Hepatoblastoma: New Insights into the Biology of Embryonal Tumors of the Liver

  • Dolores López-TerradaEmail author
Part of the Molecular and Translational Medicine book series (MOLEMED)


Malignant tumors of the liver are rare in children, with an approximate incidence of 1.8 cases per million, representing 1 % of all malignancies diagnosed during childhood. Hepatocellular neoplasms are the most common type of primary tumors of the liver in children, with hepatoblastoma (HB) being the most common during the first years of life (median age of diagnosis is 1 year), followed by hepatocellular carcinoma, usually affecting older children and adolescents (Hepatology 38:560–566, 2003; Hum Pathol 14:512–537, 1983). Several sources have reported an increase in the incidence of HB during the last two decades, both in the United States and in Japan, as well as a significantly higher rate of HB among low and very low birth weight infants. Primary liver tumors account for 6–8 % of all congenital tumors. HB has been associated with a number of constitutional genetic abnormalities, malformations, familial cancer syndromes (familial adenomatous polyposis, Beckwith–Wiedemann syndrome), and metabolic disorders (Glycogen storage diseases types I and IV) (Liver Disease in Children, 2007). However, most HBs are sporadic and the etiology for these tumors is not presently known.


Hepatoblastoma Biology Signaling pathways Wnt Hepatic stem cell 



The author would like to sincerely thank Kayuri Patel and Karen Prince for their valuable assistance in the creation of the figures and editing of this chapter.


  1. 1.
    Darbari A, Sabin KM, Shapiro CN, et al. Epidemiology of primary hepatic malignancies in U.S. children. Hepatology. 2003;38:560–6.PubMedGoogle Scholar
  2. 2.
    Weinberg AG, Finegold MJ. Primary hepatic tumors of childhood. Hum Pathol. 1983; 14:512–37.PubMedGoogle Scholar
  3. 3.
    Lopez-Terrada D, Finegold MJ. Tumors of the liver. In: Suchy FJ, editor. Liver disease in children. New York: Cambridge University Press; 2007. p. 943–75.Google Scholar
  4. 4.
    Finegold MJ. Tumors of the liver. Semin Liver Dis. 1994;14:270–81.PubMedGoogle Scholar
  5. 5.
    von Schweinitz D, Byrd DJ, Hecker H, et al. Efficiency and toxicity of ifosfamide, cisplatin and doxorubicin in the treatment of childhood hepatoblastoma. Study Committee of the Cooperative Paediatric Liver Tumour Study HB89 of the German Society for Paediatric Oncology and Haematology. Eur J Cancer. 1997;33:1243–9.Google Scholar
  6. 6.
    Katzenstein HM, London WB, Douglass EC, et al. Treatment of unresectable and metastatic hepatoblastoma: a pediatric oncology group phase II study. J Clin Oncol. 2002;20:3438–44.PubMedGoogle Scholar
  7. 7.
    Fuchs J, Rydzynski J, Von Schweinitz D, et al. Pretreatment prognostic factors and treatment results in children with hepatoblastoma: a report from the German Cooperative Pediatric Liver Tumor Study HB 94. Cancer. 2002;95:172–82.PubMedGoogle Scholar
  8. 8.
    Jung SE, Kim KH, Kim MY, et al. Clinical characteristics and prognosis of patients with hepatoblastoma. World J Surg. 2001;25:126–30.PubMedGoogle Scholar
  9. 9.
    Perilongo G, Shafford E, Plaschkes J. SIOPEL trials using preoperative chemotherapy in hepatoblastoma. Lancet Oncol. 2000;1:94–100.PubMedGoogle Scholar
  10. 10.
    Malogolowkin MH, Katzenstein HM, Krailo M, et al. Complete surgical resection is curative for children with hepatoblastoma with pure fetal histology: a report from the Children’s Oncology Group. J Clin Oncol. 2011;29(24):3301-6.Google Scholar
  11. 11.
    Haas JE, Muczynski KA, Krailo M, et al. Histopathology and prognosis in childhood hepatoblastoma and hepatocarcinoma. Cancer. 1989;64:1082–95.PubMedGoogle Scholar
  12. 12.
