wilms tumor genes


Summary: Genes at loci that are involved in the development of WILMS TUMOR. Included are human WT1 at 11p13 and human WT2 (MTACR1) at 11p15.

Top Publications

  1. Oji Y, Miyoshi Y, Koga S, Nakano Y, Ando A, Nakatsuka S, et al. Overexpression of the Wilms' tumor gene WT1 in primary thyroid cancer. Cancer Sci. 2003;94:606-11 pubmed
    ..These findings indicate an important role of the wild-type WT1 gene in the tumorigenesis of primary thyroid cancer. ..
  2. Pelletier J, Bruening W, Li F, Haber D, Glaser T, Housman D. WT1 mutations contribute to abnormal genital system development and hereditary Wilms' tumour. Nature. 1991;353:431-4 pubmed
    ..We now report constitutional mutations within the WT1 genes of two individuals with a combination of WT and genital abnormalities as evidence of a role for a recessive oncogene in mammalian development. ..
  3. Dome J, Coppes M. Recent advances in Wilms tumor genetics. Curr Opin Pediatr. 2002;14:5-11 pubmed
    ..Recurrent abnormalities of other loci, including 16q, 1p, and 7p, have indicated that these sites may harbor Wilms tumor genes. An enhanced understanding of these and other genetic lesions will provide the foundation for novel targeted ..
  4. Herzer U, Crocoll A, Barton D, Howells N, Englert C. The Wilms tumor suppressor gene wt1 is required for development of the spleen. Curr Biol. 1999;9:837-40 pubmed
  5. Ye Y, Raychaudhuri B, Gurney A, Campbell C, Williams B. Regulation of WT1 by phosphorylation: inhibition of DNA binding, alteration of transcriptional activity and cellular translocation. EMBO J. 1996;15:5606-15 pubmed
    ..Accordingly, phosphorylation may play a role in modulating the transcriptional regulatory activity of WT1 through interference with nuclear translocation, as well as by inhibition of WT1 DNA binding. ..
  6. Maheswaran S, Englert C, Zheng G, Lee S, Wong J, Harkin D, et al. Inhibition of cellular proliferation by the Wilms tumor suppressor WT1 requires association with the inducible chaperone Hsp70. Genes Dev. 1998;12:1108-20 pubmed
    ..These observations indicate that Hsp70 is an important cofactor for the function of WT1, and suggest a potential role for this chaperone during kidney differentiation. ..
  7. Fraizer G, Shimamura R, Zhang X, Saunders G. PAX 8 regulates human WT1 transcription through a novel DNA binding site. J Biol Chem. 1997;272:30678-87 pubmed
    ..Thus, we identified a novel functional binding site for the transcription factor PAX 8, suggesting that part of its role in kidney development may be as a modulator of WT1 expression in the kidney. ..
  8. Sharma P, Bowman M, Madden S, Rauscher F, Sukumar S. RNA editing in the Wilms' tumor susceptibility gene, WT1. Genes Dev. 1994;8:720-31 pubmed
    ..Edited WT1-C839 mRNA was barely detectable in neonatal kidney, whereas adult rat kidneys contained both U839 and C839-WT1 mRNA, suggesting a role for the two protein isoforms in growth and differentiation. ..
  9. Bruening W, Bardeesy N, Silverman B, Cohn R, Machin G, Aronson A, et al. Germline intronic and exonic mutations in the Wilms' tumour gene (WT1) affecting urogenital development. Nat Genet. 1992;1:144-8 pubmed
    ..These results provide genetic evidence for distinct functional roles of the WT1 isoforms in urogenital development. ..

More Information


  1. Kim J, Prawitt D, Bardeesy N, Torban E, Vicaner C, Goodyer P, et al. The Wilms' tumor suppressor gene (wt1) product regulates Dax-1 gene expression during gonadal differentiation. Mol Cell Biol. 1999;19:2289-99 pubmed
    ..In addition, we demonstrate that WT1 can activate the endogenous Dax-1 promoter. Our results indicate that the WT1-DAX-1 pathway is an early event in the process of mammalian sex determination. ..
