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Anaplastic Wilms' tumour, a subtype displaying poor prognosis, harbours p53 gene mutations

Nature Genetics volume 7, pages 91–97 (1994)Cite this article

Abstract

The genetics of Wilms' tumour (WT), a paediatric malignancy of the kidney, is complex. Inactivation of the tumour suppressor gene, WT1, is associated with tumour aetiology in ∼10–15% of WTs. Chromosome 17p changes have been noted in cytogenetic studies of WTs, prompting us to screen 140 WTs for p53 mutations. When histopathology reports were available, p53 mutations were present in eight of eleven anaplastic WTs, a tumour subtype associated with poor prognosis. Amplification of MDM2, a gene whose product binds and sequesters p53, was excluded. Our results indicate that p53 alterations provide a molecular marker for anaplastic WTs.

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References

  1. Matsunaga, E. Genetics of Wilms' tumour. Hum Genet. 57, 231–246 (1981).

    Article  CAS  PubMed  Google Scholar 

  2. Miller, R.W., Fraumeni, J.F.,Jr., & Manning, M.D. Association of Wilms' tumour with aniridia, hemihypertrophy and other congenital malformations. New Eng1. J. Med. 270, 922–927 (1964).

    Article  CAS  Google Scholar 

  3. Denys, P., Malvaux, P., van den Berghe, H., Tanghe, W. & Proesmans, W. Association d'un syndrome anatomo-pathologique de pseudohérmaphrodisme mascuiin, d'une tumeur de Wilms, d'une néphropathie parenchymateuse et d'un mosalcisme XX/XY. Arch. Fran. Ped. 24, 729–739 (1967).

    CAS  Google Scholar 

  4. Drash, A., Sherman, F., Hartmann, W.H. & Blizzard, R.M. A syndrome of pseudohermaphrodltism, Wilms' tumour, hypertension, and degenerative renal disease. J. Ped. 76, 585–593 (1970).

    Article  CAS  Google Scholar 

  5. Wiedemann, H.R. Complexe malformatif familial avec hernie ombilicale et macroglossie- Un syndrome nouveau? J. Génét. Hum. 13, 223–232 (1964).

    CAS  PubMed  Google Scholar 

  6. Riccardi, V.M., Sujansky, E., Smith, A.C. & Francke, U. Chromosomal imbalance in the aniridia/Wilms' tumour association: 11 p interstitial deletion. Pediatrics 61, 604–610 (1978).

    CAS  PubMed  Google Scholar 

  7. Call, K.M. et al. Isolation and characterization of a zinc finger polypeptide gene at the human chromosome 11 Wilms' tumour locus. Cell 60, 509–520 (1990).

    Article  CAS  PubMed  Google Scholar 

  8. Gessler, M. et al. Homozygous deletion in Wilms' tumours of a zinc-finger gene identified by chromosome jumping. Nature 343, 774–778 (1990).

    Article  CAS  PubMed  Google Scholar 

  9. Pelletier, J. et al. Germline mutations in the Wilms' tumour suppressor gene are associated with abnormal urogenital development in Denys-Drash syndrome. Cell 67, 437–447 (1991).

    Article  CAS  PubMed  Google Scholar 

  10. Bruening, W. et al. Germline intronic and exonic mutations in the Wilms' tumour gene (WT1) affecting urogenital development. Nature Genet. 1, 144–148 (1992).

    Article  CAS  PubMed  Google Scholar 

  11. Pelletier, J. et al. Genetic evidence implicating the Wilms' tumour gene (WT1) in genitourinary development. Nature 353, 431–434 (1991).

    Article  CAS  PubMed  Google Scholar 

  12. Pelletier, J., Munroe, D. & Housman, D. . in Genome Analysis Vol 3: Genes & Phenotypes (eds Davies, K.E. & Tilghman, S.M.) 135–169 (Cold Spring Harbor Laboratory Press, New York, 1991).