    Haas JE, Feusner JH, Finegold MJ. Small cell undifferentiated histology in hepatoblastoma may be unfavorable. Cancer. 2001;92:3130–4.PubMedGoogle Scholar
  13. 13.
    Schneider NR, Cooley LD, Finegold MJ, et al. The first recurring chromosome translocation in hepatoblastoma: der(4)t(1;4)(q12;q34). Genes Chromosomes Cancer. 1997;19:291–4.PubMedGoogle Scholar
  14. 14.
    Yeh YA, Rao PH, Cigna CT, et al. Trisomy 1q, 2, and 20 in a case of hepatoblastoma: possible significance of 2q35-q37 and 1q12-q21 rearrangements. Cancer Genet Cytogenet. 2000; 123:140–3.PubMedGoogle Scholar
  15. 15.
    Tomlinson GE, Douglass EC, Pollock BH, et al. Cytogenetic evaluation of a large series of hepatoblastomas: numerical abnormalities with recurring aberrations involving 1q12-q21. Genes Chromosomes Cancer. 2005;44:177–84.PubMedGoogle Scholar
  16. 16.
    Adesina AM, Nguyen Y, Guanaratne P, et al. FOXG1 is overexpressed in hepatoblastoma. Hum Pathol. 2007;38:400–9.PubMedGoogle Scholar
  17. 17.
    Suzuki M, Kato M, Yuyan C, et al. Whole-genome profiling of chromosomal aberrations in hepatoblastoma using high-density single-nucleotide polymorphism genotyping microarrays. Cancer Sci. 2008;99:564–70.PubMedGoogle Scholar
  18. 18.
    Cairo S, Armengol C, De Reynies A, et al. Hepatic stem-like phenotype and interplay of Wnt/beta-catenin and Myc signaling in aggressive childhood liver cancer. Cancer Cell. 2008;14:471–84.PubMedGoogle Scholar
  19. 19.
    Sainati L, Leszl A, Stella M, et al. Cytogenetic analysis of hepatoblastoma: hypothesis of cytogenetic evolution in such tumors and results of a multicentric study. Cancer Genet Cytogenet. 1998;104:39–44.PubMedGoogle Scholar
  20. 20.
    Gray SG, Hartmann W, Eriksson T, et al. Expression of genes involved with cell cycle control, cell growth and chromatin modification are altered in hepatoblastomas. Int J Mol Med. 2000;6:161–9.PubMedGoogle Scholar
  21. 21.
    Weber RG, Pietsch T, von Schweinitz D, et al. Characterization of genomic alterations in hepatoblastomas. A role for gains on chromosomes 8q and 20 as predictors of poor outcome. Am J Pathol. 2000;157:571–8.PubMedGoogle Scholar
  22. 22.
    Maris JM, Denny CT. Focus on embryonal malignancies. Cancer Cell. 2002;2:447–50.PubMedGoogle Scholar
  23. 23.
    Nusse R. Wnt signaling in disease and in development. Cell Res. 2005;15:28–32.PubMedGoogle Scholar
  24. 24.
    Reguart N, He B, Taron M, et al. The role of Wnt signaling in cancer and stem cells. Future Oncol. 2005;1:787–97.PubMedGoogle Scholar
  25. 25.
    Calvisi DF, Conner EA, Ladu S, et al. Activation of the canonical Wnt/beta-catenin pathway confers growth advantages in c-Myc/E2F1 transgenic mouse model of liver cancer. J Hepatol. 2005;42:842–9.PubMedGoogle Scholar
  26. 26.
    Thompson MD, Monga SP. WNT/beta-catenin signaling in liver health and disease. Hepatology. 2007;45:1298–305.PubMedGoogle Scholar
  27. 27.
    Fodde R, Brabletz T. Wnt/beta-catenin signaling in cancer stemness and malignant behavior. Curr Opin Cell Biol. 2007;19:150–8.PubMedGoogle Scholar
  28. 28.
