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. 1998 Jan 1;26(1):271–274. doi: 10.1093/nar/26.1.271

Software and database for the analysis of mutations in the human WT1 gene.

C Jeanpierre 1, C Béroud 1, P Niaudet 1, C Junien 1
PMCID: PMC147190  PMID: 9399851

Abstract

The WT1 gene, located at 11p13, encodes a zinc finger transcription factor involved in renal and gonadal development and in Wilms' tumor. Constitutional mutations of this gene have been described in most patients with Denys Drash syndrome (mesangial sclerosis associated with male pseudohermaphrodism and/or Wilms' tumor), but also in patients with genitourinary abnormalities and Wilms' tumor (WT) or presenting with only unilateral or bilateral WT. Moreover, approximately 10% of Wilms' tumors carry WT1 mutations at the somatic level. To facilitate the genotype-phenotype correlation analyses, we have created a software package along with a computerized database of germline (70 entries) and somatic (28 entries) mutations reported in the literature.

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Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Akasaka Y., Kikuchi H., Nagai T., Hiraoka N., Kato S., Hata J. A point mutation found in the WT1 gene in a sporadic Wilms' tumor without genitourinary abnormalities is identical with the most frequent point mutation in Denys-Drash syndrome. FEBS Lett. 1993 Feb 8;317(1-2):39–43. doi: 10.1016/0014-5793(93)81487-k. [DOI] [PubMed] [Google Scholar]
  2. Baird P. N., Cowell J. K. A novel zinc finger mutation in a patient with Denys-Drash syndrome. Hum Mol Genet. 1993 Dec;2(12):2193–2194. doi: 10.1093/hmg/2.12.2193. [DOI] [PubMed] [Google Scholar]
  3. Baird P. N., Groves N., Haber D. A., Housman D. E., Cowell J. K. Identification of mutations in the WT1 gene in tumours from patients with the WAGR syndrome. Oncogene. 1992 Nov;7(11):2141–2149. [PubMed] [Google Scholar]
  4. Baird P. N., Santos A., Groves N., Jadresic L., Cowell J. K. Constitutional mutations in the WT1 gene in patients with Denys-Drash syndrome. Hum Mol Genet. 1992 Aug;1(5):301–305. doi: 10.1093/hmg/1.5.301. [DOI] [PubMed] [Google Scholar]
  5. Bardeesy N., Zabel B., Schmitt K., Pelletier J. WT1 mutations associated with incomplete Denys-Drash syndrome define a domain predicted to behave in a dominant-negative fashion. Genomics. 1994 Jun;21(3):663–664. doi: 10.1006/geno.1994.1333. [DOI] [PubMed] [Google Scholar]
  6. Bickmore W. A., Oghene K., Little M. H., Seawright A., van Heyningen V., Hastie N. D. Modulation of DNA binding specificity by alternative splicing of the Wilms tumor wt1 gene transcript. Science. 1992 Jul 10;257(5067):235–237. doi: 10.1126/science.1321494. [DOI] [PubMed] [Google Scholar]
  7. Bruening W., Bardeesy N., Silverman B. L., Cohn R. A., Machin G. A., Aronson A. J., Housman D., Pelletier J. Germline intronic and exonic mutations in the Wilms' tumour gene (WT1) affecting urogenital development. Nat Genet. 1992 May;1(2):144–148. doi: 10.1038/ng0592-144. [DOI] [PubMed] [Google Scholar]
  8. Cariello N. F., Cui L., Beroud C., Soussi T. Database and software for the analysis of mutations in the human p53 gene. Cancer Res. 1994 Aug 15;54(16):4454–4460. [PubMed] [Google Scholar]
  9. Clarkson P. A., Davies H. R., Williams D. M., Chaudhary R., Hughes I. A., Patterson M. N. Mutational screening of the Wilms's tumour gene, WT1, in males with genital abnormalities. J Med Genet. 1993 Sep;30(9):767–772. doi: 10.1136/jmg.30.9.767. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Collod-Béroud G., Béroud C., Ades L., Black C., Boxer M., Brock D. J., Holman K. J., de Paepe A., Francke U., Grau U. Marfan Database (third edition): new mutations and new routines for the software. Nucleic Acids Res. 1998 Jan 1;26(1):229–223. doi: 10.1093/nar/26.1.229. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Collod-Béroud G., Béroud C., Adès L., Black C., Boxer M., Brock D. J., Godfrey M., Hayward C., Karttunen L., Milewicz D. Marfan Database (second edition): software and database for the analysis of mutations in the human FBN1 gene. Nucleic Acids Res. 1997 Jan 1;25(1):147–150. doi: 10.1093/nar/25.1.147. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Coppes M. J., Campbell C. E., Williams B. R. The role of WT1 in Wilms tumorigenesis. FASEB J. 1993 Jul;7(10):886–895. doi: 10.1096/fasebj.7.10.8393819. [DOI] [PubMed] [Google Scholar]
