Skip to main content
SpringerLink
Log in

Neuroblastoma and Neuroblastic Tumors

  • Chapter
  • First Online:
Precision Molecular Pathology of Neoplastic Pediatric Diseases

Part of the book series: Molecular Pathology Library ((MPLB))

  • 555 Accesses

Abstract

Peripheral neuroblastic tumors (pNTs) including neuroblastoma, ganglioneuroblastoma, and ganglioneuroma are composed of biologically favorable and biologically unfavorable group. Tumors in the former group can show spontaneous regression or tumor maturation. In contrast, those in the latter group are often aggressive and refractory to treatment. Molecular/genomic characteristics of these biologically different groups and their prognostic impacts are described in this chapter. After discussing the risk-grouping system for pNT patients, recent progress of molecular pathology in precision medicine especially for children with high-risk neuroblastomas is summarized. The progress of pathology research in this disease also includes an establishment of a new concept, MYC family-driven neuroblastoma (including large-cell neuroblastoma) defined by augmented expression of MYCN and/or MYC protein of neuroblastic cells.

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

Access this chapter

Log in via an institution
Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 79.99
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 99.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 129.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

References

  1. Shimada H, Ambros I, Dehner PL, Hata J, Joshi VV, Roald B. Terminology and morphologic criteria of neuroblastic tumors: recommendation by the International Neuroblastoma Pathology Committee. Cancer. 1999;86:349–63.

    Article  CAS  PubMed  Google Scholar 

  2. Howlader N, Noone A, Krapcho M, Garshell J, Miller D, Altekruse SF, Kosary CL, Yu M, Ruhl J, Tatalovich Z, Mariotto A, Lewis DR, Chen HS, Feuer EJ, Cronin KA, editors. SEER cancer statistics review, 1975–2012. Bethesda: National Cancer Institute; 2015. http://seer.cancer.gov/csr/1975_2012/

    Google Scholar 

  3. Brodeur GM, Hogarty MD, Moose YP, Maris JM. Neuroblastoma. In: Pizzo PA, Poplack DG, editors. Principles and practice of pediatric oncology. Philadelphia: Lippincott Williams & Wilkins; 2011. p. 886–922. Book, ISBN: 978-1-60547-682-7.

    Google Scholar 

  4. Pajtler KW, Mahlow E, Odersky A, Lindner S, Stephan H, Eggert A, Schramm A, Schulte JH. Neuroblastoma in dialog with its stroma: NTRK1 is a regulator of cellular cross-talk with Schwann cells. Oncotarget. 2014;5:11180–92.

    Article  PubMed  PubMed Central  Google Scholar 

  5. Brodeur GM, Nakagawara A, Yamashiro DJ, Ikegaki N, Liu XG, Azar CG, Lee CP, Evans AE. Expression of TrkA, TrkB and TrkC in human neuroblastomas. J Neuro-Oncol. 1997;31:49–55.

    Article  CAS  Google Scholar 

  6. Nakagawara A, Azar CG, Scavarda NJ, Brodeur GM. Expression and function of Trk-B and BDNF in human neuroblastomas. Mol Cell Biol. 1994;14:759–67.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  7. Look AT, Hayes FA, Nitschke R, McWilliams NB, Green AA. Cellular DNA content as a predictor of response to chemotherapy in infants with unresectable neuroblastoma. N Engl J Med. 1984;311:231–5.

    Article  CAS  PubMed  Google Scholar 

  8. George RE, London WB, Cohn SL, Maris JM, Kretschmar C, Diller L, Brodeur GM, Castleberry RP, Look AT. Hyperdiploid plus nonamplified MYCN confers a favorable prognosis in children 12 to 18 months old with disseminated neuroblastoma: a Pediatric Oncology Group study. J Clin Oncol. 2005;23:6466–73.

    Article  CAS  PubMed  Google Scholar 

  9. Brodeur GM, Seeger RC, Schwab M, Varmus HE, Bishop JM. Amplification of N-myc in untreated human neuroblastomas correlates with advanced disease stage. Science. 1984;224:1121–4.