    Koesters R, von Knebel Doeberitz M. The Wnt signaling pathway in solid childhood tumors. Cancer Lett. 2003;198:123–38.PubMedGoogle Scholar
  29. 29.
    Morin PJ, Sparks AB, Korinek V, et al. Activation of beta-catenin-Tcf signaling in colon cancer by mutations in beta-catenin or APC. Science. 1997;275:1787–90.PubMedGoogle Scholar
  30. 30.
    Rimm DL, Caca K, Hu G, et al. Frequent nuclear/cytoplasmic localization of beta-catenin without exon 3 mutations in malignant melanoma. Am J Pathol. 1999;154:325–9.PubMedGoogle Scholar
  31. 31.
    Palacios J, Gamallo C. Mutations in the beta-catenin gene (CTNNB1) in endometrioid ovarian carcinomas. Cancer Res. 1998;58:1344–7.PubMedGoogle Scholar
  32. 32.
    Coste A, Lefaucheur JP, Wang QP, et al. Expression of the transforming growth factor beta isoforms in inflammatory cells of nasal polyps. Arch Otolaryngol Head Neck Surg. 1998;124:1361–6.PubMedGoogle Scholar
  33. 33.
    Loeppen S, Koehle C, Buchmann A, et al. A beta-catenin-dependent pathway regulates expression of cytochrome P450 isoforms in mouse liver tumors. Carcinogenesis. 2005;26:239–48.PubMedGoogle Scholar
  34. 34.
    Zucman-Rossi J, Jeannot E, Nhieu JT, et al. Genotype-phenotype correlation in hepatocellular adenoma: new classification and relationship with HCC. Hepatology. 2006;43:515–24.PubMedGoogle Scholar
  35. 35.
    Buendia MA. Genetic alterations in hepatoblastoma and hepatocellular carcinoma: common and distinctive aspects. Med Pediatr Oncol. 2002;39:530–5.PubMedGoogle Scholar
  36. 36.
    Giardiello FM, Petersen GM, Brensinger JD, et al. Hepatoblastoma and APC gene mutation in familial adenomatous polyposis. Gut. 1996;39:867–9.PubMedGoogle Scholar
  37. 37.
    Kinzler KW, Vogelstein B. Lessons from hereditary colorectal cancer. Cell. 1996;87:159–70.PubMedGoogle Scholar
  38. 38.
    Kurahashi H, Takami K, Oue T, et al. Biallelic inactivation of the APC gene in hepatoblastoma. Cancer Res. 1995;55:5007–11.PubMedGoogle Scholar
  39. 39.
    Oda H, Imai Y, Nakatsuru Y, et al. Somatic mutations of the APC gene in sporadic hepatoblastomas. Cancer Res. 1996;56:3320–3.PubMedGoogle Scholar
  40. 40.
    Koch A, Denkhaus D, Albrecht S, et al. Childhood hepatoblastomas frequently carry a mutated degradation targeting box of the beta-catenin gene. Cancer Res. 1999;59:269–73.PubMedGoogle Scholar
  41. 41.
    Blaker H, Hofmann WJ, Rieker RJ, et al. Beta-catenin accumulation and mutation of the CTNNB1 gene in hepatoblastoma. Genes Chromosomes Cancer. 1999;25:399–402.PubMedGoogle Scholar
  42. 42.
    Wei Y, Fabre M, Branchereau S, et al. Activation of beta-catenin in epithelial and mesenchymal hepatoblastomas. Oncogene. 2000;19:498–504.PubMedGoogle Scholar
  43. 43.
    Jeng YM, Wu MZ, Mao TL, et al. Somatic mutations of beta-catenin play a crucial role in the tumorigenesis of sporadic hepatoblastoma. Cancer Lett. 2000;152:45–51.PubMedGoogle Scholar
  44. 44.
    Park WS, Oh RR, Park JY, et al. Nuclear localization of beta-catenin is an important prognostic factor in hepatoblastoma. J Pathol. 2001;193:483–90.PubMedGoogle Scholar
  45. 45.
