Pediatric Surgery International

, Volume 29, Issue 2, pp 101–119 | Cite as

The role of genetic and epigenetic alterations in neuroblastoma disease pathogenesis

  • Raquel Domingo-Fernandez
  • Karen Watters
  • Olga Piskareva
  • Raymond L. StallingsEmail author
  • Isabella Bray
Review Article


Neuroblastoma is a highly heterogeneous tumor accounting for 15 % of all pediatric cancer deaths. Clinical behavior ranges from the spontaneous regression of localized, asymptomatic tumors, as well as metastasized tumors in infants, to rapid progression and resistance to therapy. Genomic amplification of the MYCN oncogene has been used to predict outcome in neuroblastoma for over 30 years, however, recent methodological advances including miRNA and mRNA profiling, comparative genomic hybridization (array-CGH), and whole-genome sequencing have enabled the detailed analysis of the neuroblastoma genome, leading to the identification of new prognostic markers and better patient stratification. In this review, we will describe the main genetic factors responsible for these diverse clinical phenotypes in neuroblastoma, the chronology of their discovery, and the impact on patient prognosis.


Neuroblastoma MYCN MiRNA DNA methylation ALK PTPRD 


  1. 1.
    Spix C et al (2006) Neuroblastoma incidence and survival in European children (1978–1997): report from the Automated Childhood Cancer Information System project. Eur J Cancer 42(13):2081–2091PubMedCrossRefGoogle Scholar
  2. 2.
    Gurney JG et al (1995) Incidence of cancer in children in the United States. Sex-, race-, and 1-year age-specific rates by histologic type. Cancer 75(8):2186–2195PubMedCrossRefGoogle Scholar
  3. 3.
    Brodeur GM (2003) Neuroblastoma: biological insights into a clinical enigma. Nat Rev Cancer 3(3):203–216PubMedCrossRefGoogle Scholar
  4. 4.
    Brodeur GM et al (1984) Amplification of N-myc in untreated human neuroblastomas correlates with advanced disease stage. Science 224(4653):1121–1124PubMedCrossRefGoogle Scholar
  5. 5.
    Mosse YP et al (2004) Germline PHOX2B mutation in hereditary neuroblastoma. Am J Hum Genet 75(4):727–730PubMedCrossRefGoogle Scholar
  6. 6.
    Mosse YP et al (2008) Identification of ALK as a major familial neuroblastoma predisposition gene. Nature 455(7215):930–935PubMedCrossRefGoogle Scholar
  7. 7.
    Chen Y et al (2008) Oncogenic mutations of ALK kinase in neuroblastoma. Nature 455(7215):971–974PubMedCrossRefGoogle Scholar
  8. 8.
    Stallings RL et al (2006) High-resolution analysis of chromosomal breakpoints and genomic instability identifies PTPRD as a candidate tumor suppressor gene in neuroblastoma. Cancer Res 66(7):3673–3680PubMedCrossRefGoogle Scholar
  9. 9.
    Molenaar JJ et al (2012) Sequencing of neuroblastoma identifies chromothripsis and defects in neuritogenesis genes. Nature 483(7391):589–593PubMedCrossRefGoogle Scholar
  10. 10.
    Asgharzadeh S et al (2006) Prognostic significance of gene expression profiles of metastatic neuroblastomas lacking MYCN gene amplification. J Natl Cancer Inst 98(17):1193–1203PubMedCrossRefGoogle Scholar
  11. 11.
    Vermeulen J et al (2009) Predicting outcomes for children with neuroblastoma using a multigene-expression signature: a retrospective SIOPEN/COG/GPOH study. Lancet Oncol 10(7):663–671PubMedCrossRefGoogle Scholar
  12. 12.
    De Preter K et al (2010) Accurate outcome prediction in neuroblastoma across independent data sets using a multigene signature. Clin Cancer Res 16(5):1532–1541PubMedCrossRefGoogle Scholar
  13. 13.
    Oberthuer A et al (2008) Subclassification and individual survival time prediction from gene expression data of neuroblastoma patients by using CASPAR. Clin Cancer Res 14(20):6590–6601PubMedCrossRefGoogle Scholar
  14. 14.
    Ohira M, Nakagawara A (2010) Global genomic and RNA profiles for novel risk stratification of neuroblastoma. Cancer Sci 101(11):2295–2301PubMedCrossRefGoogle Scholar
  15. 15.
    Chen Y, Stallings RL (2007) Differential patterns of microRNA expression in neuroblastoma are correlated with prognosis, differentiation, and apoptosis. Cancer Res 67(3):976–983PubMedCrossRefGoogle Scholar
  16. 16.
    Bray I et al (2009) Widespread dysregulation of MiRNAs by MYCN amplification and chromosomal imbalances in neuroblastoma: association of miRNA expression with survival. PLoS One 4(11):e7850PubMedCrossRefGoogle Scholar
  17. 17.
    Cohn SL et al (2009) The International Neuroblastoma Risk Group (INRG) classification system: an INRG Task Force report. J Clin Oncol 27(2):289–297PubMedCrossRefGoogle Scholar
  18. 18.
    Kaneko Y et al (1987) Different karyotypic patterns in early and advanced stage neuroblastomas. Cancer Res 47(1):311–318PubMedGoogle Scholar
  19. 19.
    Brodeur GM, Nakagawara A (1992) Molecular basis of clinical heterogeneity in neuroblastoma. Am J Pediatr Hematol Oncol 14(2):111–116PubMedCrossRefGoogle Scholar
  20. 20.
    Kaneko Y, Knudson AG (2000) Mechanism and relevance of ploidy in neuroblastoma. Genes Chromosomes Cancer 29(2):89–95PubMedCrossRefGoogle Scholar
  21. 21.
    Brodeur GM et al (1997) Biology and genetics of human neuroblastomas. J Pediatr Hematol Oncol 19(2):93–101PubMedCrossRefGoogle Scholar
  22. 22.
    Schleiermacher G et al (2012) Segmental chromosomal alterations have prognostic impact in neuroblastoma: a report from the INRG project. Br J Cancer 107(8):1418–1422PubMedCrossRefGoogle Scholar
  23. 23.
    Seeger RC et al (1985) Association of multiple copies of the N-myc oncogene with rapid progression of neuroblastomas. N Engl J Med 313(18):1111–1116PubMedCrossRefGoogle Scholar
  24. 24.
    Lutz W et al (1996) Conditional expression of N-myc in human neuroblastoma cells increases expression of alpha-prothymosin and ornithine decarboxylase and accelerates progression into S-phase early after mitogenic stimulation of quiescent cells. Oncogene 13(4):803–812PubMedGoogle Scholar
  25. 25.
