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Neuroblastoma and Neuroblastic Tumors

  • Hiroyuki Shimada
  • Naohiko Ikegaki
Chapter
Part of the Molecular Pathology Library book series (MPLB)

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.

Keywords

Neuroblastoma DNA content Segmental chromosomal loss/gain MYCN oncogene ALK mutations/amplification TERT rearrangements ATRX mutations Chromothripsis Large-cell neuroblastoma MYC family-driven neuroblastoma 

References

  1. 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.CrossRefGoogle Scholar
  2. 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. 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. 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.CrossRefPubMedPubMedCentralGoogle Scholar
  5. 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.CrossRefGoogle Scholar
  6. 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.CrossRefPubMedPubMedCentralGoogle Scholar
  7. 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.CrossRefPubMedPubMedCentralGoogle Scholar
  8. 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.CrossRefGoogle Scholar
  9. 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.CrossRefPubMedPubMedCentralGoogle Scholar
  10. 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.CrossRefGoogle Scholar
  11. 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.CrossRefPubMedPubMedCentralGoogle Scholar
  12. 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.CrossRefPubMedGoogle Scholar
  13. 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.CrossRefPubMedPubMedCentralGoogle Scholar
  14. 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.CrossRefPubMedGoogle Scholar
  15. 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.PubMedGoogle Scholar
  16. 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.CrossRefPubMedPubMedCentralGoogle Scholar
  17. 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.CrossRefPubMedPubMedCentralGoogle Scholar
  18. 18.
    Maris JM. Recent advances in neuroblastoma. N Engl J Med. 2010;362:2202–11.CrossRefPubMedPubMedCentralGoogle Scholar
  19. 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.CrossRefPubMedPubMedCentralGoogle Scholar
  20. 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.CrossRefPubMedPubMedCentralGoogle Scholar
  21. 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.CrossRefPubMedPubMedCentralGoogle Scholar
  22. 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.CrossRefPubMedPubMedCentralGoogle Scholar
  23. 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.CrossRefGoogle Scholar
  24. 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.CrossRefPubMedGoogle Scholar
  25. 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.CrossRefPubMedPubMedCentralGoogle Scholar
  26. 26.
    Mosse YP. Anaplastic lymphoma kinase as a cancer target in pediatric malignancies. Clin Cancer Res. 2016;22:546–52.CrossRefPubMedGoogle Scholar
  27. 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.CrossRefPubMedPubMedCentralGoogle Scholar
  28. 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.CrossRefPubMedPubMedCentralGoogle Scholar
  29. 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.CrossRefPubMedGoogle Scholar
  30. 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.CrossRefPubMedPubMedCentralGoogle Scholar
  31. 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.CrossRefPubMedGoogle Scholar
  32. 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.CrossRefPubMedGoogle Scholar
  33. 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.CrossRefPubMedPubMedCentralGoogle Scholar
  34. 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.CrossRefPubMedPubMedCentralGoogle Scholar
  35. 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.CrossRefPubMedPubMedCentralGoogle Scholar
  36. 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.CrossRefPubMedGoogle Scholar
  37. 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.CrossRefPubMedGoogle Scholar
  38. 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.CrossRefPubMedPubMedCentralGoogle Scholar
  39. 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.CrossRefPubMedGoogle Scholar
  40. 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.CrossRefGoogle Scholar
  41. 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.CrossRefGoogle Scholar
  42. 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.CrossRefPubMedGoogle Scholar
  43. 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.CrossRefPubMedPubMedCentralGoogle Scholar
  44. 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.CrossRefPubMedPubMedCentralGoogle Scholar
  45. 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.CrossRefGoogle Scholar
  46. 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.CrossRefPubMedGoogle Scholar
  47. 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.CrossRefPubMedPubMedCentralGoogle Scholar
  48. 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.CrossRefPubMedPubMedCentralGoogle Scholar
  49. 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.CrossRefPubMedGoogle Scholar
  50. 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.CrossRefPubMedGoogle Scholar
  51. 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.CrossRefPubMedGoogle Scholar
  52. 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.CrossRefPubMedPubMedCentralGoogle Scholar
  53. 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.CrossRefPubMedPubMedCentralGoogle Scholar
  54. 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.CrossRefPubMedGoogle Scholar
  55. 55.
    Davidoff AM. Neuroblastoma. Semin Pediatr Surg. 2012;21:2–14.CrossRefPubMedPubMedCentralGoogle Scholar
  56. 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.CrossRefPubMedPubMedCentralGoogle Scholar
  57. 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.CrossRefPubMedGoogle Scholar
  58. 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.CrossRefPubMedGoogle Scholar
  59. 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.CrossRefPubMedPubMedCentralGoogle Scholar
  60. 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.CrossRefPubMedGoogle Scholar
  61. 61.
    Darnell JE Jr. Transcription factors as targets for cancer therapy. Nat Rev Cancer. 2002;2:740–9.CrossRefPubMedGoogle Scholar
  62. 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.CrossRefPubMedPubMedCentralGoogle Scholar
  63. 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.CrossRefPubMedPubMedCentralGoogle Scholar
  64. 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.CrossRefPubMedPubMedCentralGoogle Scholar
  65. 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.CrossRefPubMedGoogle Scholar
  66. 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.CrossRefPubMedGoogle Scholar
  67. 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.CrossRefPubMedGoogle Scholar
  68. 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.CrossRefPubMedPubMedCentralGoogle Scholar
  69. 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.CrossRefPubMedGoogle Scholar
  70. 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.CrossRefPubMedPubMedCentralGoogle Scholar
  71. 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.CrossRefPubMedPubMedCentralGoogle Scholar
  72. 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.CrossRefPubMedGoogle Scholar
  73. 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.CrossRefPubMedPubMedCentralGoogle Scholar
  74. 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.CrossRefPubMedGoogle Scholar
  75. 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.CrossRefPubMedPubMedCentralGoogle Scholar
  76. 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.CrossRefPubMedPubMedCentralGoogle Scholar

Copyright information

© Springer International Publishing AG, part of Springer Nature 2018

Authors and Affiliations

  1. 1.Department of Pathology and Laboratory MedicineChildren’s Hospital Los Angeles, University of Southern California, Keck School of MedicineLos AngelesUSA
  2. 2.Department of Anatomy and Cell BiologyUniversity of Illinois at ChicagoChicagoUSA

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