    Takayasu H, Horie H, Hiyama E, et al. Frequent deletions and mutations of the beta-catenin gene are associated with overexpression of cyclin D1 and fibronectin and poorly differentiated histology in childhood hepatoblastoma. Clin Cancer Res. 2001;7:901–8.PubMedGoogle Scholar
  46. 46.
    Taniguchi K, Roberts LR, Aderca IN, et al. Mutational spectrum of beta-catenin, AXIN1, and AXIN2 in hepatocellular carcinomas and hepatoblastomas. Oncogene. 2002;21:4863–71.PubMedGoogle Scholar
  47. 47.
    Armengol C, Cairo S, Fabre M, et al. Wnt signaling and hepatocarcinogenesis: the hepatoblastoma model. Int J Biochem Cell Biol. 2008;43:265–70.Google Scholar
  48. 48.
    Brown AL, Graham DE, Nissley SP, et al. Developmental regulation of insulin-like growth factor II mRNA in different rat tissues. J Biol Chem. 1986;261:13144–50.PubMedGoogle Scholar
  49. 49.
    Prawitt D, Enklaar T, Gartner-Rupprecht B, et al. Microdeletion and IGF2 loss of imprinting in a cascade causing Beckwith-Wiedemann syndrome with Wilms’ tumor. Nat Genet. 2005;37:785–6. Author reply 786–7.PubMedGoogle Scholar
  50. 50.
    Tomizawa M, Saisho H. Signaling pathway of insulin-like growth factor-II as a target of molecular therapy for hepatoblastoma. World J Gastroenterol. 2006;12:6531–5.PubMedGoogle Scholar
  51. 51.
    Li X, Adam G, Cui H, et al. Expression, promoter usage and parental imprinting status of insulin-like growth factor II (IGF2) in human hepatoblastoma: uncoupling of IGF2 and H19 imprinting. Oncogene. 1995;11:221–9.PubMedGoogle Scholar
  52. 52.
    Hartmann W, Waha A, Koch A, et al. p57(KIP2) is not mutated in hepatoblastoma but shows increased transcriptional activity in a comparative analysis of the three imprinted genes p57(KIP2), IGF2, and H19. Am J Pathol. 2000;157:1393–403.PubMedGoogle Scholar
  53. 53.
    Eriksson T, Frisk T, Gray SG, et al. Methylation changes in the human IGF2 p3 promoter parallel IGF2 expression in the primary tumor, established cell line, and xenograft of a human hepatoblastoma. Exp Cell Res. 2001;270:88–95.PubMedGoogle Scholar
  54. 54.
    Luo JH, Ren B, Keryanov S, et al. Transcriptomic and genomic analysis of human hepatocellular carcinomas and hepatoblastomas. Hepatology. 2006;44:1012–24.PubMedGoogle Scholar
  55. 55.
    Lopez-Terrada D, Gunaratne PH, Adesina AM, et al. Histologic subtypes of hepatoblastoma are characterized by differential canonical Wnt and Notch pathway activation in DLK+ precursors. Hum Pathol. 2009;40:783–94.PubMedGoogle Scholar
  56. 56.
    Honda S, Arai Y, Haruta M, et al. Loss of imprinting of IGF2 correlates with hypermethylation of the H19 differentially methylated region in hepatoblastoma. Br J Cancer. 2008;99:1891–9.PubMedGoogle Scholar
  57. 57.
    Zatkova A, Rouillard JM, Hartmann W, et al. Amplification and overexpression of the IGF2 regulator PLAG1 in hepatoblastoma. Genes Chromosomes Cancer. 2004;39:126–37.PubMedGoogle Scholar
  58. 58.
    Vivanco I, Sawyers CL. The phosphatidylinositol 3-Kinase AKT pathway in human cancer. Nat Rev Cancer. 2002;2:489–501.PubMedGoogle Scholar
  59. 59.
    Hartmann W, Kuchler J, Koch A, et al. Activation of phosphatidylinositol-3′-kinase/AKT signaling is essential in hepatoblastoma survival. Clin Cancer Res. 2009;15:4538–45.PubMedGoogle Scholar
  60. 60.