    Schweigerer L et al (1990) Augmented MYCN expression advances the malignant phenotype of human neuroblastoma cells: evidence for induction of autocrine growth factor activity. Cancer Res 50(14):4411–4416PubMedGoogle Scholar
  26. 26.
    Knoepfler PS, Cheng PF, Eisenman RN (2002) N-myc is essential during neurogenesis for the rapid expansion of progenitor cell populations and the inhibition of neuronal differentiation. Genes Dev 16(20):2699–2712PubMedCrossRefGoogle Scholar
  27. 27.
    Giannini G et al (2005) High mobility group A1 is a molecular target for MYCN in human neuroblastoma. Cancer Res 65(18):8308–8316PubMedCrossRefGoogle Scholar
  28. 28.
    Shohet JM et al (2002) Minichromosome maintenance protein MCM7 is a direct target of the MYCN transcription factor in neuroblastoma. Cancer Res 62(4):1123–1128PubMedGoogle Scholar
  29. 29.
    Slack A et al (2005) The p53 regulatory gene MDM2 is a direct transcriptional target of MYCN in neuroblastoma. Proc Natl Acad Sci USA 102(3):731–736PubMedCrossRefGoogle Scholar
  30. 30.
    Chen L et al (2010) p53 is a direct transcriptional target of MYCN in neuroblastoma. Cancer Res 70(4):1377–1388PubMedCrossRefGoogle Scholar
  31. 31.
    Manohar CF et al (2004) MYCN-mediated regulation of the MRP1 promoter in human neuroblastoma. Oncogene 23(3):753–762PubMedCrossRefGoogle Scholar
  32. 32.
    Weiss WA et al (1997) Targeted expression of MYCN causes neuroblastoma in transgenic mice. EMBO J 16(11):2985–2995PubMedCrossRefGoogle Scholar
  33. 33.
    Edsjo A et al (2004) Neuroblastoma cells with overexpressed MYCN retain their capacity to undergo neuronal differentiation. Lab Invest 84(4):406–417PubMedCrossRefGoogle Scholar
  34. 34.
    Chan HS et al (1997) MYCN protein expression as a predictor of neuroblastoma prognosis. Clin Cancer Res 3(10):1699–1706PubMedGoogle Scholar
  35. 35.
    Valentijn LJ et al (2012) Functional MYCN signature predicts outcome of neuroblastoma irrespective of MYCN amplification. Proc Natl Acad Sci USA 109(47):19190–19195PubMedCrossRefGoogle Scholar
  36. 36.
    Brodeur GM, Fong CT (1989) Molecular biology and genetics of human neuroblastoma. Cancer Genet Cytogenet 41(2):153–174PubMedCrossRefGoogle Scholar
  37. 37.
    Brodeur GM et al (1981) Cytogenetic features of human neuroblastomas and cell lines. Cancer Res 41(11 Pt 1):4678–4686PubMedGoogle Scholar
  38. 38.
    Fong CT et al (1989) Loss of heterozygosity for the short arm of chromosome 1 in human neuroblastomas: correlation with N-myc amplification. Proc Natl Acad Sci USA 86(10):3753–3757PubMedCrossRefGoogle Scholar
  39. 39.
    Attiyeh EF et al (2005) Chromosome 1p and 11q deletions and outcome in neuroblastoma. N Engl J Med 353(21):2243–2253PubMedCrossRefGoogle Scholar
  40. 40.
    Martinsson T et al (1997) Delimitation of a critical tumour suppressor region at distal 1p in neuroblastoma tumours. Eur J Cancer 33(12):1997–2001PubMedCrossRefGoogle Scholar
  41. 41.
    Bauer A et al (2001) Smallest region of overlapping deletion in 1p36 in human neuroblastoma: a 1 Mbp cosmid and PAC contig. Genes Chromosomes Cancer 31(3):228–239PubMedCrossRefGoogle Scholar
  42. 42.
    Ohira M et al (2000) Identification and characterization of a 500-kb homozygously deleted region at 1p36.2–p36.3 in a neuroblastoma cell line. Oncogene 19(37):4302–4307PubMedCrossRefGoogle Scholar
  43. 43.
    Thompson PM et al (2003) CHD5, a new member of the chromodomain gene family, is preferentially expressed in the nervous system. Oncogene 22(7):1002–1011PubMedCrossRefGoogle Scholar
  44. 44.
    Fujita T et al (2008) CHD5, a tumor suppressor gene deleted from 1p36.31 in neuroblastomas. J Natl Cancer Inst 100(13):940–949PubMedCrossRefGoogle Scholar
  45. 45.
    Koyama H et al (2012) Mechanisms of CHD5 inactivation in neuroblastomas. Clin Cancer Res 18(6):1588–1597PubMedCrossRefGoogle Scholar
  46. 46.
    Henrich KO et al (2006) Reduced expression of CAMTA1 correlates with adverse outcome in neuroblastoma patients. Clin Cancer Res 12(1):131–138PubMedCrossRefGoogle Scholar
  47. 47.
    Henrich KO et al (2011) CAMTA1, a 1p36 tumor suppressor candidate, inhibits growth and activates differentiation programs in neuroblastoma cells. Cancer Res 71(8):3142–3151PubMedCrossRefGoogle Scholar
  48. 48.
    Liu Z et al (2011) CASZ1, a candidate tumor-suppressor gene, suppresses neuroblastoma tumor growth through reprogramming gene expression. Cell Death Differ 18(7):1174–1183PubMedCrossRefGoogle Scholar
  49. 49.
    Wang C et al (2012) EZH2 mediates epigenetic silencing of neuroblastoma suppressor genes CASZ1, CLU, RUNX3, and NGFR. Cancer Res 72(1):315–324PubMedCrossRefGoogle Scholar
  50. 50.
    Krona C et al (2003) Screening for gene mutations in a 500 kb neuroblastoma tumor suppressor candidate region in chromosome 1p; mutation and stage-specific expression in UBE4B/UFD2. Oncogene 22(15):2343–2351PubMedCrossRefGoogle Scholar
  51. 51.
    Krona C et al (2004) A novel 1p36.2 located gene, APITD1, with tumour-suppressive properties and a putative p53-binding domain, shows low expression in neuroblastoma tumours. Br J Cancer 91(6):1119–1130PubMedGoogle Scholar
  52. 52.
    Guo C et al (1999) Allelic deletion at 11q23 is common in MYCN single copy neuroblastomas. Oncogene 18(35):4948–4957PubMedCrossRefGoogle Scholar
  53. 53.
    Plantaz D et al (2001) Comparative genomic hybridization (CGH) analysis of stage 4 neuroblastoma reveals high frequency of 11q deletion in tumors lacking MYCN amplification. Int J Cancer 91(5):680–686PubMedCrossRefGoogle Scholar
  54. 54.