  2. McConnell M, Cunliffe H, Chua L, Ward T, Eccles M. Differential regulation of the human Wilms tumour suppressor gene (WT1) promoter by two isoforms of PAX2. Oncogene. 1997;14:2689-700 pubmed
    ..A fragment containing the -205/-230 site alone could be transactivated by PAX2. These findings suggest that PAX2 is a tissue-specific modulator of WT1 expression, and is involved in cell growth control via WT1. ..
  3. Hylander B, Repasky E, Shrikant P, Intengan M, Beck A, Driscoll D, et al. Expression of Wilms tumor gene (WT1) in epithelial ovarian cancer. Gynecol Oncol. 2006;101:12-7 pubmed
    ..Since WT1 demonstrates tissue-restricted expression and is inherently immunogenic, it could represent an attractive target for antigen-specific immunotherapy in EOC. ..
  4. Wagner K, Cooper W, Grundy R, Caldwell G, Jones C, Wadey R, et al. Frequent RASSF1A tumour suppressor gene promoter methylation in Wilms' tumour and colorectal cancer. Oncogene. 2002;21:7277-82 pubmed
    ..We have demonstrated that RASSF1A inactivation is the most frequent genetic or epigenetic event yet reported in Wilms' tumourigenesis and that allelotyping studies may fail to identify regions containing important TSGs. ..
  5. Ruteshouser E, Hendrickson B, Colella S, Krahe R, Pinto L, Huff V. Genome-wide loss of heterozygosity analysis of WT1-wild-type and WT1-mutant Wilms tumors. Genes Chromosomes Cancer. 2005;43:172-80 pubmed
    ..Our results implicate 9q22.2-q31.1 as a region containing such a gene. ..
  6. Nachtigal M, Hirokawa Y, Enyeart VanHouten D, Flanagan J, Hammer G, Ingraham H. Wilms' tumor 1 and Dax-1 modulate the orphan nuclear receptor SF-1 in sex-specific gene expression. Cell. 1998;93:445-54 pubmed
    ..We propose that WT1 and Dax-1 functionally oppose each other in testis development by modulating SF-1-mediated transactivation. ..
  7. Englert C, Hou X, Maheswaran S, Bennett P, Ngwu C, Re G, et al. WT1 suppresses synthesis of the epidermal growth factor receptor and induces apoptosis. EMBO J. 1995;14:4662-75 pubmed
    ..Repression of EGFR and induction of apoptosis by mechanism that may contribute to its critical role in normal kidney development and to the immortalization of tumor cells with inactivated WT1 alleles. ..
  8. Rackley R, Flenniken A, Kuriyan N, Kessler P, Stoler M, Williams B. Expression of the Wilms' tumor suppressor gene WT1 during mouse embryogenesis. Cell Growth Differ. 1993;4:1023-31 pubmed
    ..Interestingly, there is also WT1 expression in the central nervous system which localizes to the ependymal layer of the ventral aspect of the spinal cord.(ABSTRACT TRUNCATED AT 250 WORDS) ..
  9. Ogawa O, Becroft D, Morison I, Eccles M, Skeen J, Mauger D, et al. Constitutional relaxation of insulin-like growth factor II gene imprinting associated with Wilms' tumour and gigantism. Nat Genet. 1993;5:408-12 pubmed
    ..These findings suggest that a defect in genomic imprinting can occur constitutionally, leading to growth abnormalities and predisposition to Wilms' tumour...
  10. Shimamura R, Fraizer G, Trapman J, Lau YfC -, Saunders G. The Wilms' tumor gene WT1 can regulate genes involved in sex determination and differentiation: SRY, Müllerian-inhibiting substance, and the androgen receptor. Clin Cancer Res. 1997;3:2571-80 pubmed
    ..The results of these functional and binding assays suggest that WT1 has an important role in regulation of genes involved in embryonal sexual development and that WT1 can function as a transcriptional activator. ..
