Clinical and Translational Oncology

, Volume 12, Issue 9, pp 597–605 | Cite as

Candidate genes and potential targets for therapeutics in Wilms’ tumour

  • Christopher Blackmore
  • Max J. Coppes
  • Aru NarendranEmail author
Educational Series Molecular Targets in Oncology


Wilms’ tumour (WT) is the most common malignant renal tumour of childhood. During the past two decades or so, molecular studies carried out on biopsy specimens and tumour-derived cell lines have identified a multitude of chromosomal and epigenetic alterations in WT. In addition, a significant amount of evidence has been gathered to identify the genes and signalling pathways that play a defining role in its genesis, growth, survival and treatment responsiveness. As such, these molecules and mechanisms constitute potential targets for novel therapeutic strategies for refractory WT. In this report we aim to review some of the many candidate genes and intersecting pathways that underlie the complexities of WT biology.


Wilms’ tumour Genes Targets Therapeutics 


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  1. 1.
    Green DM, D’Angio GJ, Beckwith JB et al (1996) Wilms tumor. CA Cancer J Clin 46:46–63PubMedCrossRefGoogle Scholar
  2. 2.
    Davidoff AM (2009) Wilms’ tumor. Curr Opin Pediatr 21:357–364PubMedCrossRefGoogle Scholar
  3. 3.
    Ko EY, Ritchey ML (2009) Current management of Wilms’ tumor in children. J Pediatr Urol 5:56–65PubMedCrossRefGoogle Scholar
  4. 4.
    Sonn G, Shortliffe LM (2008) Management of Wilms tumor: current standard of care. Nat Clin Pract Urol 5:551–560PubMedCrossRefGoogle Scholar
  5. 5.
    Metzger ML, Dome JS (2005) Current therapy for Wilms’ tumor. Oncologist 10:815–826PubMedCrossRefGoogle Scholar
  6. 6.
    Mierau GW, Beckwith JB, Weeks DA (1987) Ultrastructure and histogenesis of the renal tumors of childhood: an overview. Ultrastruct Pathol 11:313–333PubMedCrossRefGoogle Scholar
  7. 7.
    Hastie ND (1994) The genetics of Wilms’ tumor: a case of disrupted development. Annu Rev Genet 28:523–558PubMedGoogle Scholar
  8. 8.
    Koesters R, Niggli F, von Knebel Doeberitz M, Stallmach T (2003) Nuclear accumulation of beta-catenin protein in Wilms’ tumours. J Pathol 199:68–76PubMedCrossRefGoogle Scholar
  9. 9.
    Li CM, Guo M, Borczuk A et al (2002) Gene expression in Wilms’ tumor mimics the earliest committed stage in the metanephric mesenchymalepithelial transition. Am J Pathol 160:2181–2190PubMedGoogle Scholar
  10. 10.
    Li W, Kessler P, Williams BR (2005) Transcript profiling of Wilms’ tumors reveals connections to kidney morphogenesis and expression patterns associated with anaplasia. Oncogene 24:457–468PubMedCrossRefGoogle Scholar
  11. 11.
    Brown KW, Malik KTA (2001) The molecular biology of Wilms’ tumour. Exp Rev Mol Med 14:1–16Google Scholar
  12. 12.
    Rigolet M, Faussillon M, Baudry D et al (2001) Profiling of differential gene expression in Wilms’ tumor by cDNA expression array. Pediatr Nephrol 16:1113–1121PubMedCrossRefGoogle Scholar
  13. 13.
    Breslow NE, Olson J, Moksness J et al (1996) Familial Wilms’ tumor: a descriptive study. Med Pediatr Oncol 27:398–403PubMedCrossRefGoogle Scholar
  14. 14.
    Breslow NE, Langholz B (1983) Childhood cancer incidence: geographical and temporal variations. Int J Cancer 32:703–716PubMedCrossRefGoogle Scholar
  15. 15.
    Matsunaga E (1981) Genetics of Wilms’ tumor. Hum Genet 57:231–246PubMedCrossRefGoogle Scholar
  16. 16.
    Miller RW, Fraumeni JF Jr, Manning MD (1964) Association of Wilms’ tumour with aniridia, hemihypertrophy and other congenital malformations. N Engl J Med 270:922–927PubMedCrossRefGoogle Scholar
  17. 17.