    Article  CAS  PubMed  Google Scholar 

  10. Seeger RC, Brodeur GM, Sather H, Dalton A, Siegel SE, Wong KY, Hammond D. Association of multiple copies of the N-myc oncogene with rapid progression of neuroblastomas. N Engl J Med. 1985;313:1111–6.

    Article  CAS  PubMed  Google Scholar 

  11. Ambros PF, Ambros IM, Brodeur GM, Haber M, Khan J, Nakagawara A, Schleiermacher G, Speleman F, Spitz R, London WB, Cohn SL, Pearson ADJ, Maris JM. International consensus for neuroblastoma molecular diagnostics: report from the International Neuroblastoma Risk Group (INRG) Biology Committee. Br J Cancer. 2009;100:1471–82.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  12. Molenaar JJ, Domingo-Fernández 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, Sprüssel 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. LIN28B induces neuroblastoma and enhances MYCN levels via let-7 suppression. Nat Genet. 2012;44:1199–206.

    Article  CAS  PubMed  Google Scholar 

  13. Beckers A, van Peer G, Carter DR, Gartlgruber M, Herrmann C, Agarwal S, Helsmoortel HH, Althoff K, Molenaar JJ, Cheung BB, Schulte JH, Benoit Y, Shohet JM, Westermann F, Marshall GM, Vandesompele J, Preter KD, Speleman F. MYCN-driven regulatory mechanisms controlling LIN28B in neuroblastoma. Cancer Lett. 2015;366:123–32.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  14. Schleiermacher G, Delattre O, Peter M, Mosseri V, delonlay P, Vielh P, Thomas G, Zucker JM, Magdelenat H, Michon J. Clinical relevance of loss heterozygosity of the short arm of chromosome 1 in neuroblastoma: a single institution study. Int J Cancer. 1996;69:73–8.

    Article  CAS  PubMed  Google Scholar 

  15. Spitz R, Hero B, Ernestus K, Berthold F. Deletions in chromosome arms 3p and 11q are new prognostic markers in localized and 4s neuroblastoma. Clin Cancer Res. 2003;9:52–85.

    PubMed  CAS  Google Scholar 

  16. Attiyeh EF, London WB, Mosse YP, Wang Q, Winter C, Khazi D, McGrady PW, Seeger RC, Look AT, Shimada H, Brodeur GM, Cohn SL, Matthay KK, Maris JM. Chromosome 1p and 11q deletions and outcome in neuroblastoma. N Engl J Med. 2005;353:2243–53.

    Article  CAS  PubMed  Google Scholar 

  17. Caren H, Kryh H, Nethander M, Sjoberg RM, Trager C, Nilsson S, Abrahamsson J, Kogner P, Martinsson T. High-risk neuroblastoma tumors with 11q-deletion display a poor prognostic, chromosome instability phenotype with later onset. Proc Natl Acad Sci U S A. 2010;107:4323–8.

    Article  PubMed  PubMed Central  Google Scholar 

  18. Maris JM. Recent advances in neuroblastoma. N Engl J Med. 2010;362:2202–11.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  19. Bown N, Cotterill S, Lastowska M, O’Neill S, Pearson AD, Plantaz D, Meddeb M, Danglot G, Brinkschmidt C, Christiansen H, Laureys G, Speleman F, Nicholson J, Bernheim A, Betts DR, Vandesompele J, Van Roy N. Gain of chromosome arm 17q and adverse outcome in patients with neuroblastoma. N Engl J Med. 1999;340:1954–61.