  11. Loeb D, Evron E, Patel C, Sharma P, Niranjan B, Buluwela L, et al. Wilms' tumor suppressor gene (WT1) is expressed in primary breast tumors despite tumor-specific promoter methylation. Cancer Res. 2001;61:921-5 pubmed
    ..Our results demonstrate expression of WT1 in mammary neoplasia, and that WT1 may not have a tumor suppressor role in breast cancer. ..
  12. Hammes A, Guo J, Lutsch G, Leheste J, Landrock D, Ziegler U, et al. Two splice variants of the Wilms' tumor 1 gene have distinct functions during sex determination and nephron formation. Cell. 2001;106:319-29 pubmed
    ..Our data demonstrate distinct functions for the two splice variants and place the +KTS variants as important regulators for Sry in the sex determination pathway. ..
  13. Discenza M, Vaz D, Hassell J, Pelletier J. Activation of the WT1 tumor suppressor gene promoter by Pea3. FEBS Lett. 2004;560:183-91 pubmed
    ..Our results position Pea3 upstream of WT1 and define a gene hierarchy important for mesenchymal-epithelial transitions. ..
  14. Oka Y, Tsuboi A, Taguchi T, Osaki T, Kyo T, Nakajima H, et al. Induction of WT1 (Wilms' tumor gene)-specific cytotoxic T lymphocytes by WT1 peptide vaccine and the resultant cancer regression. Proc Natl Acad Sci U S A. 2004;101:13885-90 pubmed
    ..It was therefore demonstrated that WT1 vaccination could induce WT1-specific cytotoxic T lymphocytes and result in cancer regression without damage to normal tissues. ..
  15. Johnstone R, See R, Sells S, Wang J, Muthukkumar S, Englert C, et al. A novel repressor, par-4, modulates transcription and growth suppression functions of the Wilms' tumor suppressor WT1. Mol Cell Biol. 1996;16:6945-56 pubmed
    ..Significantly, par-4, but not a mutant unable to interact with WT1, rescued growth suppression caused by WT1. Thus, we identified a novel repressor that modulates transcription as well as growth suppression functions of WT1. ..
  16. Englert C. WT1--more than a transcription factor?. Trends Biochem Sci. 1998;23:389-93 pubmed
  17. Martinerie C, Chevalier G, Rauscher F, Perbal B. Regulation of nov by WT1: a potential role for nov in nephrogenesis. Oncogene. 1996;12:1479-92 pubmed
    ..The downregulation of novH expression by WT1 might represent a key element in normal and tumoral nephrogenesis. ..
  18. Rivera M, Haber D. Wilms' tumour: connecting tumorigenesis and organ development in the kidney. Nat Rev Cancer. 2005;5:699-712 pubmed
    ..Our understanding of the roles of WT1 in tumour formation and organogenesis have advanced in parallel, providing a striking example of the intersection between tumour biology, cellular differentiation and normal organogenesis. ..
  19. Yang L, Han Y, Suarez Saiz F, Saurez Saiz F, Minden M. A tumor suppressor and oncogene: the WT1 story. Leukemia. 2007;21:868-76 pubmed
    ..To understand the mechanism by which WT1 can do this, we will also examine its functional activity as a transcription factor and the influence of protein partners on its dual behavior. ..
  20. Lee S, Haber D. Wilms tumor and the WT1 gene. Exp Cell Res. 2001;264:74-99 pubmed
    ..Understanding the distinct functional properties of WT1 isoforms and tumor-associated variants will provide unique insight into the link between normal organ-specific differentiation and malignancy. ..
  21. Little M, Wells C. A clinical overview of WT1 gene mutations. Hum Mutat. 1997;9:209-25 pubmed
    ..WT1 mutations have also been reported in juvenile granulosa cell tumour, non-asbestos related mesothelioma, desmoplastic small round cell tumour and, most recently, acute myeloid leukemia. ..