    Drash A, Sherman F, Hartmann WH, Blizzard RM (1970) A syndrome of pseudohermaphroditism, Wilms’ tumour, hypertension, and degenerative renal disease. J Pediatr 76:585–593PubMedCrossRefGoogle Scholar
  18. 18.
    Scott RH, Stiller CA, Walker L, Rahman N (2006) Syndromes and constitutional chromosomal abnormalities associated with Wilms tumor. J Med Genet 43:705–715PubMedCrossRefGoogle Scholar
  19. 19.
    Call KM, Glaser T, Ito CY et al (1990) Isolation and characterization of a zinc finger polypeptide gene at the human chromosome 11 Wilms’ tumor locus. Cell 60:509–520PubMedCrossRefGoogle Scholar
  20. 20.
    Huff V, Miwa H, Haber DA et al (1991) Evidence for WT1 as a Wilms’ tumor (WT) gene: intragenic germinal deletion in bilateral WT. Am J Hum Genet 48:997–1003PubMedGoogle Scholar
  21. 21.
    Gessler M, Konig A, Arden K et al (1994) Infrequent mutation of the WT1 gene in 77 Wilms’ tumors. Hum Mut 3:212–222PubMedCrossRefGoogle Scholar
  22. 22.
    Varanasi R, Bardeesy N, Ghahremani M et al (1994) Fine structure analysis of the WT1 gene is sporadic Wilms’ tumors. Proc Natl Acad Sci USA 91:3554–3558PubMedCrossRefGoogle Scholar
  23. 23.
    Huff V (1998) Wilms tumor genetics. Am J Hum Genet 79:260–267Google Scholar
  24. 24.
    Baudry D, Cabanis M-O, Fournet JC et al (2000) WT1 splicing alterations in Wilms’ tumor. Clin Cancer Res 10:3957–3965Google Scholar
  25. 25.
    Francke U (1979) Aniridia-Wilms’ tumor association: evidence for specific deletion of 11p13. Cytogenet Cell Genet 24:185–192PubMedCrossRefGoogle Scholar
  26. 26.
    Pelletier J, Bruening W, Kashtan CE et al (1991) Germline mutations in the Wilms’ tumor suppressor gene are associated with abnormal urogenital development in Denys-Drash syndrome. Cell 67:437–447PubMedCrossRefGoogle Scholar
  27. 27.
    Heathcott RW, Morison IM, Gubler MC et al (2002) A review of the phenotypic variation due to the Denys-Drash syndrome-associated germline WT1 mutation R362X. Hum Mutat 19:462PubMedCrossRefGoogle Scholar
  28. 28.
    Bruening W, Bardeesy N, Silverman BL et al (1992) Germline intronic and exonic mutations in the Wilms’ tumour gene (WT1) affecting urogenital development. Nat Genet 1:144–148PubMedCrossRefGoogle Scholar
  29. 29.
    Yang L, Han Y, Saurez Saiz F, Minden MD (2007) A tumor suppressor and oncogene: the WT1 story. Leukemia 21:868–876PubMedGoogle Scholar
  30. 30.
    Roberts SG (2005) Transcriptional regulation by WT1 in development. Curr Opin Genet Dev 15: 542–547PubMedCrossRefGoogle Scholar
  31. 31.
    Lee SB, Haber DA (2001) Wilms’ tumor and the WT1 gene. Exp Cell Res 264:74–99PubMedCrossRefGoogle Scholar
  32. 32.
    Rauscher FJ III, Morris JF, Tournay OE et al (1990) Binding of the Wilms’ tumor locus zinc finger protein to the EGR-1 consensus sequence. Science 250:1259–1262PubMedCrossRefGoogle Scholar
  33. 33.
    Morris JF, Madden SL, Tournay OE et al (1991) Characterization of the zinc finger protein to the EGR-1 consensus sequence. Oncogene 6:2339–2348PubMedGoogle Scholar
  34. 34.
    Hewitt SM, Hamada S, McDonnell TJ et al (1995) Regulation of the proto-oncogenes bcl-2 and cmyc by the Wilms’ tumor suppressor gene WT1. Cancer Res 55:5386–5389PubMedGoogle Scholar
  35. 35.
    Rupprecht HD, Drummond IA, Madden SL et al (1994) The Wilms’ tumor suppressor gene WT1 is negatively autoregulated. J Biol Chem 269:6198–6206PubMedGoogle Scholar
  36. 36.