    Article  CAS  PubMed  Google Scholar 

  20. Pezzolo A, Rossi E, Gimelli S, Parodi F, Negri F, Conte M, Pistorio A, Sementa A, Pistoia V, Zuffardi O, Gambini C. Presence of 1q gain and absence of 7p gain are new predictors of local or metastatic relapse in localized resettable neuroblastoma. Neuro-Oncology. 2009;11:192–200.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  21. Schleiermacher G, Nosseri V, London WB, Maris JM, Brodeur GM, Attiyeh E, Haber M, Khan J, Nakagawara A, Speleman F, Noguera R, Tonini GP, Fischer M, Ambros I, Monclair T, Matthay KK, Ambros P, Cohn SL, Pearson ADJ. Segmental chromosomal alterations have prognostic impact in neuroblastoma: a report from the INRG project. Br J Cancer. 2012;107:1418–22.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  22. 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. Identification of ALK as a major familial neuroblastoma predisposition gene. Nature. 2008;455:930–5.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  23. Janoueix-Lerosey I, Lequin D, Grugieres L, Ribeiro A, de Pontual L, Combaret V, Raynal V, Schleiermacher G, Pierron G, Valteau-Couanet D, Freboung T, Michon J, Lyonnet S, Amiel J, Delattre O. Somatic and germline activating mutations of the ALK kinase receptor in neuroblastoma. Nature. 2008;455:967–70.

    Article  CAS  PubMed  Google Scholar 

  24. 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. Oncogenic mutations of ALK kinase in neuroblastoma. Nature. 2008;455:971–4.

    Article  CAS  PubMed  Google Scholar 

  25. George RE, Sanda T, Hanna M, Froehling S, Luther W, 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. Activating mutations in ALK provide a therapeutic target in neuroblastoma. Nature. 2008;455:975–8.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  26. Mosse YP. Anaplastic lymphoma kinase as a cancer target in pediatric malignancies. Clin Cancer Res. 2016;22:546–52.

    Article  CAS  PubMed  Google Scholar 

  27. Sausen M, Leary RJ, Jones S, Wu J, Reynolds CP, Liu X, Blackford A, Parmigiani G, Diaz LA Jr, Papadopoulos N, Vogelstein B, Kinzler KW, Velculescu VW, Hogarty MD. Integrated genomic analyses identify ARID 1A and ARID 1B alterations in the childhood cancer neuroblastoma. Nat Genet. 2012;45:12–7.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  28. Peifer M, Hertwig F, Roels F, Dreidax D, Gartlgruber M, Menon R, Kraemer A, Roncaioli JL, Sand F, Heuckmann JM, Ikram F, Schmidt R, Ackermann S, Engesser A, Kahlert Y, Vogel W, Altmueller J, Nuernberg P, Thierry-Mieg J, Thierry-Mieg D, Marippan A, Heynck S, Mariotti E, Henrich KO, Gloechner C, Bosco G, Leuschner I, Schweiger MR, Savelyeva L, Watkins SC, Shao C, Bell E, Hoefer T, Archter V, Laug U, Theussen J, Volland R, Saadati M, Eggert A, de Wilde B, Berthold F, Peng Z, Zhao C, Shi L, Ortmann M, Buettner R, Perner S, Hero B, Schramm A, Schulte JH, Herrmann C, O’Sullivan RJ, Westermann F, Thomas RK, Fischer M. Telomerase activation by genomic rearrangements in high-risk neuroblastoma. Nature. 2015;526:700–4.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  29. Valentijn LJ, Koster J, Zwijnenburg DA, Hasselt NE, van Sluis P, Volckmann R, van Noesel MM, George RE, Tytgat GA, Molenaar JJ, Versteeg R. TERT rearrangements are frequent in neuroblastoma and identify aggressive tumors. Nat Genet. 2015;47:1411–4.

    Article  CAS  PubMed  Google Scholar 

  30. Cheung NK, Zhang J, Lu C, Parker M, Bahrami A, Tickoo SK, Heguy A, Pappo AS, Federico S, Dalton J, Cheung IY, Ding L, Fulton R, Wang J, Chen X, Becksfort J, Wu J, Billups CA, Ellison RK, Mardis ER, Wilson RK, Downing JR, Dyer MA, St. Jude Children’s Research Hospital-Washington University Pediatric Cancer Genome Project. Association of age at diagnosis and genetic mutations in patients with neuroblastoma. JAMA. 2012;307:1062–71.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  31. Kurihara S, Hiyama E, Onitake Y, Yamaoka E, Hiyama K. Clinical features of ATRX or DAXX mutated neuroblastoma. J Pediatr Surg. 2014;49:1835–8.