    Maris JM et al (2001) Allelic deletion at chromosome bands 11q14–23 is common in neuroblastoma. Med Pediatr Oncol 36(1):24–27PubMedCrossRefGoogle Scholar
  55. 55.
    Spitz R et al (2006) Loss in chromosome 11q identifies tumors with increased risk for metastatic relapses in localized and 4S neuroblastoma. Clin Cancer Res 12(11 Pt 1):3368–3373PubMedCrossRefGoogle Scholar
  56. 56.
    Michels E et al (2007) ArrayCGH-based classification of neuroblastoma into genomic subgroups. Genes Chromosomes Cancer 46(12):1098–1108PubMedCrossRefGoogle Scholar
  57. 57.
    Luttikhuis ME et al (2001) Neuroblastomas with chromosome 11q loss and single copy MYCN comprise a biologically distinct group of tumours with adverse prognosis. Br J Cancer 85(4):531–537PubMedCrossRefGoogle Scholar
  58. 58.
    Caren H et al (2010) High-risk neuroblastoma tumors with 11q− deletion display a poor prognostic, chromosome instability phenotype with later onset. Proc Natl Acad Sci USA 107(9):4323–4328PubMedCrossRefGoogle Scholar
  59. 59.
    Celeste A et al (2003) H2AX haploinsufficiency modifies genomic stability and tumor susceptibility. Cell 114(3):371–383PubMedCrossRefGoogle Scholar
  60. 60.
    Nowacki S et al (2008) Expression of the tumour suppressor gene CADM1 is associated with favourable outcome and inhibits cell survival in neuroblastoma. Oncogene 27(23):3329–3338PubMedCrossRefGoogle Scholar
  61. 61.
    Michels E et al (2008) CADM1 is a strong neuroblastoma candidate gene that maps within a 3.72 Mb critical region of loss on 11q23. BMC Cancer 8:173PubMedCrossRefGoogle Scholar
  62. 62.
    Ando K et al (2008) Expression of TSLC1, a candidate tumor suppressor gene mapped to chromosome 11q23, is downregulated in unfavorable neuroblastoma without promoter hypermethylation. Int J Cancer 123(9):2087–2094PubMedCrossRefGoogle Scholar
  63. 63.
    Bown NP, Pearson AD, Reid MM (1993) High incidence of constitutional balanced translocations in neuroblastoma. Cancer Genet Cytogenet 69(2):166–167PubMedCrossRefGoogle Scholar
  64. 64.
    Koiffmann CP et al (1995) Neuroblastoma in a boy with MCA/MR syndrome, deletion 11q, and duplication 12q. Am J Med Genet 58(1):46–49PubMedCrossRefGoogle Scholar
  65. 65.
    Schulte JH et al (2010) Accurate prediction of neuroblastoma outcome based on miRNA expression profiles. Int J Cancer 127(10):2374–2385PubMedCrossRefGoogle Scholar
  66. 66.
    Meddeb M et al (1996) Additional copies of a 25 Mb chromosomal region originating from 17q23.1–17qter are present in 90 % of high-grade neuroblastomas. Genes Chromosomes Cancer 17(3):156–165PubMedCrossRefGoogle Scholar
  67. 67.
    Caron H (1995) Allelic loss of chromosome 1 and additional chromosome 17 material are both unfavourable prognostic markers in neuroblastoma. Med Pediatr Oncol 24(4):215–221PubMedCrossRefGoogle Scholar
  68. 68.
    Bown N et al (1999) Gain of chromosome arm 17q and adverse outcome in patients with neuroblastoma. N Engl J Med 340(25):1954–1961PubMedCrossRefGoogle Scholar
  69. 69.
    Van Roy N et al (1995) Molecular cytogenetic analysis of 1;17 translocations in neuroblastoma. Eur J Cancer 31A(4):530–535PubMedGoogle Scholar
  70. 70.
    Lastowska M et al (1997) Promiscuous translocations of chromosome arm 17q in human neuroblastomas. Genes Chromosomes Cancer 19(3):143–149PubMedCrossRefGoogle Scholar
  71. 71.
    Savelyeva L, Corvi R, Schwab M (1994) Translocation involving 1p and 17q is a recurrent genetic alteration of human neuroblastoma cells. Am J Hum Genet 55(2):334–340PubMedGoogle Scholar
  72. 72.
    McConville CM et al (2001) Molecular cytogenetic characterization of two non-MYCN amplified neuroblastoma cell lines with complex t(11;17). Cancer Genet Cytogenet 130(2):133–140PubMedCrossRefGoogle Scholar
  73. 73.
    Stark B et al (2003) der(11)t(11;17): a distinct cytogenetic pathway of advanced stage neuroblastoma (NBL)—detected by spectral karyotyping (SKY). Cancer Lett 197(1–2):75–79PubMedCrossRefGoogle Scholar
  74. 74.
    Stallings RL et al (2004) Molecular cytogenetic analysis of recurrent unbalanced t(11;17) in neuroblastoma. Cancer Genet Cytogenet 154(1):44–51PubMedCrossRefGoogle Scholar
  75. 75.
    Schleiermacher G et al (2004) Variety and complexity of chromosome 17 translocations in neuroblastoma. Genes Chromosomes Cancer 39(2):143–150PubMedCrossRefGoogle Scholar
  76. 76.
    Spitz R et al (2003) Gain of distal chromosome arm 17q is not associated with poor prognosis in neuroblastoma. Clin Cancer Res 9(13):4835–4840PubMedGoogle Scholar
  77. 77.
    Brinkschmidt C et al (1997) Comparative genomic hybridization (CGH) analysis of neuroblastomas—an important methodological approach in paediatric tumour pathology. J Pathol 181(4):394–400PubMedCrossRefGoogle Scholar
  78. 78.
    Buckley PG et al (2010) Chromosomal and microRNA expression patterns reveal biologically distinct subgroups of 11q− neuroblastoma. Clin Cancer Res 16(11):2971–2978PubMedCrossRefGoogle Scholar
  79. 79.
    Claviez A et al (2004) Low occurrence of familial neuroblastomas and ganglioneuromas in five consecutive GPOH neuroblastoma treatment studies. Eur J Cancer 40(18):2760–2765PubMedCrossRefGoogle Scholar
  80. 80.
    Maris JM et al (1997) Molecular genetic analysis of familial neuroblastoma. Eur J Cancer 33(12):1923–1928PubMedCrossRefGoogle Scholar
  81. 81.
    Pattyn A et al (2000) Control of hindbrain motor neuron differentiation by the homeobox gene Phox2b. Development 127(7):1349–1358PubMedGoogle Scholar
  82. 82.
    Raabe EH et al (2008) Prevalence and functional consequence of PHOX2B mutations in neuroblastoma. Oncogene 27(4):469–476PubMedCrossRefGoogle Scholar
  83. 83.
    van Limpt V et al (2004) The Phox2B homeobox gene is mutated in sporadic neuroblastomas. Oncogene 23(57):9280–9288PubMedGoogle Scholar
  84. 84.