    Adesina AM, Lopez-Terrada D, Wong KK, et al. Gene expression profiling reveals signatures characterizing histologic subtypes of hepatoblastoma and global deregulation in cell growth and survival pathways. Hum Pathol. 2009;40:843–53.PubMedGoogle Scholar
  61. 61.
    von Schweinitz D, Fuchs J, Gluer S, et al. The occurrence of liver growth factor in hepatoblastoma. Eur J Pediatr Surg. 1998;8:133–6.Google Scholar
  62. 62.
    Tan X, Apte U, Micsenyi A, et al. Epidermal growth factor receptor: a novel target of the Wnt/beta-catenin pathway in liver. Gastroenterology. 2005;129:285–302.PubMedGoogle Scholar
  63. 63.
    Ranganathan S, Tan X, Monga SP. Beta-Catenin and met deregulation in childhood Hepatoblastomas. Pediatr Dev Pathol. 2005;8:435–47.PubMedGoogle Scholar
  64. 64.
    Grotegut S, Kappler R, Tarimoradi S, et al. Hepatocyte growth factor protects hepatoblastoma cells from chemotherapy-induced apoptosis by AKT activation. Int J Oncol. 2010; 36:1261–7.PubMedGoogle Scholar
  65. 65.
    Huang S, He J, Zhang X, et al. Activation of the hedgehog pathway in human hepatocellular carcinomas. Carcinogenesis. 2006;27:1334–40.PubMedGoogle Scholar
  66. 66.
    Patil MA, Zhang J, Ho C, et al. Hedgehog signaling in human hepatocellular carcinoma. Cancer Biol Ther. 2006;5:111–7.PubMedGoogle Scholar
  67. 67.
    Oue T, Yoneda A, Uehara S, et al. Increased expression of the hedgehog signaling pathway in pediatric solid malignancies. J Pediatr Surg. 2010;45:387–92.PubMedGoogle Scholar
  68. 68.
    Eichenmuller M, Gruner I, Hagl B, et al. Blocking the hedgehog pathway inhibits hepatoblastoma growth. Hepatology. 2009;49:482–90.PubMedGoogle Scholar
  69. 69.
    Li YC, Deng YH, Guo ZH, et al. Prognostic value of hedgehog signal component expressions in hepatoblastoma patients. Eur J Med Res. 2010;15:468–74.PubMedGoogle Scholar
  70. 70.
    Galceran J, Sustmann C, Hsu SC, et al. LEF1-mediated regulation of Delta-like1 links Wnt and Notch signaling in somitogenesis. Genes Dev. 2004;18:2718–23.PubMedGoogle Scholar
  71. 71.
    Ayyanan A, Civenni G, Ciarloni L, et al. Increased Wnt signaling triggers oncogenic conversion of human breast epithelial cells by a Notch-dependent mechanism. Proc Natl Acad Sci U S A. 2006;103:3799–804.PubMedGoogle Scholar
  72. 72.
    Jensen CH, Jauho EI, Santoni-Rugiu E, et al. Transit-amplifying ductular (oval) cells and their hepatocytic progeny are characterized by a novel and distinctive expression of delta-like protein/preadipocyte factor 1/fetal antigen 1. Am J Pathol. 2004;164:1347–59.PubMedGoogle Scholar
  73. 73.
    Nagata T, Takahashi Y, Ishii Y, et al. Profiling of genes differentially expressed between fetal liver and postnatal liver using high-density oligonucleotide DNA array. Int J Mol Med. 2003; 11:713–21.PubMedGoogle Scholar
  74. 74.
    Yamada S, Ohira M, Horie H, et al. Expression profiling and differential screening between hepatoblastomas and the corresponding normal livers: identification of high expression of the PLK1 oncogene as a poor-prognostic indicator of hepatoblastomas. Oncogene. 2004;23:5901–11.PubMedGoogle Scholar
  75. 75.
    Cairo S, Wang Y, de Reynies A, et al. Stem cell-like micro-RNA signature driven by Myc in aggressive liver cancer. Proc Natl Acad Sci USA. 2010;107:20471–6.PubMedGoogle Scholar
  76. 76.