    Article  PubMed  Google Scholar 

  32. Molenaar JJ, Koster J, Zwijnenburg DA, van Sluis P, Valentijn LJ, van der Ploeg I, Hamdi M, van Nes J, Westerman BA, van Arkel J, Ebus ME, Haneveld F, Lakeman A, Schild L, Molenaar P, Stroeken P, van Noesel MM, Ora I, Santo EE, Canon HN, Westerhout EM, Versteeg R. Sequencing of neuroblastoma identifies chromothripsis and defects in neuritogenesis genes. Nature. 2012;483:589–93.

    Article  CAS  PubMed  Google Scholar 

  33. Pugh TJ, Morozova O, Attiyeh EF, Asgharzadeh S, Wei SJ, 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 TP, 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. The genetic landscape of high-risk neuroblastoma. Nat Genet. 2013;45:279–84.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  34. Maris JM, Mosse YP, Bradfield JP, Hou C, Monni S, Scott RH, Asgharzadeh S, Attiyeh EF, Diskin SJ, Laudenslager M, Winter C, Cole KA, Glessner JT, Kim C, Frackelton EC, Casalunovo T, Eckert AW, Capasso T, Rappaport EF, McConville C, London WB, Seeger RC, Rahman N, Devoto M, Grant SF, Li H, Hakonarson H. Chromosome 6p22 locus associated with clinically aggressive neuroblastoma. N Engl J Med. 2008;358:2585–93.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  35. Bosse KR, Diskin SJ, Cole KA, Wood AC, Schnepp RW, Norris G, Nguyen le B, Jagannathan J, Laquaglia M, Winter C, Diamond M, Hou C, Attiyeh EF, Moose YP, Pineros V, Dizin E, Zhang Y, Asgharzadeh S, Seeger RC, Capasso M, Pawel BR, Devoto M, Hakonarson H, Rappaport EF, Irminger-Finger I, Maris JM. Common variation at BARD1 results in the expression of an oncogenic isoform that influences neuroblastoma susceptibility and oncogenicity. Cancer Res. 2012;72:2068–78.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  36. Wang K, Diskin SJ, Zhang H, Attiyeh EF, Winter C, Hou C, Schnepp RW, Diamond M, Bosse K, Mayes PA, Glessner J, Kim C, Frackelton E, Garris M, Wang Q, Glaberson W, Chiavacci R, Nguyen L, Jagannathan J, Saeki N, Sasaki H, Grant SF, Iolascon A, Mosse YP, Cole KA, Li H, Devoto M, McGrady PW, London WB, Capasso M, Rahman N, Hakonarson H, Maris JM. Integrative genomics identifies LMO1 as a neuroblastoma oncogene. Nature. 2011;469:216–20.

    Article  CAS  PubMed  Google Scholar 

  37. Nguyen le B, Diskin SJ, Capasso M, Wang K, Diamond MA, Glessner MA, Kim C, Attiyeh EF, Mosse YP, Cole K, Iolascon A, Devoto M, Hakonarson H, Li HK, Maris JM. Phenotype restricted genome-wide association study using a gene-centric approach identifies three low-risk neuroblastoma susceptibility loci. PLoS Genet. 2011;7:e1002026.

    Article  CAS  PubMed  Google Scholar 

  38. Diskin SJ, Cappaso M, Schnepp RW, Cole KA, Attiyeh EF, Hou C, Diamond M, Carpenter EL, Winter C, Lee H, Jagannathan J, Latorre V, Iolascon A, Hakonarson H, Devoto M, Maris JM. Common variation at 6q16 within HACE1 and LIN28B influences susceptibility to neuroblastoma. Nat Genet. 2012;44:1126–30.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  39. Capasso M, Diskin SJ, Totaro F, Longo L, de Mariano M, Russo R, Cimmio F, Hakonarson H, Tonini GP, Devoto M, Maris JM, Iolascon A. Replication of GWAS-identified neuroblastoma risk loci strengthenes the role of BARD1 and affirms the cumulative effort of genetic variations on disease susceptibility. Carcinogenesis. 2013;34:605–11.