    Mano H (2012) ALKoma: a cancer subtype with a shared target. Cancer Discov 2(6):495–502PubMedCrossRefGoogle Scholar
  85. 85.
    Azarova AM, Gautam G, George RE (2011) Emerging importance of ALK in neuroblastoma. Semin Cancer Biol 21(4):267–275PubMedCrossRefGoogle Scholar
  86. 86.
    Heukamp LC et al (2012) Targeted Expression of Mutated ALK Induces Neuroblastoma in Transgenic Mice. Sci Transl Med 4(141):141ra91Google Scholar
  87. 87.
    Capasso M et al (2009) Common variations in BARD1 influence susceptibility to high-risk neuroblastoma. Nat Genet 41(6):718–723PubMedCrossRefGoogle Scholar
  88. 88.
    Wang K et al (2011) Integrative genomics identifies LMO1 as a neuroblastoma oncogene. Nature 469(7329):216–220PubMedCrossRefGoogle Scholar
  89. 89.
    Maris JM et al (2008) Chromosome 6p22 locus associated with clinically aggressive neuroblastoma. N Engl J Med 358(24):2585–2593PubMedCrossRefGoogle Scholar
  90. 90.
    Wu LC et al (1996) Identification of a RING protein that can interact in vivo with the BRCA1 gene product. Nat Genet 14(4):430–440PubMedCrossRefGoogle Scholar
  91. 91.
    Stephens PJ et al (2011) Massive genomic rearrangement acquired in a single catastrophic event during cancer development. Cell 144(1):27–40PubMedCrossRefGoogle Scholar
  92. 92.
    Diskin SJ et al (2012) Common variation at 6q16 within HACE1 and LIN28B influences susceptibility to neuroblastoma. Nat Genet 44(10):1126–1130PubMedCrossRefGoogle Scholar
  93. 93.
    Molenaar JJ et al (2012) LIN28B induces neuroblastoma and enhances MYCN levels via let-7 suppression. Nat Genet 44(11):1199–1206PubMedCrossRefGoogle Scholar
  94. 94.
    Fischer M et al (2006) Differential expression of neuronal genes defines subtypes of disseminated neuroblastoma with favorable and unfavorable outcome. Clin Cancer Res 12(17):5118–5128PubMedCrossRefGoogle Scholar
  95. 95.
    Berwanger B et al (2002) Loss of a FYN-regulated differentiation and growth arrest pathway in advanced stage neuroblastoma. Cancer Cell 2(5):377–386PubMedCrossRefGoogle Scholar
  96. 96.
    Oberthuer A et al (2006) Customized oligonucleotide microarray gene expression-based classification of neuroblastoma patients outperforms current clinical risk stratification. J Clin Oncol 24(31):5070–5078PubMedCrossRefGoogle Scholar
  97. 97.
    Ohira M et al (2005) Expression profiling using a tumor-specific cDNA microarray predicts the prognosis of intermediate risk neuroblastomas. Cancer Cell 7(4):337–350PubMedCrossRefGoogle Scholar
  98. 98.
    Wang Q et al (2006) Integrative genomics identifies distinct molecular classes of neuroblastoma and shows that multiple genes are targeted by regional alterations in DNA copy number. Cancer Res 66(12):6050–6062PubMedCrossRefGoogle Scholar
  99. 99.
    Abel F et al (2011) A 6-gene signature identifies four molecular subgroups of neuroblastoma. Cancer Cell Int 11:9PubMedCrossRefGoogle Scholar
  100. 100.
    Fischer M et al (2009) Integrated genomic profiling identifies two distinct molecular subtypes with divergent outcome in neuroblastoma with loss of chromosome 11q. Oncogene 29:865–875PubMedCrossRefGoogle Scholar
  101. 101.
    Lee RC, Feinbaum RL, Ambros V (1993) The C. elegans heterochronic gene lin-4 encodes small RNAs with antisense complementarity to lin-14. Cell 75(5):843–854PubMedCrossRefGoogle Scholar
  102. 102.
    Hebert SS, De Strooper B (2007) Molecular biology. miRNAs in neurodegeneration. Science 317(5842):1179–1180Google Scholar
  103. 103.
    Iorio MV et al (2005) MicroRNA gene expression deregulation in human breast cancer. Cancer Res 65(16):7065–7070PubMedCrossRefGoogle Scholar
  104. 104.
    Miska EA (2005) How microRNAs control cell division, differentiation and death. Curr Opin Genet Dev 15(5):563–568PubMedCrossRefGoogle Scholar
  105. 105.
    Kapsimali M et al (2007) MicroRNAs show a wide diversity of expression profiles in the developing and mature central nervous system. Genome Biol 8(8):R173PubMedCrossRefGoogle Scholar
  106. 106.
    Lu J et al (2005) MicroRNA expression profiles classify human cancers. Nature 435(7043):834–838PubMedCrossRefGoogle Scholar
  107. 107.
    Schulte JH et al (2008) MYCN regulates oncogenic microRNAs in neuroblastoma. Int J Cancer 122(3):699–704PubMedCrossRefGoogle Scholar
  108. 108.
    Fontana L et al (2008) Antagomir-17-5p abolishes the growth of therapy-resistant neuroblastoma through p21 and BIM. PLoS One 3(5):e2236PubMedCrossRefGoogle Scholar
  109. 109.
    Mestdagh P et al (2010) The miR-17-92 microRNA cluster regulates multiple components of the TGF-beta pathway in neuroblastoma. Mol Cell 40(5):762–773PubMedCrossRefGoogle Scholar
  110. 110.
    De Brouwer S et al (2012) Dickkopf-3 is regulated by the MYCN-induced miR-17-92 cluster in neuroblastoma. Int J Cancer 130(11):2591–2598PubMedCrossRefGoogle Scholar
  111. 111.
    Buechner J et al (2011) Tumour-suppressor microRNAs let-7 and mir-101 target the proto-oncogene MYCN and inhibit cell proliferation in MYCN-amplified neuroblastoma. Br J Cancer 105(2):296–303PubMedCrossRefGoogle Scholar
  112. 112.
    Welch C, Chen Y, Stallings RL (2007) MicroRNA-34a functions as a potential tumor suppressor by inducing apoptosis in neuroblastoma cells. Oncogene 26(34):5017–5022PubMedCrossRefGoogle Scholar
  113. 113.
    Tivnan A et al (2011) MicroRNA-34a is a potent tumor suppressor molecule in vivo in neuroblastoma. BMC Cancer 11:33PubMedCrossRefGoogle Scholar
  114. 114.