    Ryan G, Steel-Perkins V, Morris JF et al (1995) Repression of Pax-2 by WT1 during normal kidney development. Development 121:867–875PubMedGoogle Scholar
  37. 37.
    Lee SB, Huang K, Palmer R et al (1999) The Wilms’ tumor suppressor WT1 encodes a transcriptional activator of amphiregulin. Cell 98:663–673PubMedCrossRefGoogle Scholar
  38. 38.
    Mayo MW, Wang CY, Drouin SS et al (1999) WT1 modulates apoptosis by transcriptionally upregulating the bcl-2 proto-oncogene. EMBO 18:3990–4003CrossRefGoogle Scholar
  39. 39.
    Wilhelm D, Englert C (2002) The Wilms’ tumor suppressor WT1 regulates early gonad development by activation of Sfl. Genes Dev 16:1839–1851PubMedCrossRefGoogle Scholar
  40. 40.
    Hosono S, Gross I, English MA et al (2000) Ecadherin is a WT1 target gene. J Biol Chem 275: 10943–10953PubMedCrossRefGoogle Scholar
  41. 41.
    Nurmemmedov E, Yengo RK, Ladomery MR, Thunnissen MM (2010) Kinetic behaviour of WT 1’s zinc finger domain in binding to the alpha-actinin-1 mRNA. Arch Biochem Biophys 497:21–27PubMedCrossRefGoogle Scholar
  42. 42.
    Valcarel J, Gebauer F (1997) Post-transcriptional regulation: the dawn of PTB. Curr Biol 7:R705–R708CrossRefGoogle Scholar
  43. 43.
    Niksic M, Slight J, Sanford JR et al (2003) The Wilms’ tumour protein (WT1) shuttles between nucleus and cytoplasm and is present in functional polysomes. Hum Mol Genet 13:463–471PubMedCrossRefGoogle Scholar
  44. 44.
    Kriedberg JA, Sariola H, Loring JM et al (1993) WT-1 is required for early kidney development. Cell 74:679–691CrossRefGoogle Scholar
  45. 45.
    Kreidberg J (2002) Kidneys and sex, the Wilms’ tumor connection. Pediatr Res 51:128PubMedCrossRefGoogle Scholar
  46. 46.
    Pritchard-Jones K (1999) The Wilms’ tumour gene, WT1 in normal and abnormal nephrogenesis. Pediatr Nephrol 13:620–625PubMedGoogle Scholar
  47. 47.
    Pohl M, Bhatnagar V, Mendoza SA, Nigam SK (1001) Toward an etiological classification of developmental disorders of the kidney and upper urinary tract. Kidney 61:10–19Google Scholar
  48. 48.
    Englert C, Hou X, Maheswaran S et al (1995) WT1 suppresses synthesis of the epidermal growth factor receptor and induces apoptosis. EMBO J 14:4662–4675PubMedGoogle Scholar
  49. 49.
    McMaster ML, Gessler M, Stanbridge EJ, Weissman BE (1995) WT1 expression alters tumorigenicity of the G401 kidney-derived cell line. Cell Growth Differ 6:1609–1617PubMedGoogle Scholar
  50. 50.
    Morrison DJ, English MA, Licht JD (2005) WT1 induces apoptosis through transcriptional regulation of the proapoptotic Bcl-2 family member Bak. Cancer Res 65:8174–8182PubMedCrossRefGoogle Scholar
  51. 51.
    Menke AL, Shvarts A, Riteco N et al (1997) Wilms’ tumor 1-KTS isoforms induce p53-independent apoptosis that can be partially rescued by expression of the epidermal growth factor receptor or the insulin receptor. Cancer Res 57:1353–1363PubMedGoogle Scholar
  52. 52.
    Hartkamp J, Carpenter B, Roberts SG (2010) The Wilms’ tumor suppressor protein WT1 is processed by the serine protease HtrA2/Omi. Mol Cell 37:159–171PubMedCrossRefGoogle Scholar
  53. 53.
    Cohen HT, Bossone SA, Zhu G et al (1997) Sp1 is a critical regulator of the Wilms’ tumor-1 gene. J Biol Chem 272:2901–2913PubMedCrossRefGoogle Scholar
  54. 54.
    Dehbi M, Pelletier J (1997) PAX8-mediated activation of the wt1 tumor suppressor gene. EMBO J 15:4297–4306Google Scholar
  55. 55.