    Article  CAS  PubMed  Google Scholar 

  40. London WB, Castleberry RP, Matthay KK, Look AT, Seeger RC, Shimada H, Thorner P, Brodeur G, Maris JM, Reynolds CP, Cohn SL. Evidence for an age cutoff greater than 365 days for neuroblastoma risk group stratification in the Children’s Oncology Group. J Clin Oncol. 2005;23:6459–65.

    Article  CAS  PubMed  Google Scholar 

  41. Shimada H, Ambros IM, Dehner LP, Hata J, Joshi VV, Roald B, Stram DO, Gerbing RB, Lukens JN, Matthay KK, Castleberry RP. The International Neuroblastoma Pathology Classification (the Shimada system). Cancer. 1999;86:364–72.

    Article  CAS  PubMed  Google Scholar 

  42. Park JR, Bagatell R, London WB, Maris JM, Cohn SL, Matthay KK, Hogarty MD. Children’s Oncology Group’s 2013 blueprint for research: neuroblastoma. Pediatr Blood Cancer. 2013;60:985–93.

    Article  PubMed  Google Scholar 

  43. Cohn SL, Pearson AD, London WB, Monclair T, Ambros PF, Brodeur GM, Faldum A, Hero B, Iehara T, Machin D, Mosseri V, Simon T, Garaventa A, Castel V, Matthay KK, INRG Task Force. The International Neuroblastoma Risk Group (INRG) classification system: an INRG Task Force report. J Clin Oncol. 2009;27:289–97.

    Article  PubMed  PubMed Central  Google Scholar 

  44. Monclair T, Brodeur GM, Ambros PF, Bfisse HJ, Cecchetto G, Holmes K, Kaneko M, London WB, Matthay KK, Nuchtern JG, von Schweinitz D, Simon T, Cohn SL, Pearson AD, INRG Rask Force. The International Neuroblastoma Risk Group (INRG) staging system: an INRG Task Force report. J Clin Oncol. 2009;27:298–303.

    Article  PubMed  PubMed Central  Google Scholar 

  45. Robert C, Karaszewska B, Schachter J, Rutkowski P, Mackiewicz A, Stroiakovski D, Lichinitser M, Dummer R, Grange F, Mortier L, Chiarion-Sileni V, Drucis K, Krajsova I, Hauschild A, Lorigan P, Wolter P, Long GV, Flaherty K, Nathan P, Ribas A, Martin AM, Sun P, Crist W, Legos J, Rubin SD, Little SM, Schadendorf D. Improved overall survival in melanoma with combined dabrafenib and trametinib. N Engl J Med. 2015;372:30–9.

    Article  CAS  PubMed  Google Scholar 

  46. Regairaz M, Munier F, Sartelet H, Castaing M, Marty V, Renauleaud C, Doux C, Delbé J, Courty J, Fabre M, Ohta S, Viehl P, Michiels S, Valteau-Couanet D, Vassal G. Mutation-independent activation of the anaplastic lymphoma kinase in neuroblastoma. Am J Pathol. 2016;186:435–45.

    Article  CAS  PubMed  Google Scholar 

  47. Saulnier Sholler GL, Bond JP, Bergendahl G, Dutta A, Dragon J, Neville K, Ferguson W, Roberts W, Eslin D, Kraveka J, Kaplan J, Mitchell D, Parikh N, Merchant M, Ashikaga T, Hanna G, Lescault PJ, Siniard A, Corneveaux J, Huentelman M, Trent J. Feasibility of implementing molecular-guided therapy for the treatment of patients with relapsed or refractory neuroblastoma. Cancer Med. 2015;4:871–86.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  48. Costello JC, Heiser LM, Georgii E, Gönen M, Menden MP, Wang NJ, Bansal M, Ammad-ud-din M, Hintsanen P, Khan SA, Mpindi JP, Kallioniemi O, Honkela A, Aittokallio T, Wennerberg K, NCI DREAM Community, Collins JJ, Gallahan D, Singer D, Saez-Rodriguez J, Kaski S, Gray JW, Stolovitzky G. A community effort to assess and improve drug sensitivity prediction algorithms. Nat Biotechnol. 2014;32:1202–12.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  49. Braekeveldt N, Wigerup C, Gisselsson D, Mohlin S, Merselius M, Beckman S, Jonson T, Börjesson A, Backman T, Tadeo I, Berbegall AP, Ora I, Navarro S, Noguera R, Påhlman S, Bexell D. Neuroblastoma patient-derived orthotopic xenografts retain metastatic patterns and geno- and phenotypes of patient tumours. Int J Cancer. 2015;136:E252–61.