    Cole KA et al (2008) A functional screen identifies miR-34a as a candidate neuroblastoma tumor suppressor gene. Mol Cancer Res 6(5):735–742PubMedCrossRefGoogle Scholar
  115. 115.
    Lynch J et al (2012) MiRNA-335 suppresses neuroblastoma cell invasiveness by direct targeting of multiple genes from the non-canonical TGF-beta signalling pathway. Carcinogenesis 33(5):976–985PubMedCrossRefGoogle Scholar
  116. 116.
    Bray I et al (2011) MicroRNA-542-5p as a novel tumor suppressor in neuroblastoma. Cancer Lett 303(1):56–64PubMedCrossRefGoogle Scholar
  117. 117.
    Laneve P et al (2007) The interplay between microRNAs and the neurotrophin receptor tropomyosin-related kinase C controls proliferation of human neuroblastoma cells. Proc Natl Acad Sci USA 104(19):7957–7962PubMedCrossRefGoogle Scholar
  118. 118.
    Le MT et al (2009) MicroRNA-125b promotes neuronal differentiation in human cells by repressing multiple targets. Mol Cell Biol 29(19):5290–5305PubMedCrossRefGoogle Scholar
  119. 119.
    Foley NH et al (2011) MicroRNAs 10a and 10b are potent inducers of neuroblastoma cell differentiation through targeting of nuclear receptor corepressor 2. Cell Death Differ 18(7):1089–1098PubMedCrossRefGoogle Scholar
  120. 120.
    Ryan J et al (2012) MicroRNA-204 increases sensitivity of neuroblastoma cells to cisplatin and is associated with a favourable clinical outcome. Br J Cancer 107(6):967–976PubMedCrossRefGoogle Scholar
  121. 121.
    Calin GA et al (2004) Human microRNA genes are frequently located at fragile sites and genomic regions involved in cancers. Proc Natl Acad Sci USA 101(9):2999–3004PubMedCrossRefGoogle Scholar
  122. 122.
    Chang TC et al (2007) Transactivation of miR-34a by p53 broadly influences gene expression and promotes apoptosis. Mol Cell 26(5):745–752PubMedCrossRefGoogle Scholar
  123. 123.
    Wei JS et al (2008) The MYCN oncogene is a direct target of miR-34a. Oncogene 27(39):5204–5213PubMedCrossRefGoogle Scholar
  124. 124.
    Tivnan A et al (2012) Inhibition of neuroblastoma tumor growth by targeted delivery of microRNA-34a using anti-disialoganglioside GD2 coated nanoparticles. PLoS One 7(5):e38129PubMedCrossRefGoogle Scholar
  125. 125.
    Bommer GT et al (2007) p53-mediated activation of miRNA34 candidate tumor-suppressor genes. Curr Biol 17(15):1298–1307PubMedCrossRefGoogle Scholar
  126. 126.
    Sun F et al (2008) Downregulation of CCND1 and CDK6 by miR-34a induces cell cycle arrest. FEBS Lett 582(10):1564–1568PubMedCrossRefGoogle Scholar
  127. 127.
    Atroshchenko ES et al (1991) Effect of xanthinol niacinate on the autoimmunity and capillary permeability in patients with stable stenocardia. Kardiologiia 31(3):18–21PubMedGoogle Scholar
  128. 128.
    Pang RT et al (2010) MicroRNA-34a suppresses invasion through downregulation of Notch1 and Jagged1 in cervical carcinoma and choriocarcinoma cells. Carcinogenesis 31(6):1037–1044PubMedCrossRefGoogle Scholar
  129. 129.
    Brodeur GM et al (1988) International criteria for diagnosis, staging, and response to treatment in patients with neuroblastoma. J Clin Oncol 6(12):1874–1881PubMedGoogle Scholar
  130. 130.
    Mestdagh P et al (2010) MYCN/c-MYC-induced microRNAs repress coding gene networks associated with poor outcome in MYCN/c-MYC-activated tumors. Oncogene 29(9):1394–1404PubMedCrossRefGoogle Scholar
  131. 131.
    Murphy DM et al (2009) Global MYCN transcription factor binding analysis in neuroblastoma reveals association with distinct E-box motifs and regions of DNA hypermethylation. PLoS One 4(12):e8154PubMedCrossRefGoogle Scholar
  132. 132.
    Corcoran DL et al (2009) Features of mammalian microRNA promoters emerge from polymerase II chromatin immunoprecipitation data. PLoS One 4(4):e5279PubMedCrossRefGoogle Scholar
  133. 133.
    Shohet JM et al (2011) A genome-wide search for promoters that respond to increased MYCN reveals both new oncogenic and tumor suppressor microRNAs associated with aggressive neuroblastoma. Cancer Res 71(11):3841–3851PubMedCrossRefGoogle Scholar
  134. 134.
    Hayashita Y et al (2005) A polycistronic microRNA cluster, miR-17-92, is overexpressed in human lung cancers and enhances cell proliferation. Cancer Res 65(21):9628–9632PubMedCrossRefGoogle Scholar
  135. 135.
    Busacca S et al (2009) MicroRNA signature of malignant mesothelioma with potential diagnostic and prognostic implications. Am J Respir Cell Mol Biol 42:312–319Google Scholar
  136. 136.
    Yu Z et al (2008) A cyclin D1/microRNA 17/20 regulatory feedback loop in control of breast cancer cell proliferation. J Cell Biol 182(3):509–517PubMedCrossRefGoogle Scholar
  137. 137.
    Mraz M et al (2009) MicroRNAs in chronic lymphocytic leukemia pathogenesis and disease subtypes. Leuk Lymphoma 50(3):506–509PubMedCrossRefGoogle Scholar
  138. 138.
    Takakura S et al (2008) Oncogenic role of miR-17-92 cluster in anaplastic thyroid cancer cells. Cancer Sci 99(6):1147–1154PubMedCrossRefGoogle Scholar
  139. 139.
    O’Donnell KA et al (2005) c-Myc-regulated microRNAs modulate E2F1 expression. Nature 435(7043):839–843PubMedCrossRefGoogle Scholar
  140. 140.
    He L et al (2007) A microRNA component of the p53 tumour suppressor network. Nature 447(7148):1130–1134PubMedCrossRefGoogle Scholar
  141. 141.
    Braun CJ et al (2008) p53-Responsive microRNAs 192 and 215 are capable of inducing cell cycle arrest. Cancer Res 68(24):10094–10104PubMedCrossRefGoogle Scholar
  142. 142.
    Sachdeva M et al (2009) p53 represses c-Myc through induction of the tumor suppressor miR-145. Proc Natl Acad Sci USA 106(9):3207–3212PubMedCrossRefGoogle Scholar
  143. 143.
    Georges SA et al (2008) Coordinated regulation of cell cycle transcripts by p53-inducible microRNAs, miR-192 and miR-215. Cancer Res 68(24):10105–10112PubMedCrossRefGoogle Scholar
  144. 144.