  13. Coppes M. J., Campbell C. E., Williams B. R. The role of WT1 in Wilms tumorigenesis. FASEB J. 1993 Jul;7(10):886–895. doi: 10.1096/fasebj.7.10.8393819. [DOI] [PubMed] [Google Scholar]
  14. Coppes M. J., Liefers G. J., Higuchi M., Zinn A. B., Balfe J. W., Williams B. R. Inherited WT1 mutation in Denys-Drash syndrome. Cancer Res. 1992 Nov 1;52(21):6125–6128. [PubMed] [Google Scholar]
  15. Coppes M. J., Liefers G. J., Paul P., Yeger H., Williams B. R. Homozygous somatic Wt1 point mutations in sporadic unilateral Wilms tumor. Proc Natl Acad Sci U S A. 1993 Feb 15;90(4):1416–1419. doi: 10.1073/pnas.90.4.1416. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Devriendt K., Deloof E., Moerman P., Legius E., Vanhole C., de Zegher F., Proesmans W., Devlieger H. Diaphragmatic hernia in Denys-Drash syndrome. Am J Med Genet. 1995 May 22;57(1):97–101. doi: 10.1002/ajmg.1320570120. [DOI] [PubMed] [Google Scholar]
  17. Drummond I. A., Madden S. L., Rohwer-Nutter P., Bell G. I., Sukhatme V. P., Rauscher F. J., 3rd Repression of the insulin-like growth factor II gene by the Wilms tumor suppressor WT1. Science. 1992 Jul 31;257(5070):674–678. doi: 10.1126/science.1323141. [DOI] [PubMed] [Google Scholar]
  18. Drummond I. A., Rupprecht H. D., Rohwer-Nutter P., Lopez-Guisa J. M., Madden S. L., Rauscher F. J., 3rd, Sukhatme V. P. DNA recognition by splicing variants of the Wilms' tumor suppressor, WT1. Mol Cell Biol. 1994 Jun;14(6):3800–3809. doi: 10.1128/mcb.14.6.3800. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Gessler M., König A., Arden K., Grundy P., Orkin S., Sallan S., Peters C., Ruyle S., Mandell J., Li F. Infrequent mutation of the WT1 gene in 77 Wilms' Tumors. Hum Mutat. 1994;3(3):212–222. doi: 10.1002/humu.1380030307. [DOI] [PubMed] [Google Scholar]
  20. Gessler M., König A., Moore J., Qualman S., Arden K., Cavenee W., Bruns G. Homozygous inactivation of WT1 in a Wilms' tumor associated with the WAGR syndrome. Genes Chromosomes Cancer. 1993 Jul;7(3):131–136. doi: 10.1002/gcc.2870070304. [DOI] [PubMed] [Google Scholar]
  21. Haber D. A., Sohn R. L., Buckler A. J., Pelletier J., Call K. M., Housman D. E. Alternative splicing and genomic structure of the Wilms tumor gene WT1. Proc Natl Acad Sci U S A. 1991 Nov 1;88(21):9618–9622. doi: 10.1073/pnas.88.21.9618. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Hastie N. D. Wilms' tumour gene and function. Curr Opin Genet Dev. 1993 Jun;3(3):408–413. doi: 10.1016/0959-437x(93)90113-4. [DOI] [PubMed] [Google Scholar]
  23. Huff V. Genotype/phenotype correlations in Wilms' tumor. Med Pediatr Oncol. 1996 Nov;27(5):408–414. doi: 10.1002/(SICI)1096-911X(199611)27:5<408::AID-MPO4>3.0.CO;2-Q. [DOI] [PubMed] [Google Scholar]
  24. Huff V., Jaffe N., Saunders G. F., Strong L. C., Villalba F., Ruteshouser E. C. WT1 exon 1 deletion/insertion mutations in Wilms tumor patients, associated with di- and trinucleotide repeats and deletion hotspot consensus sequences. Am J Hum Genet. 1995 Jan;56(1):84–90. [PMC free article] [PubMed] [Google Scholar]
  25. Kaplinsky C., Ghahremani M., Frishberg Y., Rechavi G., Pelletier J. Familial Wilms' tumor associated with a WT1 zinc finger mutation. Genomics. 1996 Dec 15;38(3):451–453. doi: 10.1006/geno.1996.0655. [DOI] [PubMed] [Google Scholar]