    Article  CAS  PubMed  Google Scholar 

  50. Braekeveldt N, Wigerup C, Tadeo I, Beckman S, Sandén C, Jönsson J, Erjefält JS, Berbegall AP, Börjesson A, Backman T, Øra I, Navarro S, Noguera R, Gisselsson D, Påhlman S, Bexell D. Neuroblastoma patient-derived orthotopic xenografts reflect the microenvironmental hallmarks of aggressive patient tumours. Cancer Lett. 2016;375:384–9.

    Article  CAS  PubMed  Google Scholar 

  51. Krytska K, Ryles HT, Sano R, Raman P, Infarinato NR, Hansel TD, Makena MR, Song MM, Reynolds CP, Mossé YP. Crizotinib synergizes with chemotherapy in preclinical models of neuroblastoma. Clin Cancer Res. 2016;22:948–60.

    Article  CAS  PubMed  Google Scholar 

  52. Rodríguez-Hernández CJ, Mateo-Lozano S, García M, Casalà C, Briansó F, Castrejón N, Rodríguez E, Suñol M, Carcaboso AM, Lavarino C, Mora J, de Torres C. Cinacalcet inhibits neuroblastoma tumor growth and upregulates cancer-testis antigens. Oncotarget. 2016;7:16112–29.

    Article  PubMed  PubMed Central  Google Scholar 

  53. Ikegaki N, Shimada H, Fox AM, Regan PL, Jacobs JR, Hicks SL, Rappaport EF, Tang XX. Transient treatment with epigenetic modifiers yields stable neuroblastoma stem cells resembling aggressive large-cell neuroblastomas. Proc Natl Acad Sci U S A. 2013;110:6097–102.

    Article  PubMed  PubMed Central  Google Scholar 

  54. Tornóczky T, Kálmán E, Kajtár PG, Nyári T, Pearson AD, Tweddle DA, Board J, Shimada H. Large cell neuroblastoma: a distinct phenotype of neuroblastoma with aggressive clinical behavior. Cancer. 2004;100:390–7.

    Article  PubMed  Google Scholar 

  55. Davidoff AM. Neuroblastoma. Semin Pediatr Surg. 2012;21:2–14.

    Article  PubMed  PubMed Central  Google Scholar 

  56. Pinto NR, Applebaum MA, Volchenboum SL, Matthay KK, London WB, Ambros PF, Nakagawara A, Berthold F, Schleiermacher G, Park JR, Valteau-Couanet D, Pearson AD, Cohn SL. Advances in risk classification and treatment strategies for neuroblastoma. J Clin Oncol. 2015;33:3008–17.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  57. Saarinen-Pihkala UM, Jahnukainen K, Wikström S, Koivusalo A, Karikoski R, Sariola H, Hovi L. Ultrahigh-risk group within the high-risk neuroblastoma category. J Pediatr Hematol Oncol. 2013;35:e254–9.

    Article  PubMed  Google Scholar 

  58. Suganuma R, Wang LL, Sano H, Naranjo A, London WB, Seeger RC, Hogarty MD, Gastier-Foster JM, Look AT, Park JR, Maris JM, Cohn SL, Amann G, Beiske K, Cullinane CJ, d’Amore ES, Gambini C, Jarzembowski JA, Joshi VV, Navarro S, Peuchmaur M, Shimada H. Peripheral neuroblastic tumors with genotype-phenotype discordance: a report from the Children’s Oncology Group and the International Neuroblastoma Pathology Committee. Pediatr Blood Cancer. 2013;60:363–70.