    Feng Z et al (2011) Tumor suppressor p53 meets microRNAs. J Mol Cell Biol 3(1):44–50PubMedCrossRefGoogle Scholar
  145. 145.
    Levine AJ (1997) p53, the cellular gatekeeper for growth and division. Cell 88(3):323–331PubMedCrossRefGoogle Scholar
  146. 146.
    Carr-Wilkinson J et al (2010) High frequency of p53/MDM2/p14ARF pathway abnormalities in relapsed neuroblastoma. Clin Cancer Res 16(4):1108–1118PubMedCrossRefGoogle Scholar
  147. 147.
    Momand J et al (1992) The mdm-2 oncogene product forms a complex with the p53 protein and inhibits p53-mediated transactivation. Cell 69(7):1237–1245PubMedCrossRefGoogle Scholar
  148. 148.
    Slack A, Shohet JM (2005) MDM2 as a critical effector of the MYCN oncogene in tumorigenesis. Cell Cycle 4(7):857–860PubMedCrossRefGoogle Scholar
  149. 149.
    Alaminos M et al (2004) Clustering of gene hypermethylation associated with clinical risk groups in neuroblastoma. J Natl Cancer Inst 96(16):1208–1219PubMedCrossRefGoogle Scholar
  150. 150.
    Astuti D et al (2001) RASSF1A promoter region CpG island hypermethylation in phaeochromocytomas and neuroblastoma tumours. Oncogene 20(51):7573–7577PubMedCrossRefGoogle Scholar
  151. 151.
    Banelli B et al (2002) Expression and methylation of CASP8 in neuroblastoma: identification of a promoter region. Nat Med 8(12):1333–1335 (author reply 1335)Google Scholar
  152. 152.
    Yang Q et al (2007) Methylation of CASP8, DCR2, and HIN-1 in neuroblastoma is associated with poor outcome. Clin Cancer Res 13(11):3191–3197PubMedCrossRefGoogle Scholar
  153. 153.
    van Noesel MM et al (2003) Clustering of hypermethylated genes in neuroblastoma. Genes Chromosomes Cancer 38(3):226–233PubMedCrossRefGoogle Scholar
  154. 154.
    Decock A et al (2011) Neuroblastoma epigenetics: from candidate gene approaches to genome-wide screenings. Epigenetics 6(8):962–970PubMedCrossRefGoogle Scholar
  155. 155.
    Grau E et al (2011) Hypermethylation of apoptotic genes as independent prognostic factor in neuroblastoma disease. Mol Carcinog 50(3):153–162PubMedCrossRefGoogle Scholar
  156. 156.
    Michalowski MB et al (2008) Methylation of tumor-suppressor genes in neuroblastoma: the RASSF1A gene is almost always methylated in primary tumors. Pediatr Blood Cancer 50(1):29–32PubMedCrossRefGoogle Scholar
  157. 157.
    Yagyu S et al (2008) Circulating methylated-DCR2 gene in serum as an indicator of prognosis and therapeutic efficacy in patients with MYCN nonamplified neuroblastoma. Clin Cancer Res 14(21):7011–7019PubMedCrossRefGoogle Scholar
  158. 158.
    Das S et al (2010) MicroRNA mediates DNA demethylation events triggered by retinoic acid during neuroblastoma cell differentiation. Cancer Res 70(20):7874–7881PubMedCrossRefGoogle Scholar
  159. 159.
    Kunej T et al (2011) Epigenetic regulation of microRNAs in cancer: an integrated review of literature. Mutat Res 717(1–2):77–84PubMedGoogle Scholar
  160. 160.
    Das S et al (2012) Modulation of neuroblastoma disease pathogenesis by an extensive network of epigenetically regulated microRNAs. OncogeneGoogle Scholar
  161. 161.
    Michlewski G et al (2008) Posttranscriptional regulation of miRNAs harboring conserved terminal loops. Mol Cell 32(3):383–393PubMedCrossRefGoogle Scholar
  162. 162.
    Moss EG, Lee RC, Ambros V (1997) The cold shock domain protein LIN-28 controls developmental timing in C. elegans and is regulated by the lin-4 RNA. Cell 88(5):637–646PubMedCrossRefGoogle Scholar
  163. 163.
    Boyerinas B et al (2008) Identification of let-7-regulated oncofetal genes. Cancer Res 68(8):2587–2591PubMedCrossRefGoogle Scholar
  164. 164.
    Rybak A et al (2008) A feedback loop comprising lin-28 and let-7 controls pre-let-7 maturation during neural stem-cell commitment. Nat Cell Biol 10(8):987–993PubMedCrossRefGoogle Scholar
  165. 165.
    Richards M et al (2004) The transcriptome profile of human embryonic stem cells as defined by SAGE. Stem Cells 22(1):51–64PubMedCrossRefGoogle Scholar
  166. 166.
    Viswanathan SR, Daley GQ, Gregory RI (2008) Selective blockade of microRNA processing by Lin28. Science 320(5872):97–100PubMedCrossRefGoogle Scholar
  167. 167.
    Newman MA, Thomson JM, Hammond SM (2008) Lin-28 interaction with the Let-7 precursor loop mediates regulated microRNA processing. RNA 14(8):1539–1549PubMedCrossRefGoogle Scholar
  168. 168.
    Piskounova E et al (2011) Lin28A and Lin28B inhibit let-7 microRNA biogenesis by distinct mechanisms. Cell 147(5):1066–1079PubMedCrossRefGoogle Scholar
  169. 169.
    Heo I et al (2009) TUT4 in concert with Lin28 suppresses microRNA biogenesis through pre-microRNA uridylation. Cell 138(4):696–708PubMedCrossRefGoogle Scholar
  170. 170.
    Lehrbach NJ et al (2009) LIN-28 and the poly(U) polymerase PUP-2 regulate let-7 microRNA processing in Caenorhabditis elegans. Nat Struct Mol Biol 16(10):1016–1020PubMedCrossRefGoogle Scholar
  171. 171.
    Hagan JP, Piskounova E, Gregory RI (2009) Lin28 recruits the TUTase Zcchc11 to inhibit let-7 maturation in mouse embryonic stem cells. Nat Struct Mol Biol 16(10):1021–1025PubMedCrossRefGoogle Scholar
  172. 172.
    Yu J et al (2007) Induced pluripotent stem cell lines derived from human somatic cells. Science 318(5858):1917–1920PubMedCrossRefGoogle Scholar
  173. 173.
    Viswanathan SR et al (2009) Lin28 promotes transformation and is associated with advanced human malignancies. Nat Genet 41(7):843–848PubMedCrossRefGoogle Scholar
  174. 174.