    Dehbi M, Ghahremani M, Lechner M et al (1996) The paired-box transcription factor, PAX2, positively modulates expression of the Wilms’ tumor suppressor gene (WT1). Oncogene 13:447–453PubMedGoogle Scholar
  56. 56.
    Dehbi M, Hiscott J, Pelletier J (1998) Activation of the wt1 Wilms’ tumor suppressor gene by NFkappaB. Oncogene 16:2033–2039PubMedCrossRefGoogle Scholar
  57. 57.
    Bollig F, Perner B, Besenbeck B et al (2009) A highly conserved retinoic acid responsive element controls wt1a expression in the zebrafish pronephros. Development 136:2883–2892PubMedCrossRefGoogle Scholar
  58. 58.
    Sugiyama H (2010) WT1 (Wilms’ tumor gene 1): biology and cancer immunotherapy. Jpn J Clin Oncol 40:377–387PubMedCrossRefGoogle Scholar
  59. 59.
    Makki MS, Heinzel T, Englert C (2008) TSA downregulates Wilms tumor gene 1 (Wt1) expression at multiple levels. Nucleic Acids Res 36: 4067–4078PubMedCrossRefGoogle Scholar
  60. 60.
    Glienke W, Maute L, Koehl U et al (2007) Effective treatment of leukemic cell lines with wt1 siRNA. Leukemia 21:2164–2170PubMedCrossRefGoogle Scholar
  61. 61.
    Taipale J, Beachy P (2001) The Hedgehog and Wnt signalling pathways in cancer. Nature 411: 349–354PubMedCrossRefGoogle Scholar
  62. 62.
    Wodarz A, Nusse R (1998) Mechanisms of Wnt signaling in development. Annu Rev Cell Dev Biol 14:59–88PubMedCrossRefGoogle Scholar
  63. 63.
    Polakis P (2000) Wnt signaling and cancer. Genes Dev 14:1837–1851PubMedGoogle Scholar
  64. 64.
    Bienz M, Clevers H (2000) Linking colorectal cancer to Wnt signaling. Cell 17:3505–3511Google Scholar
  65. 65.
    Itoh K, Krupnik VE, Sokol SY (1998) Axis determination in Xenopus involves biochemical interactions of axin, glycogen synthase kinase 3 and ß-catenin. Curr Biol 8:591–594PubMedCrossRefGoogle Scholar
  66. 66.
    Schmidt-Ott KM, Barasch J (2003) WNT/beta-catenin signaling in nephron progenitors and their epithelial progeny. Kidney Int 74:1004–1008CrossRefGoogle Scholar
  67. 67.
    Giles RH, van Es JH, Clevers H (2003) Caught up in a Wnt storm: Wnt signaling in cancer. Biochim Biophys Acta 1653:1–24PubMedGoogle Scholar
  68. 68.
    Dallosso AR, Hancock AL, Szemes M et al (2009) Frequent long-range epigenetic silencing of protocadherin gene clusters on chromosome 5q31 in Wilms’ tumor. PLoS Genet 5:e1000745PubMedCrossRefGoogle Scholar
  69. 69.
    Behrens J, von Kries JP, Kuhl M et al (1996) Functional interaction of ß-catenin with the transcription factor LEF-1. Nature 382:638–642PubMedCrossRefGoogle Scholar
  70. 70.
    He TC, Sparks AB, Rago C et al (1998) Identification of c-MYC as a target of the APC pathway. Science 281:1509–1512PubMedCrossRefGoogle Scholar
  71. 71.
    Tetsu O, McCormick F (1999) ß-Catenin regulates expression of cyclin D1 in colon carcinoma cells. Nature 398:422–426PubMedCrossRefGoogle Scholar
  72. 72.
    Gumbiner BM (1995) Signal transduction of ß-catenin. Curr Opin Cell Biol 7:634–640PubMedCrossRefGoogle Scholar
  73. 73.
    Li C, Kim CE, Margolin AA et al (2004) CTNNB1 mutations and overexpression of Wnt/ß-catenin target genes in WT1-mutant Wilms’ tumors. Am J Pathol 165:1943–1953PubMedGoogle Scholar
  74. 74.
    Zirn B, Samans B, Wittman S et al (2006) Target genes of the WNT/ß-catenin pathway in Wilms tumors. Genes Chromosomes Cancer 45:565–574PubMedCrossRefGoogle Scholar
  75. 75.