  22. Ueda T, Oji Y, Naka N, Nakano Y, Takahashi E, Koga S, et al. Overexpression of the Wilms' tumor gene WT1 in human bone and soft-tissue sarcomas. Cancer Sci. 2003;94:271-6 pubmed
  23. Oji Y, Yano M, Nakano Y, Abeno S, Nakatsuka S, Ikeba A, et al. Overexpression of the Wilms' tumor gene WT1 in esophageal cancer. Anticancer Res. 2004;24:3103-8 pubmed
    ..The WT1 protein was overexpressed in 5 (45%) out of 11 mild dysplasia and in 8 (89%) out of 9 moderate to severe dysplasia. These results may indicate an important role of the WT1 gene in the tumorigenesis of ESCC. ..
  24. Oji Y, Yamamoto H, Nomura M, Nakano Y, Ikeba A, Nakatsuka S, et al. Overexpression of the Wilms' tumor gene WT1 in colorectal adenocarcinoma. Cancer Sci. 2003;94:712-7 pubmed
    ..These results may indicate an important role of the wild-type WT1 gene in tumorigenesis of colorectal adenocarcinoma. ..
  25. Satoh Y, Nakadate H, Nakagawachi T, Higashimoto K, Joh K, Masaki Z, et al. Genetic and epigenetic alterations on the short arm of chromosome 11 are involved in a majority of sporadic Wilms' tumours. Br J Cancer. 2006;95:541-7 pubmed
    ..5 and/or 11p13. One-third of the tumours had alterations at multiple loci. Our results suggest that chromosome 11p is not only genetically but also epigenetically critical for the majority of Wilms' tumours. ..
  26. Cohen H, Bossone S, Zhu G, McDonald G, Sukhatme V. Sp1 is a critical regulator of the Wilms' tumor-1 gene. J Biol Chem. 1997;272:2901-13 pubmed
    ..This work suggests abundant Sp1 may be a prerequisite for WT1 expression, and that Sp1 may have a wider role in nephrogenesis. ..
  27. Oji Y, Suzuki T, Nakano Y, Maruno M, Nakatsuka S, Jomgeow T, et al. Overexpression of the Wilms' tumor gene W T1 in primary astrocytic tumors. Cancer Sci. 2004;95:822-7 pubmed
    ..These results may indicate that the W T1 gene plays an important role in tumorigenesis of primary astrocytic tumors. ..
  28. Rupprecht H, Drummond I, Madden S, Rauscher F, Sukhatme V. The Wilms' tumor suppressor gene WT1 is negatively autoregulated. J Biol Chem. 1994;269:6198-206 pubmed
    ..These observations emphasize its critical role as a transcriptional regulatory protein during normal kidney development. ..
  29. Dehbi M, Pelletier J. PAX8-mediated activation of the wt1 tumor suppressor gene. EMBO J. 1996;15:4297-306 pubmed
  30. Regev M, Kirk R, Mashevich M, Bistritzer Z, Reish O. Vertical transmission of a mutation in exon 1 of the WT1 gene: lessons for genetic counseling. Am J Med Genet A. 2008;146A:2332-6 pubmed publisher
    ..Explorative laparoscopy for sex organ evaluation and gonadal assessment for possible gonadoblastoma should be considered when constitutional mutation is detected in males with GU anomalies. ..
  31. Morrison D, English M, Licht J. WT1 induces apoptosis through transcriptional regulation of the proapoptotic Bcl-2 family member Bak. Cancer Res. 2005;65:8174-82 pubmed
    ..These data support the hypothesis that Wilms' tumors arise, in part, because WT1 mutant proteins fail to promote programmed cell death during kidney development. ..
  32. Brunelli J, Robison B, Thorgaard G. Ancient and recent duplications of the rainbow trout Wilms' tumor gene. Genome. 2001;44:455-62 pubmed
    ..The WT1 genes of one family map to linkage groups 6 and 27 in the trout genome map. Reverse transcribed polymerase chain reaction (RT-PCR) expression analysis demonstrated little difference in W..