    Iliopoulos D, Hirsch HA, Struhl K (2009) An epigenetic switch involving NF-kappaB, Lin28, Let-7 MicroRNA, and IL6 links inflammation to cell transformation. Cell 139(4):693–706PubMedCrossRefGoogle Scholar
  175. 175.
    King CE et al (2011) LIN28B promotes colon cancer progression and metastasis. Cancer Res 71(12):4260–4268PubMedCrossRefGoogle Scholar
  176. 176.
    Bejerano G et al (2004) Ultraconserved elements in the human genome. Science 304(5675):1321–1325PubMedCrossRefGoogle Scholar
  177. 177.
    Calin GA et al (2007) Ultraconserved regions encoding ncRNAs are altered in human leukemias and carcinomas. Cancer Cell 12(3):215–229PubMedCrossRefGoogle Scholar
  178. 178.
    Mestdagh P et al (2010) An integrative genomics screen uncovers ncRNA T-UCR functions in neuroblastoma tumours. Oncogene 29(24):3583–3592PubMedCrossRefGoogle Scholar
  179. 179.
    Scaruffi P et al (2009) Transcribed-ultra conserved region expression is associated with outcome in high-risk neuroblastoma. BMC Cancer 9:441PubMedCrossRefGoogle Scholar
  180. 180.
    Yu M et al (2009) High expression of ncRAN, a novel non-coding RNA mapped to chromosome 17q25.1, is associated with poor prognosis in neuroblastoma. Int J Oncol 34(4):931–938PubMedGoogle Scholar
  181. 181.
    Voth H et al (2007) Identification of DEIN, a novel gene with high expression levels in stage IVS neuroblastoma. Mol Cancer Res 5(12):1276–1284PubMedCrossRefGoogle Scholar
  182. 182.
    Chooniedass-Kothari S et al (2004) The steroid receptor RNA activator is the first functional RNA encoding a protein. FEBS Lett 566(1–3):43–47PubMedCrossRefGoogle Scholar
  183. 183.
    Candeias MM et al (2008) P53 mRNA controls p53 activity by managing Mdm2 functions. Nat Cell Biol 10(9):1098–1105PubMedCrossRefGoogle Scholar
  184. 184.
    Gupta RA et al (2010) Long non-coding RNA HOTAIR reprograms chromatin state to promote cancer metastasis. Nature 464(7291):1071–1076PubMedCrossRefGoogle Scholar
  185. 185.
    Rinn JL et al (2007) Functional demarcation of active and silent chromatin domains in human HOX loci by noncoding RNAs. Cell 129(7):1311–1323PubMedCrossRefGoogle Scholar
  186. 186.
    Abel F et al (2004) Mutations in the N-terminal domain of DFF45 in a primary germ cell tumor and in neuroblastoma tumors. Int J Oncol 25(5):1297–1302PubMedGoogle Scholar
  187. 187.
    le Nguyen B et al (2011) Phenotype restricted genome-wide association study using a gene-centric approach identifies three low-risk neuroblastoma susceptibility loci. PLoS Genet 7(3):e1002026CrossRefGoogle Scholar
  188. 188.
    Duijkers FA et al (2012) High anaplastic lymphoma kinase immunohistochemical staining in neuroblastoma and ganglioneuroblastoma is an independent predictor of poor outcome. Am J Pathol 180(3):1223–1231PubMedCrossRefGoogle Scholar
  189. 189.
    Bourdeaut F et al (2012) ALK germline mutations in patients with neuroblastoma: a rare and weakly penetrant syndrome. Eur J Hum Genet 20(3):291–297PubMedCrossRefGoogle Scholar
  190. 190.
    de Pontual L et al (2011) Germline gain-of-function mutations of ALK disrupt central nervous system development. Hum Mutat 32(3):272–276PubMedCrossRefGoogle Scholar
  191. 191.
    Devoto M et al (2011) Genome-wide linkage analysis to identify genetic modifiers of ALK mutation penetrance in familial neuroblastoma. Hum Hered 71(2):135–139PubMedCrossRefGoogle Scholar
  192. 192.
    Passoni L et al (2009) Mutation-independent anaplastic lymphoma kinase overexpression in poor prognosis neuroblastoma patients. Cancer Res 69(18):7338–7346PubMedCrossRefGoogle Scholar
  193. 193.
    Caren H et al (2008) High incidence of DNA mutations and gene amplifications of the ALK gene in advanced sporadic neuroblastoma tumours. Biochem J 416(2):153–159PubMedCrossRefGoogle Scholar
  194. 194.
    Janoueix-Lerosey I et al (2008) Somatic and germline activating mutations of the ALK kinase receptor in neuroblastoma. Nature 455(7215):967–970PubMedCrossRefGoogle Scholar
  195. 195.
    George RE et al (2007) Genome-wide analysis of neuroblastomas using high-density single nucleotide polymorphism arrays. PLoS One 2(2):e255PubMedCrossRefGoogle Scholar
  196. 196.
    Schulte JH et al (2011) High ALK receptor tyrosine kinase expression supersedes ALK mutation as a determining factor of an unfavorable phenotype in primary neuroblastoma. Clin Cancer Res 17(15):5082–5092PubMedCrossRefGoogle Scholar
  197. 197.
    Shukla N et al (2012) Oncogene mutation profiling of pediatric solid tumors reveals significant subsets of embryonal rhabdomyosarcoma and neuroblastoma with mutated genes in growth signaling pathways. Clin Cancer Res 18(3):748–757PubMedCrossRefGoogle Scholar
  198. 198.
    Perri P et al (2005) PHOX2B mutations and genetic predisposition to neuroblastoma. Oncogene 24(18):3050–3053PubMedCrossRefGoogle Scholar
  199. 199.
    Bourdeaut F et al (2005) Germline mutations of the paired-like homeobox 2B (PHOX2B) gene in neuroblastoma. Cancer Lett 228(1–2):51–58PubMedCrossRefGoogle Scholar
  200. 200.
    McConville C et al (2006) PHOX2B analysis in non-syndromic neuroblastoma cases shows novel mutations and genotype-phenotype associations. Am J Med Genet A 140(12):1297–1301PubMedGoogle Scholar
  201. 201.
    Ghiorzo P et al (2006) Impact of E27X, a novel CDKN2A germ line mutation, on p16 and p14ARF expression in Italian melanoma families displaying pancreatic cancer and neuroblastoma. Hum Mol Genet 15(18):2682–2689PubMedCrossRefGoogle Scholar
  202. 202.
    Obana K et al (2003) Aberrations of p16INK4A, p14ARF and p15INK4B genes in pediatric solid tumors. Int J Oncol 23(4):1151–1157PubMedGoogle Scholar
  203. 203.