    Corbin M, de Reyniès A, Rickman DS et al (2006) WNT/beta-catenin pathway activation in Wilms tumors: a unifying mechanism with multiple entries? Genes Chromosomes Cancer 48:816–827CrossRefGoogle Scholar
  76. 76.
    Wilmore HP, White GFJ, Howell RT, Brown KW (1994) Germline and somatic abnormalities of chromosome 7 in Wilms’ tumor. Cancer Genet Cytogenet 77:93–98PubMedCrossRefGoogle Scholar
  77. 77.
    Miozzo M, Perotti D, Minoletti F et al (1996) Mapping of a putative tumor suppressor locus to proximal 7p in Wilms tumors. Genomics 37:310–315PubMedCrossRefGoogle Scholar
  78. 78.
    Powlesland RM, Charles AK, Malik KT et al (2000) Loss of heterozygosity at 7p in Wilms’ tumour development. Br J Cancer 82:323–329PubMedCrossRefGoogle Scholar
  79. 79.
    Perotti D, Testi MA, Mondini P et al (2001). Refinement within single yeast artificial chromosome clones of a minimal region commonly deleted on the short arm of chromosome 7 in Wilms tumours. Gene Chromosome Cancer 31:42–47CrossRefGoogle Scholar
  80. 80.
    Vernon EG, Malik K, Reynolds P et al (2003) The parathyroid hormone-responsive B1 gene is interrupted by a t(1;7)(q42;p15) breakpoint associated with Wilms’ tumour. Oncogene 22:1371–1380PubMedCrossRefGoogle Scholar
  81. 81.
    Adams AE, Rosenblatt M, Suva LJ (1999) Identification of a novel parathyroid hormone-responsive gene in human osteoblastic cells. Bone 24:305–313PubMedCrossRefGoogle Scholar
  82. 82.
    de Kraker J, Voute PA (1979) Hypercalcemia and elevated parathyroid hormone levels in association with nephroblastoma. Helv Paediatr Acta 34:459–460PubMedGoogle Scholar
  83. 83.
    Ohshima J, Haruta M, Arai Y et al (2009) Two candidate tumor suppressor genes, MEOX2 and SOSTDC1, identified in a 7p21 homozygous deletion region in a Wilms tumor. Genes Chromosomes Cancer 48:1037–1050PubMedCrossRefGoogle Scholar
  84. 84.
    Perotti D, De Vecchi G, Testi MA et al (2004) Germline mutations of the POUF62 gene in Wilms’ tumors with loss of heterozygosity on chromosome 7p14. Hum Mutat 24:400–407PubMedCrossRefGoogle Scholar
  85. 85.
    Zhou H, Yoshioka T, Nathans J (1996) Retinaderived POU-domain factor-1: a complex POU-domain gene implicated in the development of retinal ganglion and amacrine cells. J Neurosci 16:2261–2274PubMedGoogle Scholar
  86. 86.
    Phillips K, Luisi B (2000) The virtuoso of versatility: POU proteins that flex to fit. J Mol Biol 302:1023–1039PubMedCrossRefGoogle Scholar
  87. 87.
    Anglesio MS, Evdokimova V, Melnyk N et al (2004) Differential expression of a novel ankyrin containing E3 ubiquitin-protein ligase, Hace1, in sporadic Wilms’ tumor versus normal kidney. Hum Mol Genet 13:2061–2074PubMedCrossRefGoogle Scholar
  88. 88.
    Bruce CK, Howard P, Nowak NJ, Hoban PR (2003) Molecular analysis of region in Wilms’ tumor. Cancer Genet 141:106–113CrossRefGoogle Scholar
  89. 89.
    Hoban PR, Cowen RL, Mitchell EL et al (1997) Physical localization of the breakpoints of a constitutional translocation t(5;6)(q21;q21) in a child with bilateral Wilms’ tumor. J Med Genet 34:343–345PubMedCrossRefGoogle Scholar
  90. 90.
    Solis V, Pritchard J, Cowell JK (1998) Cytogenetic changes in Wilms’ tumors. Cancer Genet 34:223–234CrossRefGoogle Scholar
  91. 91.
    Utada Y, Haga S, Kajiwara T et al (2000) Mapping of target regions or allelic loss in primary breast cancers to 1-cM intervals on genomic contigs at 6q21 and 6q25.3. Jpn J Cancer Res 91:293–300PubMedGoogle Scholar
  92. 92.