    Article  PubMed  Google Scholar 

  59. Wang LL, Teshiba R, Ikegaki N, Tang XX, Naranjo A, London WB, Hogarty MD, Gastier-Foster JM, Look AT, Park JR, Maris JM, Cohn SL, Seeger RC, Asgharzadeh S, Shimada H. Augmented expression of MYC and/or MYCN protein defines highly aggressive MYC-driven neuroblastoma: a Children’s Oncology Group study. Br J Cancer. 2015;113:57–63.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  60. Bywater MJ, Pearson RB, McArthur GA, Hannan RD. Dysregulation of the basal RNA polymerase transcription apparatus in cancer. Nat Rev Cancer. 2013;13:299–314.

    Article  CAS  PubMed  Google Scholar 

  61. Darnell JE Jr. Transcription factors as targets for cancer therapy. Nat Rev Cancer. 2002;2:740–9.

    Article  CAS  PubMed  Google Scholar 

  62. Delmore JE, Issa GC, Lemieux ME, Rahl PB, Shi J, Jacobs HM, Kastritis E, Gilpatrick T, Paranal RM, Qi J, Chesi M, Schinzel AC, McKeown MR, Heffernan TP, Vakoc CR, Bergsagel PL, Ghobrial IM, Richardson PG, Young RA, Hahn WC, Anderson KC, Kung AL, Bradner JE, Mitsiades CS. BET bromodomain inhibition as a therapeutic strategy to target c-Myc. Cell. 2011;146:904–17.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  63. Puissant A, Frumm SM, Alexe G, Bassil CF, Qi J, Chanthery YH, Nekritz EA, Zeid R, Gustafson WC, Greninger P, Garnett MJ, McDermott U, Benes CH, Kung AL, Weiss WA, Bradner JE, Stegmaier K. Targeting MYCN in neuroblastoma by BET bromodomain inhibition. Cancer Discov. 2013;3:308–23.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  64. Gustafson WC, Meyerowitz JG, Nekritz EA, Chen J, Benes C, Charron E, Simonds EF, Seeger R, Matthay KK, Hertz NT, Eilers M, Shokat KM, Weiss WA. Drugging MYCN through an allosteric transition in Aurora kinase A. Cancer Cell. 2014;26:414–27.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  65. Hein N, Hannan KM, George AJ, Sanij E, Hannan RD. The nucleolus: an emerging target for cancer therapy. Trends Mol Med. 2013;19:643–54.

    Article  CAS  PubMed  Google Scholar 

  66. de Jonge MJ, Dumez H, Verweij J, Yarkoni S, Snyder D, Lacombe D, Marréaud S, Yamaguchi T, Punt CJ, van Oosterom A, EORTC New Drug Development Group (NDDG). Phase I and pharmacokinetic study of halofuginone, an oral quinazolinone derivative in patients with advanced solid tumours. Eur J Cancer. 2006;42:1768–74.

    Article  CAS  PubMed  Google Scholar 

  67. Drygin D, Lin A, Bliesath J, Ho CB, O’Brien SE, Proffitt C, Omori M, Haddach M, Schwaebe MK, Siddiqui-Jain A, Streiner N, Quin JE, Sanij E, Bywater MJ, Hannan RD, Ryckman D, Anderes K, Rice WG. Targeting RNA polymerase I with an oral small molecule CX-5461 inhibits ribosomal RNA synthesis and solid tumor growth. Cancer Res. 2011;71:1418–30.

    Article  CAS  PubMed  Google Scholar 

  68. Dai MS, Arnold H, Sun XX, Sears R, Lu H. Inhibition of c-Myc activity by ribosomal protein L11. EMBO J. 2007;26:3332–45.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  69. Liao JM, Zhou X, Gatignol A, Lu H. Ribosomal proteins L5 and L11 co-operatively inactivate c-Myc via RNA-induced silencing complex. Oncogene. 2014;33:4916–23.