    Caren H et al (2008) High-resolution array copy number analyses for detection of deletion, gain, amplification and copy-neutral LOH in primary neuroblastoma tumors: four cases of homozygous deletions of the CDKN2A gene. BMC Genomics 9:353PubMedCrossRefGoogle Scholar
  204. 204.
    Omura-Minamisawa M et al (2001) p16/p14(ARF) cell cycle regulatory pathways in primary neuroblastoma: p16 expression is associated with advanced stage disease. Clin Cancer Res 7(11):3481–3490PubMedGoogle Scholar
  205. 205.
    Molenaar JJ et al (2003) Rearrangements and increased expression of cyclin D1 (CCND1) in neuroblastoma. Genes Chromosomes Cancer 36(3):242–249PubMedCrossRefGoogle Scholar
  206. 206.
    Martinelli S et al (2006) Activating PTPN11 mutations play a minor role in pediatric and adult solid tumors. Cancer Genet Cytogenet 166(2):124–129PubMedCrossRefGoogle Scholar
  207. 207.
    Mutesa L et al (2008) Germline PTPN11 missense mutation in a case of Noonan syndrome associated with mediastinal and retroperitoneal neuroblastic tumors. Cancer Genet Cytogenet 182(1):40–42PubMedCrossRefGoogle Scholar
  208. 208.
    Origone P et al (2003) Homozygous inactivation of NF1 gene in a patient with familial NF1 and disseminated neuroblastoma. Am J Med Genet A 118A(4):309–313PubMedCrossRefGoogle Scholar
  209. 209.
    Kong XT et al (1997) Expression and mutational analysis of the DCC, DPC4, and MADR2/JV18-1 genes in neuroblastoma. Cancer Res 57(17):3772–3778PubMedGoogle Scholar
  210. 210.
    Foley NH et al (2010) MicroRNA-184 inhibits neuroblastoma cell survival through targeting the serine/threonine kinase AKT2. Mol Cancer 9:83PubMedCrossRefGoogle Scholar
  211. 211.
    Le MT et al (2009) MicroRNA-125b is a novel negative regulator of p53. Genes Dev 23(7):862–876PubMedCrossRefGoogle Scholar
  212. 212.
    Evangelisti C et al (2009) MiR-128 up-regulation inhibits Reelin and DCX expression and reduces neuroblastoma cell motility and invasiveness. FASEB J 23(12):4276–4287PubMedCrossRefGoogle Scholar
  213. 213.
    Lin RJ, Lin YC, Yu AL (2010) miR-149* induces apoptosis by inhibiting Akt1 and E2F1 in human cancer cells. Mol Carcinog 49(8):719–727PubMedGoogle Scholar
  214. 214.
    Chen H et al (2010) miR-7 and miR-214 are specifically expressed during neuroblastoma differentiation, cortical development and embryonic stem cells differentiation, and control neurite outgrowth in vitro. Biochem Biophys Res Commun 394(4):921–927PubMedCrossRefGoogle Scholar
  215. 215.
    Meseguer S et al (2011) MicroRNAs-10a and -10b contribute to retinoic acid-induced differentiation of neuroblastoma cells and target the alternative splicing regulatory factor SFRS1 (SF2/ASF). J Biol Chem 286(6):4150–4164PubMedCrossRefGoogle Scholar
  216. 216.
    Haug BH et al (2011) MYCN-regulated miRNA-92 inhibits secretion of the tumor suppressor DICKKOPF-3 (DKK3) in neuroblastoma. Carcinogenesis 32(7):1005–1012PubMedCrossRefGoogle Scholar
  217. 217.
    Huang TC et al (2011) Silencing of miR-124 induces neuroblastoma SK-N-SH cell differentiation, cell cycle arrest and apoptosis through promoting AHR. FEBS Lett 585(22):3582–3586PubMedCrossRefGoogle Scholar
  218. 218.
    Makeyev EV et al (2007) The microRNA miR-124 promotes neuronal differentiation by triggering brain-specific alternative pre-mRNA splicing. Mol Cell 27(3):435–448PubMedCrossRefGoogle Scholar
  219. 219.
    Lee JJ et al (2012) MiR-27b targets PPARgamma to inhibit growth, tumor progression and the inflammatory response in neuroblastoma cells. Oncogene 31(33):3818–3825PubMedCrossRefGoogle Scholar
  220. 220.
    Xu H et al (2009) MicroRNA miR-29 modulates expression of immunoinhibitory molecule B7–H3: potential implications for immune based therapy of human solid tumors. Cancer Res 69(15):6275–6281PubMedCrossRefGoogle Scholar
  221. 221.
    Annibali D et al (2012) A new module in neural differentiation control: two microRNAs upregulated by retinoic acid, miR-9 and -103, target the differentiation inhibitor ID2. PLoS One 7(7):e40269PubMedCrossRefGoogle Scholar
  222. 222.
    Zhang H et al (2012) MicroRNA-9 targets matrix metalloproteinase 14 to inhibit invasion, metastasis, and angiogenesis of neuroblastoma cells. Mol Cancer Ther 11(7):1454–1466PubMedCrossRefGoogle Scholar
  223. 223.
    Moncini S et al (2011) The role of miR-103 and miR-107 in regulation of CDK5R1 expression and in cellular migration. PLoS ONE 6(5):e20038PubMedCrossRefGoogle Scholar
  224. 224.
    Afanasyeva EA et al (2011) MicroRNA miR-885-5p targets CDK2 and MCM5, activates p53 and inhibits proliferation and survival. Cell Death Differ 18(6):974–984PubMedCrossRefGoogle Scholar
  225. 225.
    Beveridge NJ et al (2009) Down-regulation of miR-17 family expression in response to retinoic acid induced neuronal differentiation. Cell Signal 21(12):1837–1845PubMedCrossRefGoogle Scholar
  226. 226.
    Loven J et al (2010) MYCN-regulated microRNAs repress estrogen receptor-alpha (ESR1) expression and neuronal differentiation in human neuroblastoma. Proc Natl Acad Sci USA 107(4):1553–1558PubMedCrossRefGoogle Scholar
  227. 227.
    Chayka O et al (2009) Clusterin, a haploinsufficient tumor suppressor gene in neuroblastomas. J Natl Cancer Inst 101(9):663–677PubMedCrossRefGoogle Scholar

Copyright information

© Springer-Verlag Berlin Heidelberg 2012

Authors and Affiliations

  • Raquel Domingo-Fernandez
    • 1
    • 2
  • Karen Watters
    • 1
    • 2
  • Olga Piskareva
    • 1
    • 2
  • Raymond L. Stallings
    • 1
    • 2
    Email author
  • Isabella Bray
    • 1
    • 2
  1. 1.Department of Cancer GeneticsRoyal College of Surgeons in IrelandDublinIreland
  2. 2.Children’s Research CentreOur Lady’s Children’s HospitalDublinIreland

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