  33. Zamora Avila D, Franco Molina M, Trejo Avila L, Rodriguez Padilla C, Resendez Perez D, Zapata Benavides P. RNAi silencing of the WT1 gene inhibits cell proliferation and induces apoptosis in the B16F10 murine melanoma cell line. Melanoma Res. 2007;17:341-8 pubmed
    ..Together, these findings implicate decreased WT1 protein levels in the induction of apoptosis. These results imply that WT1 plays a distinct role in B16F10 melanoma growth. ..
  34. Webster N, Kong Y, Sharma P, Haas M, Sukumar S, Seely B. Differential effects of Wilms tumor WT1 splice variants on the insulin receptor promoter. Biochem Mol Med. 1997;62:139-50 pubmed
    ..Deletional mapping indicated that distinct regions of the IR promoter mediated the effects of the two isoforms and DNaseI footprint analysis identified potential WT1 binding sites within these regions. ..
  35. Kanato K, Hosen N, Yanagihara M, Nakagata N, Shirakata T, Nakazawa T, et al. The Wilms' tumor gene WT1 is a common marker of progenitor cells in fetal liver. Biochem Biophys Res Commun. 2005;326:836-43 pubmed
    ..These results indicated that WT1 expression is a common marker of both hepatocyte and endothelial progenitors. These results also implied a role of the WT1 gene in lineage determination. ..
  36. Liu J, Nau M, Yeh J, Allegra C, Chu E, Wright J. Molecular heterogeneity and function of EWS-WT1 fusion transcripts in desmoplastic small round cell tumors. Clin Cancer Res. 2000;6:3522-9 pubmed
    ..The molecular diversity and functionality exhibited by these fusion transcripts may have significant biological implications for their transactivating and tumorigenic potential. ..
  37. Olszewski M, Huang W, Chou P, Duerst R, Kletzel M. Wilms' tumor 1 (WT1) gene in hematopoiesis: a surrogate marker of cell proliferation as a possible mechanism of action?. Cytotherapy. 2005;7:57-61 pubmed
  38. Saglio G, Carturan S, Grillo S, Capella S, Arruga F, Defilippi I, et al. WT1 overexpression: a clinically useful marker in acute and chronic myeloid leukemias. Hematology. 2005;10 Suppl 1:76-8 pubmed
  39. Ozaltin F, Heeringa S, Poyraz C, Bilginer Y, Kadayifcilar S, Besbas N, et al. Eye involvement in children with primary focal segmental glomerulosclerosis. Pediatr Nephrol. 2008;23:421-7 pubmed
    ..Ophthalmologic evaluation at the time of diagnosis might be beneficial to characterize further the spectrum of this possible association. ..
  40. Haltia A, Solin M, Muramatsu T, Jalanko H, Holmberg C, Miettinen A, et al. Expression of nine developmental stage-specific genes in human kidney and cultured renal cells. Exp Nephrol. 1997;5:457-64 pubmed
    ..Some genes thought to be only transiently expressed during kidney maturation were, however, constantly found in the samples from fetal to newborn and adult kidneys. ..
  41. Baird P, Pritchard J, Cowell J. Molecular genetic analysis of chromosome 11p in familial Wilms tumour. Br J Cancer. 1994;69:1072-7 pubmed
  42. Okutsu T, Kuroiwa Y, Kagitani F, Kai M, Aisaka K, Tsutsumi O, et al. Expression and imprinting status of human PEG8/IGF2AS, a paternally expressed antisense transcript from the IGF2 locus, in Wilms' tumors. J Biochem. 2000;127:475-83 pubmed
    ..These findings indicate that PEG8/IGF2AS is a good marker of Wilms' tumor and also suggest the possibility of PEG8/IGF2AS being one of the candidate Wilms' tumor genes. ..
