Scholar 

  • Sauka-Spengler T, Bronner-Fraser M (2008) A gene regulatory network orchestrates neural crest formation. Nat Rev Mol Cell Biol 9:557–568

    Article  CAS  PubMed  Google Scholar 

  • 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 24:861–870

    Article  CAS  PubMed  Google Scholar 

  • 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 32:1059–1065

    Article  CAS  PubMed  Google Scholar 

  • 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:e1003996

    Article  PubMed  PubMed Central  Google Scholar 

  • Takahashi Y, Sipp D, Enomoto H (2013) Tissue interactions in neural crest cell development and disease. Science 341:860–863

    Article  CAS  PubMed  Google Scholar 

  • Tolbert VP, Coggins GE, Maris JM (2017) Genetic susceptibility to neuroblastoma. Curr Opin Genet Dev 42:81–90

    Article  CAS  PubMed  Google Scholar 

  • 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) 131:4775–4786

    Article  CAS  Google Scholar 

  • 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 research

  • 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 47:1411–1414

    Article  CAS  PubMed  Google Scholar 

  • 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 49:1261–1266

    Article  PubMed  Google Scholar 

  • van Noesel MM (2012) Neuroblastoma stage 4S: a multifocal stem-cell disease of the developing neural crest. Lancet Oncol 13:229–230

    Article  PubMed  Google Scholar 

  • Viswanathan SR, Daley GQ, Gregory RI (2008) Selective blockade of microRNA processing by Lin28. Science 320:97–100

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • 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 32:3169–3176

    Article  PubMed  PubMed Central  Google Scholar 

  • 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 72:315–324

    Article  CAS  PubMed  Google Scholar 

  • Weiss WA, Aldape K, Mohapatra G, Feuerstein BG, Bishop JM (1997) Targeted expression of MYCN causes neuroblastoma in transgenic mice. EMBO J 16:2985–2995

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • 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 175:1005–1015

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • 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 21:362–373

    Article  CAS  PubMed  PubMed Central  Google Scholar 

Download references

Funding

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).

Author information

Authors and Affiliations

  1. Department of Biochemistry, Nagoya University Graduate School of Medicine, 65 Tsurumai-Cho, Showa-Ku, Nagoya, 466-8550, Japan

    Shoma Tsubota & Kenji Kadomatsu

Authors
  1. Shoma Tsubota
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Kenji Kadomatsu
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Kenji Kadomatsu.

Ethics declarations

Conflict of interest

The authors declare that they have no conflicts of interest.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Tsubota, S., Kadomatsu, K. Origin and initiation mechanisms of neuroblastoma. Cell Tissue Res 372, 211–221 (2018). https://doi.org/10.1007/s00441-018-2796-z

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00441-018-2796-z

Keywords

Search

Navigation