    Shafritz DA, Oertel M, Menthena A, et al. Liver stem cells and prospects for liver reconstitution by transplanted cells. Hepatology. 2006;43:S89–98.PubMedGoogle Scholar
  77. 77.
    Teufel A, Galle PR. Collecting evidence for a stem cell hypothesis in HCC. Gut. 2011; 59:870–1.Google Scholar
  78. 78.
    Kubota H, Reid LM. Clonogenic hepatoblasts, common precursors for hepatocytic and biliary lineages, are lacking classical major histocompatibility complex class I antigen. Proc Natl Acad Sci USA. 2000;97:12132–7.PubMedGoogle Scholar
  79. 79.
    Watanabe T, Nakagawa K, Ohata S, et al. SEK1/MKK4-mediated SAPK/JNK signaling participates in embryonic hepatoblast proliferation via a pathway different from NF-kappaB-induced anti-apoptosis. Dev Biol. 2002;250:332–47.PubMedGoogle Scholar
  80. 80.
    Tanimizu N, Nishikawa M, Saito H, et al. Isolation of hepatoblasts based on the expression of Dlk/Pref-1. J Cell Sci. 2003;116:1775–86.PubMedGoogle Scholar
  81. 81.
    Terris B, Cavard C, Perret C. EpCAM, a new marker for cancer stem cells in hepatocellular carcinoma. J Hepatol. 2010;52:280–1.PubMedGoogle Scholar
  82. 82.
    Wang X, Foster M, Al-Dhalimy M, et al. The origin and liver repopulating capacity of murine oval cells. Proc Natl Acad Sci U S A. 2003;100 Suppl 1:11881–8.PubMedGoogle Scholar
  83. 83.
    Chiba T, Kamiya A, Yokosuka O, et al. Cancer stem cells in hepatocellular carcinoma: recent progress and perspective. Cancer Lett. 2009;286:145–53.PubMedGoogle Scholar
  84. 84.
    Yang GH, Fan J, Xu Y, et al. Osteopontin combined with CD44, a novel prognostic biomarker for patients with hepatocellular carcinoma undergoing curative resection. Oncologist. 2008;13:1155–65.PubMedGoogle Scholar
  85. 85.
    Jin ZH, Yang RJ, Dong B, et al. Progenitor gene DLK1 might be an independent prognostic factor of liver cancer. Expert Opin Biol Ther. 2008;8:371–7.PubMedGoogle Scholar
  86. 86.
    Fiegel HC, Gluer S, Roth B, et al. Stem-like cells in human hepatoblastoma. J Histochem Cytochem. 2004;52:1495–501.PubMedGoogle Scholar
  87. 87.
    Koch A, Waha A, Hartmann W, et al. Elevated expression of Wnt antagonists is a common event in hepatoblastomas. Clin Cancer Res. 2005;11:4295–304.PubMedGoogle Scholar
  88. 88.
    Koch A, Weber N, Waha A, et al. Mutations and elevated transcriptional activity of conductin (AXIN2) in hepatoblastomas. J Pathol. 2004;204:546–54.PubMedGoogle Scholar
  89. 89.
    Udatsu Y, Kusafuka T, Kuroda S, et al. High frequency of beta-catenin mutations in hepatoblastoma. Pediatr Surg Int. 2001;17:508–12.PubMedGoogle Scholar
  90. 90.
    Pei Y, Kano J, Iijima T, et al. Overexpression of Dickkopf 3 in hepatoblastomas and hepatocellular carcinomas. Virchows Arch. 2009;454:639–46.PubMedGoogle Scholar
  91. 91.
    Wirths O, Waha A, Weggen S, et al. Overexpression of human Dickkopf-1, an antagonist of wingless/WNT signaling, in human hepatoblastomas and Wilms’ tumors. Lab Invest. 2003;83:429–34.PubMedGoogle Scholar
  92. 92.
    Miao J, Kusafuka T, Udatsu Y, et al. Sequence variants of the Axin gene in hepatoblastoma. Hepatol Res. 2003;25:174–9.PubMedGoogle Scholar
  93. 93.