  43. Hohenstein P, Hastie N. The many facets of the Wilms' tumour gene, WT1. Hum Mol Genet. 2006;15 Spec No 2:R196-201 pubmed
  44. Tsurutani N, Oda H, Nakatsuru Y, Imai Y, Zhang S, Ueno Y, et al. cDNA cloning and developmental expression of the porcine homologue of WT1. Gene. 1998;211:215-20 pubmed
    ..Therefore, swines could provide good models for analyzing the contributions of WT1 gene to genitourinary development and genesis of Wilms' tumors. ..
  45. Andrade J, Guaragna M, Soardi F, Guerra Junior G, Mello M, Maciel Guerra A. Clinical and genetic findings of five patients with WT1-related disorders. Arq Bras Endocrinol Metabol. 2008;52:1236-43 pubmed
  46. Johnstone R, Wang J, Tommerup N, Vissing H, Roberts T, Shi Y. Ciao 1 is a novel WD40 protein that interacts with the tumor suppressor protein WT1. J Biol Chem. 1998;273:10880-7 pubmed
    ..Thus, Ciao 1 appears to specifically modulate the transactivation activity of WT1 and may function to regulate the physiological functions of WT1 in cell growth and differentiation. ..
  47. Dao D, Walsh C, Yuan L, Gorelov D, Feng L, Hensle T, et al. Multipoint analysis of human chromosome 11p15/mouse distal chromosome 7: inclusion of H19/IGF2 in the minimal WT2 region, gene specificity of H19 silencing in Wilms' tumorigenesis and methylation hyper-dependence of H19 imprinting. Hum Mol Genet. 1999;8:1337-52 pubmed
    ..Pre-existing massive allelic asymmetry for DNA methylation and hyper-dependence of transcription on methylation status may underlie the mechanism of gene-specific silencing of H19 in Wilms' tumorigenesis. ..
  48. Sakamoto J, Takata A, Fukuzawa R, Kikuchi H, Sugiyama M, Kanamori Y, et al. A novel WT1 gene mutation associated with wilms' tumor and congenital male genitourinary malformation. Pediatr Res. 2001;50:337-44 pubmed
    ..These results, together with the data from previous reports, suggest that WT1 may function in gonadogenesis, nephrogenesis, and Wilms' tumor tumorigenesis. ..
  49. Zhou W, Boucher R, Bollig F, Englert C, Hildebrandt F. Characterization of mesonephric development and regeneration using transgenic zebrafish. Am J Physiol Renal Physiol. 2010;299:F1040-7 pubmed publisher
    ..This suggests that wt1b may serve as an early marker of fated renal progenitor cells. The synchronous nature of regenerative neonephrogenesis suggests that this process may be useful for studies of nephron development. ..
  50. Saatci C, Caglayan A, Kocyigit I, Akalin H, Kaynar L, Altuntas F, et al. Expression of WT1 gene in multiple myeloma patients at diagnosis: is WT1 gene expression a useful marker in multiple myeloma?. Hematology. 2010;15:39-42 pubmed publisher
    ..On this basis WT1 expression analyses is unlikely to be a useful genetic marker for routine clinical use in multiple myeloma patients at diagnosis. ..
  51. Geller J. Genetic stratification of Wilms tumor: is WT1 gene analysis ready for prime time?. Cancer. 2008;113:893-6 pubmed publisher
  52. Schumacher V, Gueler B, Looijenga L, Becker J, Amann K, Engers R, et al. Characteristics of testicular dysgenesis syndrome and decreased expression of SRY and SOX9 in Frasier syndrome. Mol Reprod Dev. 2008;75:1484-94 pubmed publisher
    ..To further study the function of human Sertoli cells in the future, we have established a human cell line. ..
  53. Bliek J, Gicquel C, Maas S, Gaston V, Le Bouc Y, Mannens M. Epigenotyping as a tool for the prediction of tumor risk and tumor type in patients with Beckwith-Wiedemann syndrome (BWS). J Pediatr. 2004;145:796-9 pubmed
    ..It also is possible to predict whether they are at risk of developing a Wilms' tumor. Epigenotyping of patients is important to select the type of screening protocol to be proposed to these patients. ..