    Google Scholar 

  13. Maw, M.A. et al. A third Wilms' tumour locus on chromosome 16q. Cancer Res. 52, 3094–3098 (1992).

    CAS  PubMed  Google Scholar 

  14. Knudson, A.G. Mutation and cancer: a statistical study. Proc. natn. Acad. Sci. U.S.A. 68, 820–823 (1971).

    Article  Google Scholar 

  15. Levine, A.J., Momand, J. & Finlay, C.A. The p53 tumour suppressor gene. Nature 351, 453–456 (1991).

    Article  CAS  PubMed  Google Scholar 

  16. Hollstein, M., Sidransky, D., Vogelstein, B. & Harris, C.C. p53 Mutations in human cancers. Science 253, 49–53 (1991).

    Article  CAS  PubMed  Google Scholar 

  17. Lowe, S.W., Schmitt, E.M., Smith, S.W., Osborne, B.A. & Jacks, T. p53 is required for radiation-induced apoptosis in mouse thymocytes. Nature 362, 847–849 (1993).

    Article  CAS  PubMed  Google Scholar 

  18. Clarke, A.R. et al. Thymocyte apoptosis induced by p53-dependent and independent pathways. Nature 362, 849–852 (1993).

    Article  CAS  PubMed  Google Scholar 

  19. Lowe, S.W., Ruley, H.E., Jacks, T. & Housman, D.E. p53-dependent apoptosis modulates the cytotoxicity of anticancer agents. Cell 74, 957–967 (1993).

    Article  CAS  PubMed  Google Scholar 

  20. D'Angio, G.J. et al. Treatment of Wilms' tumour. Results from the third National Wilms' tumour study. Cancer 64, 349–360 (1989).

    Article  CAS  PubMed  Google Scholar 

  21. Murakami, Y., Hayashi, K. & Sekiya, T. Detection of aberrations of the p53 alleles and the gene transcript in human tumour cell lines by single-strand conformation polymorphism analysis. Cancer Res. 51, 3356–3361 (1991).

    CAS  PubMed  Google Scholar 

  22. Zuppan, C.W., Beckwith, J.B. & Luckey, D.W. Anaplasia in unilateral Wilms' tumour: a report from the national Wilms' tumour study pathology center. Hum. Path. 19, 1199–1209 (1988).

    Article  CAS  PubMed  Google Scholar 

  23. Oliner, J.D., Kinzler, K.W., Meltzer, P.S., George, D.L. & Vogelstein, B. Amplification of a gene encoding a p53-associated protein in human sarcomas. Nature 358, 80–83 (1992).

    Article  CAS  PubMed  Google Scholar 

  24. Ladanyi, M. et al. MDM2 gene amplification in metastatic osteosarcoma. Cancer Res. 53, 16–18 (1993).

    CAS  PubMed  Google Scholar 

  25. Reifenberger, G., Liu, L., Ichimura, K., Schmidt, E.E. & Collins, V.P. Amplification and overexpression of the MDM2 gene in a subset of human malignant gliomas without p53 mutations. Cancer Res. 53, 2736–2739 (1993).

    CAS  PubMed  Google Scholar 

  26. Dittmer, D. et al. Gain of function mutations in p53. Nature Genet. 4, 42–45 (1993).

    Article  CAS  PubMed  Google Scholar 

  27. de Fromentel, C.C. & Soussi, T. TP53 tumour suppressor gene: a model for investigating human mutagenesis. Genes. Chrom. Cancer 4, 1–15 (1992).

    Article  Google Scholar 

  28. Malkin, D. et al. Germ line p53 mutations in a familial syndrome of breast cancer, sarcomas, and other neoplasms. Science 250, 1233–1238 (1990).

    Article  CAS  PubMed  Google Scholar 

  29. Srivastava, S., Zhiquiang, Z., Pirollo, K., Blattner, W. & Chang, E.H. Germ-line transmission of a mutated p53 gene in a cancer-prone family with Li-Fraumeni syndrome. Nature 348, 747–749 (1990).