    Zhang Y, Matthiesen P, Harder S et al (2000) A 3-cM commonly deleted region on 6q21 in leukemias and lymphomas delineated by fluorescence in situ hybridization. Genes Chromosomes Cancer 27:52–58PubMedCrossRefGoogle Scholar
  93. 93.
    Orphanos V, McGown G, Hey Y et al (1995) Allelic imbalance of chromosome 6q in ovarian tumors. Br J Cancer 71:666–669PubMedGoogle Scholar
  94. 94.
    Hyyntinen ER, Saadut R, Chen C et al (2002) Defining the region(s) of deletion at 6q16–q22 in human prostate cancer. Genes Chromosomes Cancer 34:306–312CrossRefGoogle Scholar
  95. 95.
    Slade I, Stephens P, Douglas J et al (2010) Constitutional translocation breakpoint mapping by genome-wide paired-end sequencing identifies HACE1 as a putative Wilms tumor susceptibility gene. J Med Genet 47:342–347PubMedCrossRefGoogle Scholar
  96. 96.
    Ghanem MA, Van der Kwast TH, Den Hollander JC et al (2001) The prognostic significance of apoptosis-associated proteins BCL-2, BAX and BCL-X in clinical nephroblastoma. Br J Cancer 85:1557–1563PubMedCrossRefGoogle Scholar
  97. 97.
    Basta-Jovanovic G, Radonjic V, Stolic I et al (2005) Significance of proto-oncogene Bcl-XS/L expression in Wilms’ tumor. Renal Failure 1:13–18Google Scholar
  98. 98.
    Bardeesy N, Falkoff D, Petruzzi MH et al (1994) Anaplastic Wilms’ tumour, a subtype displaying poor prognosis, harbours p53 gene mutations. Nat Genet 7:91–97PubMedCrossRefGoogle Scholar
  99. 99.
    Zuppan CW, Beckwith JB, Luckey DW (1988) Anaplasia in unilateral Wilms’ tumor: a report from the National Wilms’ Tumor Study Pathology Center. Hum Pathol 19:1199–1209PubMedCrossRefGoogle Scholar
  100. 100.
    Beckwith JB, Palmer NF (1978) Histopathology and prognosis of Wilms tumor results from the first National Wilms’ Tumor Study. Cancer 41: 1937–1948PubMedCrossRefGoogle Scholar
  101. 101.
    Bonadio JF, Storer B, Norkool P et al (1985) Anaplastic Wilms’ tumor: clinical and pathological studies. J Clin Oncol 3:513–520PubMedGoogle Scholar
  102. 102.
    el Bahtimi R, Hazen-Martin DJ, Re GG et al (1996) Immunophenotype, mRNA expression, and gene structure of p53 in Wilms’ tumors. Mod Pathol 9:238–244PubMedGoogle Scholar
  103. 103.
    Scharnhorst V, Dekker P, van der Eb AJ, Jochemsen AG (2000) Physical interaction between Wilms tumor 1 and p73 proteins modulates their functions. J Biol Chem 275:10202–10211PubMedCrossRefGoogle Scholar
  104. 104.
    Maheswaran S, Park S, Bernard A et al (1993) Physical and functional interaction between WT1 and p53 proteins. Proc Natl Acad Sci U S A 90:5100–5104PubMedCrossRefGoogle Scholar
  105. 105.
    Wu Y, Mehew JW, Heckman CA et al (2001) Negative regulation of bcl-2 expression by p53 in hematopoietic cells. Oncogene 20:240–251PubMedCrossRefGoogle Scholar
  106. 106.
    Huang J, Soffer SZ, Kim ES et al (2002) p53 accumulation in favorable-histology Wilms tumor is associated with angiogenesis and clinically aggressive disease. J Pediatr Surg 37:523–527PubMedCrossRefGoogle Scholar
  107. 107.
    Henry I, Grandjouan S, Couillin P et al (1989) Tumor-specific loss of 11p15.5 alleles in del11p13 Wilms tumor and in familial adrenocortical carcinoma. Proc Natl Acad Sci U S A 86:3247–3251PubMedCrossRefGoogle Scholar
  108. 108.
    Koufos A, Grundy P, Morgan K et al (1989) Familial Wiedemann-Beckwith syndrome and a second Wilms tumor locus both map to 11p15.5. Am J Hum Genet 44:711–719PubMedGoogle Scholar
  109. 109.