  26. Larsson S. H., Charlieu J. P., Miyagawa K., Engelkamp D., Rassoulzadegan M., Ross A., Cuzin F., van Heyningen V., Hastie N. D. Subnuclear localization of WT1 in splicing or transcription factor domains is regulated by alternative splicing. Cell. 1995 May 5;81(3):391–401. doi: 10.1016/0092-8674(95)90392-5. [DOI] [PubMed] [Google Scholar]
  27. Little M. H., Prosser J., Condie A., Smith P. J., Van Heyningen V., Hastie N. D. Zinc finger point mutations within the WT1 gene in Wilms tumor patients. Proc Natl Acad Sci U S A. 1992 Jun 1;89(11):4791–4795. doi: 10.1073/pnas.89.11.4791. [DOI] [PMC free article] [PubMed] [Google Scholar]
  28. Little M. H., Williamson K. A., Mannens M., Kelsey A., Gosden C., Hastie N. D., van Heyningen V. Evidence that WT1 mutations in Denys-Drash syndrome patients may act in a dominant-negative fashion. Hum Mol Genet. 1993 Mar;2(3):259–264. doi: 10.1093/hmg/2.3.259. [DOI] [PubMed] [Google Scholar]
  29. Little M., Holmes G., Bickmore W., van Heyningen V., Hastie N., Wainwright B. DNA binding capacity of the WT1 protein is abolished by Denys-Drash syndrome WT1 point mutations. Hum Mol Genet. 1995 Mar;4(3):351–358. doi: 10.1093/hmg/4.3.351. [DOI] [PubMed] [Google Scholar]
  30. Little M., Wells C. A clinical overview of WT1 gene mutations. Hum Mutat. 1997;9(3):209–225. doi: 10.1002/(SICI)1098-1004(1997)9:3<209::AID-HUMU2>3.0.CO;2-2. [DOI] [PubMed] [Google Scholar]
  31. Moffett P., Bruening W., Nakagama H., Bardeesy N., Housman D., Housman D. E., Pelletier J. Antagonism of WT1 activity by protein self-association. Proc Natl Acad Sci U S A. 1995 Nov 21;92(24):11105–11109. doi: 10.1073/pnas.92.24.11105. [DOI] [PMC free article] [PubMed] [Google Scholar]
  32. Nordenskjöld A., Fricke G., Anvret M. Absence of mutations in the WT1 gene in patients with XY gonadal dysgenesis. Hum Genet. 1995 Jul;96(1):102–104. doi: 10.1007/BF00214195. [DOI] [PubMed] [Google Scholar]
  33. Nordenskjöld A., Friedman E., Anvret M. WT1 mutations in patients with Denys-Drash syndrome: a novel mutation in exon 8 and paternal allele origin. Hum Genet. 1994 Feb;93(2):115–120. doi: 10.1007/BF00210593. [DOI] [PubMed] [Google Scholar]
  34. Nordenskjöld A., Friedman E., Sandstedt B., Söderhäll S., Anvret M. Constitutional and somatic mutations in the WT1 gene in Wilms' tumor patients. Int J Cancer. 1995 Nov 15;63(4):516–522. doi: 10.1002/ijc.2910630410. [DOI] [PubMed] [Google Scholar]
  35. Ogawa O., Eccles M. R., Yun K., Mueller R. F., Holdaway M. D., Reeve A. E. A novel insertional mutation at the third zinc finger coding region of the WT1 gene in Denys-Drash syndrome. Hum Mol Genet. 1993 Feb;2(2):203–204. doi: 10.1093/hmg/2.2.203. [DOI] [PubMed] [Google Scholar]
  36. Park S., Bernard A., Bove K. E., Sens D. A., Hazen-Martin D. J., Garvin A. J., Haber D. A. Inactivation of WT1 in nephrogenic rests, genetic precursors to Wilms' tumour. Nat Genet. 1993 Dec;5(4):363–367. doi: 10.1038/ng1293-363. [DOI] [PubMed] [Google Scholar]
  37. Park S., Tomlinson G., Nisen P., Haber D. A. Altered trans-activational properties of a mutated WT1 gene product in a WAGR-associated Wilms' tumor. Cancer Res. 1993 Oct 15;53(20):4757–4760. [PubMed] [Google Scholar]
  38. Pelletier J., Bruening W., Kashtan C. E., Mauer S. M., Manivel J. C., Striegel J. E., Houghton D. C., Junien C., Habib R., Fouser L. Germline mutations in the Wilms' tumor suppressor gene are associated with abnormal urogenital development in Denys-Drash syndrome. Cell. 1991 Oct 18;67(2):437–447. doi: 10.1016/0092-8674(91)90194-4. [DOI] [PubMed] [Google Scholar]
  39. Pelletier J., Bruening W., Li F. P., Haber D. A., Glaser T., Housman D. E. WT1 mutations contribute to abnormal genital system development and hereditary Wilms' tumour. Nature. 1991 Oct 3;353(6343):431–434. doi: 10.1038/353431a0. [DOI] [PubMed] [Google Scholar]