    Article  CAS  PubMed  Google Scholar 

  30. Hartley, A.L. et al. Wilms' tumour in the Li-Fraumeni cancer family syndrome. Cancer Genet. Cytogenet. 67, 133–135 (1993).

    Article  CAS  PubMed  Google Scholar 

  31. Ladd, W.E. Embryoma of the kidney (Wilms tumour). Ann. Surg. 108, 885–902 (1938).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  32. Gross, R.E. & Neuhauser, E.B.D. Treatment of mixed tumours of kidney in childhood. Pediatrics 6, 843–852 (1950).

    CAS  PubMed  Google Scholar 

  33. Lemoine, N.R., Hughes, C.M. & Cowell, J.K. Aberrant expression of the tumour suppressor gene p53 is very frequent in Wilms' tumours. J. Path. 168, 237–242 (1992).

    Article  CAS  PubMed  Google Scholar 

  34. Lowe, S.W. & Ruley, H.E. Stabilization of the p53 tumour suppressor is induced by adenovirus E1A and accompanies apoptosis. Genes Dev. 7, 535–545 (1993).

    Article  CAS  PubMed  Google Scholar 

  35. Maheswaran, S. et al. Physical and functional interaction between WT1 and p53 proteins. Proc. natn. Acad. Sci. U.S.A. 90, 5100–5104 (1993).

    Article  CAS  Google Scholar 

  36. Donehower, L.A. et al. Mice deficient for p53 are developmentally normal but susceptible to spontaneous tumours. Nature 356, 215–221 (1992).

    Article  CAS  PubMed  Google Scholar 

  37. Kreideberg, J.A. et al. WT-1 is required for early kidney development. Cell 74, 679–691 (1993).

    Article  Google Scholar 

  38. Jackson, D.P., Hayden, J.D. & Quirke, P. in PCR — A Practical Approach (eds., McPherson, M.J., Quirke, P. & Taylor, G.R.) 29–50 (Oxford University Press, Oxford, 1992).

    Google Scholar 

  39. Sanger, A.F., Nicklen, S. & Coulson, A.R. DNA sequencing with chain-terminating inhibitors. Proc. natn. Acad. Sci. U.S.A. 74, 5463–5467 (1977).

    Article  CAS  Google Scholar 

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Authors and Affiliations

  1. Department of Biochemistry, McGill University, 3655 Drummond St., Montreal, H3G 1Y6, Canada

    Nabeel Bardeesy, David Falkoff & Jerry Pelletier

  2. RoswellPark Memorial Institute, State University of New York at Buffalo, New York, 14263, USA

    Mary-Jane Petruzzi, Norma Nowak & Tom Shows

  3. Department of Pediatrics, University of Mainz, Langenbeck Str. 1, Mainz, D-6500, Germany

    Bernhard Zabel

  4. Department of Molecular Biology, Merck-Frosst Center for Therapeutic Research, P.O. Box 1005, Pointe Claire-Dorval, Quebec, H9R 4P8, Canada

    Mohammed Adam

  5. Izaak Walton Killam Children's Hospital, 5850 University Aveue, P.O. Box 3070, Halifax, Nova Scotia, B3J 3G9, Canada

    Maria C. Aguiar

  6. Molecular Oncology Program, Cross Cancer Institute, 11560 University Avenue, Edmonton, Alberta, T6G 1Z2, Canada

    Paul Grundy

  7. McGill Cancer Center, McGill University, 3655 Drummond St., Montreal, H3G 1Y6, Canada

    Jerry Pelletier

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Bardeesy, N., Falkoff, D., Petruzzi, MJ. et al. Anaplastic Wilms' tumour, a subtype displaying poor prognosis, harbours p53 gene mutations. Nat Genet 7, 91–97 (1994). https://doi.org/10.1038/ng0594-91

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