    Ping AJ, Reeve AE, Law DJ et al (1989) Genetic linkage of Beckwith-Wiedemann syndrome to 11p15. Am J Hum Genet 44:720–723PubMedGoogle Scholar
  110. 110.
    Reeve AE, Sih SA, Raizis AM, Feinberg AP (1989) Loss of allelic heterozygosity at a second locus on chromosome 11 in sporadic Wilms’ tumor cells. Mol Cell Biol 9:1799–1803PubMedGoogle Scholar
  111. 111.
    Satoh Y, Nakadate H, Nakagawachi T et al (2006) Genetic and epigenetic alterations on the short arm of chromosome 11 are involved in a majority of sporadic Wilms’ tumours. Br J Cancer 95:541–547PubMedCrossRefGoogle Scholar
  112. 112.
    Pal N, Wadey RB, Buckle B et al (1990) Preferential loss of maternal alleles in sporadic Wilms’ tumour. Oncogene 5:1665–1668PubMedGoogle Scholar
  113. 113.
    Williams JC, Brown KW, Mott MG, Maitland NJ (1989) Maternal allele loss in Wilms’ tumour. Lancet 1:283–284PubMedCrossRefGoogle Scholar
  114. 114.
    Schroeder WT, Chao LY, Dao DD et al (1987) Nonrandom loss of maternal chromosome 11 alleles in Wilms’ tumors. Am J Hum Genet 40:413–420PubMedGoogle Scholar
  115. 115.
    Mannens M, Slater RM, Heyting C et al (1988) Molecular nature of genetic changes resulting in loss of heterozygosity of chromosome 1 in Wilms’ tumours. Hum Genet 81:41–48PubMedCrossRefGoogle Scholar
  116. 116.
    Ogawa O, Becroft DM, Morison IM et al (1993) Constitutional relaxation of insulin-like growth factor II gene imprinting associated with WIlms’ tumour and gigantism. Nat Genet 5:408–412PubMedCrossRefGoogle Scholar
  117. 117.
    Feinberg AP (1999) Imprinting of a genomic domain of 11p15 and loss of imprinting in cancer: an introduction. Cancer Res 59:1743s–1746sPubMedGoogle Scholar
  118. 118.
    Rainer S, Johnson L, Dobry C et al (1993) Relaxation of imprinted genes in human cancer. Nature 362:747–749CrossRefGoogle Scholar
  119. 119.
    Ogawa O, Eccles MR, Szeto J et al (1993) Relaxation of insulin-like growth factor II gene imprinting implicated in Wilms’ tumour. Nature 362:749–751PubMedCrossRefGoogle Scholar
  120. 120.
    Moulton T, Crenshaw T, Hao Y et al (1994) Epigenetic lesions at the H19 locus in Wilms’ tumour patients. Nat Genet 7:440–447PubMedCrossRefGoogle Scholar
  121. 121.
    Steenman MJ, Rainier S, Dobry CJ et al (1994) Loss of imprinting of IGF2 is linked to reduced expression and abnormal methylation of H19 in Wilms’ tumour. Nat Genet 7:433–439PubMedCrossRefGoogle Scholar
  122. 122.
    Algar EM, St. Heaps L, Darmanian A et al (2007) Paternally inherited submicroscopic duplicatin at 11p15.5 implicates insulin-like growth factor II in overgrowth and Wilms’ tumorigenesis. Cancer Res 67:2360–2365PubMedCrossRefGoogle Scholar
  123. 123.
    Mummert SK, Lobanenkov VA, Feinberg AP (2005) Association of chromosome arm 16q loss with loss of imprinting of insulin-like growth factor-II in Wilms tumor. Genes, Chromosomes & Cancer 43:155–161CrossRefGoogle Scholar
  124. 124.
    Watanabe N, Nakadate H, Haruta M et al (2006) Association of 11q loss, trisomy 12, and possible 16q loss with loss of imprinting of insulin-like growth factor II in Wilms tumor. Genes Chromosomes Cancer 45:592–601PubMedCrossRefGoogle Scholar
  125. 125.
    Rivera MN, Kim WJ, Wells J et al (2007) An X chromosome gene, WTX, is commonly inactivated in Wilms tumor. Science 315:642–645PubMedCrossRefGoogle Scholar
  126. 126.
    Carrel L, Willard HF (2005) X inactivation profile reveals extensive variability in X-linked gene expression in females. Nature 434:400–404PubMedCrossRefGoogle Scholar
  127. 127.