  40. Poulat F., Morin D., König A., Brun P., Giltay J., Sultan C., Dumas R., Gessler M., Berta P. Distinct molecular origins for Denys-Drash and Frasier syndromes. Hum Genet. 1993 Apr;91(3):285–286. doi: 10.1007/BF00218274. [DOI] [PubMed] [Google Scholar]
  41. Quek H. H., Chow V. T., Tock E. P. The third zinc finger of the WT1 gene is mutated in Wilms' tumour but not in a broad range of other urogenital tumours. Anticancer Res. 1993 Sep-Oct;13(5A):1575–1580. [PubMed] [Google Scholar]
  42. Rupprecht H. D., Drummond I. A., Madden S. L., Rauscher F. J., 3rd, Sukhatme V. P. The Wilms' tumor suppressor gene WT1 is negatively autoregulated. J Biol Chem. 1994 Feb 25;269(8):6198–6206. [PubMed] [Google Scholar]
  43. Sakai A., Tadokoro K., Yanagisawa H., Nagafuchi S., Hoshikawa N., Suzuki T., Kohsaka T., Hasegawa T., Nakahori Y., Yamada M. A novel mutation of the WT1 gene (a tumor suppressor gene for Wilms' tumor) in a patient with Denys-Drash syndrome. Hum Mol Genet. 1993 Nov;2(11):1969–1970. doi: 10.1093/hmg/2.11.1969. [DOI] [PubMed] [Google Scholar]
  44. Schumacher V., Schneider S., Figge A., Wildhardt G., Harms D., Schmidt D., Weirich A., Ludwig R., Royer-Pokora B. Correlation of germ-line mutations and two-hit inactivation of the WT1 gene with Wilms tumors of stromal-predominant histology. Proc Natl Acad Sci U S A. 1997 Apr 15;94(8):3972–3977. doi: 10.1073/pnas.94.8.3972. [DOI] [PMC free article] [PubMed] [Google Scholar]
  45. Tsuda M., Sakiyama T., Kitagawa T., Watanabe S., Watanabe T., Takahashi S., Kawaguchi H., Ito K. Molecular analysis of two Japanese cases of Denys-Drash syndrome. J Inherit Metab Dis. 1993;16(5):876–880. doi: 10.1007/BF00714282. [DOI] [PubMed] [Google Scholar]
  46. Varanasi R., Bardeesy N., Ghahremani M., Petruzzi M. J., Nowak N., Adam M. A., Grundy P., Shows T. B., Pelletier J. Fine structure analysis of the WT1 gene in sporadic Wilms tumors. Proc Natl Acad Sci U S A. 1994 Apr 26;91(9):3554–3558. doi: 10.1073/pnas.91.9.3554. [DOI] [PMC free article] [PubMed] [Google Scholar]
  47. Varret M., Rabès J. P., Collod-Béroud G., Junien C., Boileau C., Béroud C. Software and database for the analysis of mutations in the human LDL receptor gene. Nucleic Acids Res. 1997 Jan 1;25(1):172–180. doi: 10.1093/nar/25.1.172. [DOI] [PMC free article] [PubMed] [Google Scholar]
  48. Varret M., Rabés J. P., Thiart R., Kotze M. J., Baron H., Cenarro A., Descamps O., Ebhardt M., Hondelijn J. C., Kostner G. M. LDLR Database (second edition): new additions to the database and the software, and results of the first molecular analysis. Nucleic Acids Res. 1998 Jan 1;26(1):248–252. doi: 10.1093/nar/26.1.248. [DOI] [PMC free article] [PubMed] [Google Scholar]
  49. Wang Z. Y., Madden S. L., Deuel T. F., Rauscher F. J., 3rd The Wilms' tumor gene product, WT1, represses transcription of the platelet-derived growth factor A-chain gene. J Biol Chem. 1992 Nov 5;267(31):21999–22002. [PubMed] [Google Scholar]
  50. Wang Z. Y., Qiu Q. Q., Deuel T. F. The Wilms' tumor gene product WT1 activates or suppresses transcription through separate functional domains. J Biol Chem. 1993 May 5;268(13):9172–9175. [PubMed] [Google Scholar]
  51. Wang Z. Y., Qiu Q. Q., Huang J., Gurrieri M., Deuel T. F. Products of alternatively spliced transcripts of the Wilms' tumor suppressor gene, wt1, have altered DNA binding specificity and regulate transcription in different ways. Oncogene. 1995 Feb 2;10(3):415–422. [PubMed] [Google Scholar]
  52. Webb N. J., Lewis M. A., Williamson K., van Heyningen V., Bruce J., Lendon M., Postlethwaite R. J. Do children with diffuse mesangial sclerosis in association with mutations of the Wilm's tumour suppressor gene (WT1) require bilateral nephrectomy? Pediatr Nephrol. 1995 Apr;9(2):252–253. doi: 10.1007/BF00860765. [DOI] [PubMed] [Google Scholar]

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