    Aktas S, Zadeoglulari Z, Ercetin P, et al. The effect of differentiating and apoptotic agents on notch signalling pathway in hepatoblastoma. Hepatogastroenterology. 2010;57:891–8.PubMedGoogle Scholar
  94. 94.
    Dezso K, Halasz J, Bisgaard HC, et al. Delta-like protein (DLK) is a novel immunohistochemical marker for human hepatoblastomas. Virchows Arch. 2008;452:443–8.PubMedGoogle Scholar
  95. 95.
    Yoshida R, Ogata T, Masawa N, et al. Hepatoblastoma in a Noonan syndrome patient with a PTPN11 mutation. Pediatr Blood Cancer. 2008;50:1274–6.PubMedGoogle Scholar
  96. 96.
    von Schweinitz D, Faundez A, Teichmann B, et al. Hepatocyte growth-factor-scatter factor can stimulate post-operative tumor-cell proliferation in childhood hepatoblastoma. Int J Cancer. 2000;85:151–9.Google Scholar
  97. 97.
    von Horn H, Tally M, Hall K, et al. Expression levels of insulin-like growth factor binding proteins and insulin receptor isoforms in hepatoblastomas. Cancer Lett. 2001;162:253–60.Google Scholar
  98. 98.
    Gray SG, Eriksson T, Ekstrom C, et al. Altered expression of members of the IGF-axis in hepatoblastomas. Br J Cancer. 2000;82:1561–7.PubMedGoogle Scholar
  99. 99.
    Curia MC, Zuckermann M, De Lellis L, et al. Sporadic childhood hepatoblastomas show activation of beta-catenin, mismatch repair defects and p53 mutations. Mod Pathol. 2008;21:7–14.PubMedGoogle Scholar
  100. 100.
    Gray SG, Kytola S, Matsunaga T, et al. Comparative genomic hybridization reveals population-based genetic alterations in hepatoblastomas. Br J Cancer. 2000;83:1020–5.PubMedGoogle Scholar
  101. 101.
    Stejskalova E, Malis J, Snajdauf J, et al. Cytogenetic and array comparative genomic hybridization analysis of a series of hepatoblastomas. Cancer Genet Cytogenet. 2009;194:82–7.PubMedGoogle Scholar
  102. 102.
    Arai Y, Honda S, Haruta M, et al. Genome-wide analysis of allelic imbalances reveals 4q deletions as a poor prognostic factor and MDM4 amplification at 1q32.1 in hepatoblastoma. Genes Chromosomes Cancer. 2010;49:596–609.PubMedGoogle Scholar
  103. 103.
    Terracciano LM, Bernasconi B, Ruck P, et al. Comparative genomic hybridization analysis of hepatoblastoma reveals high frequency of X-chromosome gains and similarities between epithelial and stromal components. Hum Pathol. 2003;34:864–71.PubMedGoogle Scholar
  104. 104.
    Shin E, Lee KB, Park SY, et al. Gene expression profiling of human hepatoblastoma using archived formalin-fixed and paraffin-embedded tissues. Virchows Arch. 2011;458:453–65.PubMedGoogle Scholar
  105. 105.
    Thorgeirsson SS. The almighty MYC: orchestrating the micro-RNA universe to generate aggressive liver cancer. J Hepatol. 2011;55(2):486–7.PubMedGoogle Scholar
  106. 106.
    Magrelli A, Azzalin G, Salvatore M, et al. Altered microRNA expression patterns in hepatoblastoma patients. Transl Oncol. 2009;2:157–63.PubMedGoogle Scholar
  107. 107.
    von Frowein J, Pagel P, Kappler R, et al. MicroRNA-492 is processed from the keratin 19 gene and up-regulated in metastatic hepatoblastoma. Hepatology. 2011;53:833–42.Google Scholar

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© Springer Science+Business Media New York 2012

Authors and Affiliations

  1. 1.Department of PathologyTexas Children’s Hospital, Baylor College of MedicineHoustonUSA

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