    Spreafico F, Terenziani M, Lualdi E et al (2007) Non-chromosome 11-p syndromes in Wilms tumor patients: clinical and cytogenetic report of two Down syndrome cases and one Turner syndrome case. Am J Med Genet 143:85–88PubMedCrossRefGoogle Scholar
  128. 128.
    Rivera MN, Kim WJ, Wells J et al (2009) The tumor suppressor WTX shuttles to the nucleus and modulates WT1 activity. Proc Natl Acad Sci U S A 106:8338–8343PubMedCrossRefGoogle Scholar
  129. 129.
    Hing S, Lu YJ, Summersgill B et al (2001) Gain of 1q is associated with adverse outcome in favourable histology Wilms tumor. Am J Pathol 158:393–398PubMedGoogle Scholar
  130. 130.
    Vajna R, Schramm M, Pereverzev A et al (1998) New isoform of neuronal Ca2+ channel α1 subunits in cell lines and tissues. Eur J Biochem 257:274–285PubMedCrossRefGoogle Scholar
  131. 131.
    Fridman E, Pinthus JH, Kopolovic J et al (2006) Expression of cyclooxygenase-2 in Wilms tumor: immunohistochemical study using tissue microarray methodology. J Urol 176:1747–1750PubMedCrossRefGoogle Scholar
  132. 132.
    Xu XC (2002) COX-2 inhibitors in cancer treatment and prevention, a recent development. Anticancer Drugs 13:127–137PubMedCrossRefGoogle Scholar
  133. 133.
    Pinthus JH, Fridman E, Dekel B et al (2004) ErbB2 is a tumor associated antigen and a suitable therapeutic target in Wilms tumor. J Urol 172:1644–1648PubMedCrossRefGoogle Scholar
  134. 134.
    Singh KP, Roy D (2006) SKCG-1: a new candidate growth regulatory gene at chromosome 11q23.2 in human sporadic Wilms tumours. Brit J Cancer 94:1524–1532PubMedCrossRefGoogle Scholar
  135. 135.
    Benetkiewicz M, Diaz de Stahl T, Gordor A et al (2006) Identification of limited regions of genetic aberrations in patients affected with Wilms’ tumor using a tiling-path chromosome 22 array. Int J Cancer 119:571–578PubMedCrossRefGoogle Scholar
  136. 136.
    Natrajan R, Williams DR, Grigoriadis A et al (2007) Delineation of a 1Mb breakpoint at 1p13 in Wilms tumors by fine-tiling oligonucleotide array CGH. Genes Chromosomes Cancer 46:607–615PubMedCrossRefGoogle Scholar
  137. 137.
    Williams RD, Hing SN, Greer BT et al (2004) Prognostic classification of relapsing favorable histology Wilms tumor using cDNA microarray expression profiling and support vector machines. Genes Chromosomes Cancer 41:65–79PubMedCrossRefGoogle Scholar
  138. 138.
    Bardeesy N, Beckwith JB, Pelletier J (1995) Clonal expansion and attenuated apoptosis in Wilms’ tumors are associated with p53 gene mutations. Cancer Res 55:215–219PubMedGoogle Scholar
  139. 139.
    Tretiakova M, Turkyilmaz M, Grushko T et al (2006) Topoisomerase IIα in Wilms’ tumour: gene alterations and immunoexpression. J Clin Pathol 59:1272–1277PubMedCrossRefGoogle Scholar
  140. 140.
    Amundson SA, Myers TG, Fornace Jr AJ (1998) Roles for p53 in growth arrest and apoptosis: putting on the brakes after genotoxic stress. Oncogene 17:3287–3299PubMedCrossRefGoogle Scholar
  141. 141.
    Schwartz D, Rotter V (1998) p53-dependent cell cycle control: response to genotoxic stress. Semin Cancer Biol 8:325–333PubMedCrossRefGoogle Scholar

Copyright information

© Feseo 2010

Authors and Affiliations

  • Christopher Blackmore
    • 1
  • Max J. Coppes
    • 2
  • Aru Narendran
    • 1
    Email author
  1. 1.Southern Alberta Children’s Cancer ProgramAlberta Children’s HospitalCalgaryCanada
  2. 2.Center for Cancer and Blood DisordersChildren’s National Medical CenterWashington, DCUSA

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