    Article  CAS  PubMed  Google Scholar 

  70. Keller TL, Zocco D, Sundrud MS, Hendrick M, Edenius M, Yum J, Kim YJ, Lee HK, Cortese JF, Wirth DF, Dignam JD, Rao A, Yeo CY, Mazitschek R, Whitman M. Halofuginone and other febrifugine derivatives inhibit prolyl-tRNA synthetase. Nat Chem Biol. 2012;8:311–7.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  71. Sundrud MS, Koralov SB, Feuerer M, Calado DP, Kozhaya AE, Rhule-Smith A, Lefebvre RE, Unutmaz D, Mazitschek R, Waldner H, Whitman M, Keller T, Rao A. Halofuginone inhibits TH17 cell differentiation by activating the amino acid starvation response. Science. 2009;324(5932):1334–8.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  72. Kim DG, Lee JY, Lee JH, Cho HY, Kang BS, Jang SY, Kim MH, Guo M, Han JM, Kim SJ, Kim S. Oncogenic mutation of AIMP2/p38 inhibits its tumor-suppressive interaction with Smurf2. Cancer Res. 2016;76:3422–36.

    Article  CAS  PubMed  Google Scholar 

  73. Zhou W, Chung YJ, Parrilla Castellar ER, Zheng Y, Chung HJ, Bandle R, Liu J, Tessarollo L, Batchelor E, Aplan PD, Levens D. Far upstream element binding protein plays a crucial role in embryonic development, hematopoiesis, and stabilizing Myc expression levels. Am J Pathol. 2016;186:701–15.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  74. Taylor MD, Northcott PA, Korshunov A, Remke M, Cho YJ, Clifford SC, Eberhart CG, Parsons DW, Rutkowski S, Gajjar A, Ellison DW, Lichter P, Gilbertson RJ, Pomeroy SL, Kool M, Pfister SM. Molecular subgroups of medulloblastoma: the current consensus. Acta Neuropathol. 2012;123:465–72.

    Article  CAS  PubMed  Google Scholar 

  75. Fredlund E, Ringnér M, Maris JM, Påhlman S. High Myc pathway activity and low stage of neuronal differentiation associate with poor outcome in neuroblastoma. Proc Natl Acad Sci U S A. 2008;105:14094–9.

    Article  PubMed  PubMed Central  Google Scholar 

  76. Westermann F, Muth D, Benner A, Bauer T, Henrich KO, Oberthuer A, Brors B, Beissbarth T, Vandesompele J, Pattyn F, Hero B, König R, Fischer M, Schwab M. Distinct transcriptional MYCN/c-MYC activities are associated with spontaneous regression or malignant progression in neuroblastomas. Genome Biol. 2008;9:R150.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Pathology and Laboratory Medicine, Children’s Hospital Los Angeles, University of Southern California, Keck School of Medicine, Los Angeles, CA, USA

    Hiroyuki Shimada MD, PhD

  2. Department of Anatomy and Cell Biology, University of Illinois at Chicago, Chicago, IL, USA

    Naohiko Ikegaki PhD

Authors
  1. Hiroyuki Shimada MD, PhD
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Naohiko Ikegaki PhD
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Hiroyuki Shimada MD, PhD .

Editor information

Editors and Affiliations

  1. Department of Pathology, University of Utah/ARUP Laboratories, Salt Lake City, Utah, USA

    Larissa V. Furtado

  2. Department of Pathology, University of Chicago, Chicago, Illinois, USA

    Aliya N. Husain

Rights and permissions

Reprints and permissions

Copyright information

© 2018 Springer International Publishing AG, part of Springer Nature

About this chapter

Check for updates. Verify currency and authenticity via CrossMark

Cite this chapter

Shimada, H., Ikegaki, N. (2018). Neuroblastoma and Neuroblastic Tumors. In: Furtado, L., Husain, A. (eds) Precision Molecular Pathology of Neoplastic Pediatric Diseases . Molecular Pathology Library. Springer, Cham. https://doi.org/10.1007/978-3-319-89626-7_8

Download citation

  • DOI: https://doi.org/10.1007/978-3-319-89626-7_8

  • Published:

  • Publisher Name: Springer, Cham

  • Print ISBN: 978-3-319-89625-0

  • Online ISBN: 978-3-319-89626-7

  • eBook Packages: MedicineMedicine (R0)

Publish with us

Policies and ethics

Search

Navigation