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Am J Pathol. Feb 1995; 146(2): 344–356.
PMCID: PMC1869867

Wilms' Tumor 1 Susceptibility (WT1) Gene Products are Selectively Expressed in Malignant Mesothelioma


The distinction between malignant mesothelioma and other neoplastic processes involving the pleura is difficult, partly due to the lack of specific markers expressed on mesothelioma. Because of evidence suggesting that the Wilms' tumor susceptibility gene (WT1), unlike ot her tumor suppressor genes, is restricted mostly to mesenchymaly derived tissues, we hypothesized that the WTI gene products could serve as a potential marker for mesothelioma. The expression of WTI mRNA was analyzed in 19 malignant mesothelioma cell lines and 9 tumors and compared with the expression of WT1 in 10 non-small cell lung cancer lines and 9 lung cancer specimens. WTI mRNA was detectable by Northern analysis in 16 of 19 mesothelioma cell lines and in 5 of 8 malignant mesothelioma tumors. In contrast, WTI mRNA was not detected by Northern analysis in non-small cell lung cancer lines or carcinomas. Immunoprecipitation with an anti-WT1 monoclonal antibody showed that a52-to 54-kdprotein was present in 4 mesothelioma cell lines. Immunostanig with this antibody localizd the WT1 protein to the nucleus in two mesothelioma lines and in 20 of 21 mesothelioma tumors examined. This distinctive pattern of nuclear immunoreactivity was absent in 26 non-mesothelioma tumors involving the lung, including 20 non-small cell lung carcinomas. The detection of WTI mRNA or protein may thus provide a specific molecular or immunohistochemical marker for differentiation of mesothelioma from other pleural tumors, inparticular, adenocarcinoma.

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  • Taguchi T, Jhanwar SC, Siegfried JM, Keller SM, Testa JR. Recurrent deletions of specific chromosomal sites in 1p, 3p, 6q, and 9p in human malignant mesothelioma. Cancer Res. 1993 Sep 15;53(18):4349–4355. [PubMed]
  • Ramael M, Deblier I, Eerdekens C, Lemmens G, Jacobs W, Van Marck E. Immunohistochemical staining of ras oncogene product in neoplastic and non-neoplastic mesothelial tissues: immunoreactivity for N-ras and lack of immunohistochemical staining for Ha-ras and K-ras. J Pathol. 1993 Apr;169(4):421–424. [PubMed]
  • Pisani RJ, Colby TV, Williams DE. Malignant mesothelioma of the pleura. Mayo Clin Proc. 1988 Dec;63(12):1234–1244. [PubMed]
  • Brown RW, Clark GM, Tandon AK, Allred DC. Multiple-marker immunohistochemical phenotypes distinguishing malignant pleural mesothelioma from pulmonary adenocarcinoma. Hum Pathol. 1993 Apr;24(4):347–354. [PubMed]
  • Weiss LM, Battifora H. The search for the optimal immunohistochemical panel for the diagnosis of malignant mesothelioma. Hum Pathol. 1993 Apr;24(4):345–346. [PubMed]
  • Call KM, Glaser T, Ito CY, Buckler AJ, Pelletier J, Haber DA, Rose EA, Kral A, Yeger H, Lewis WH, et al. Isolation and characterization of a zinc finger polypeptide gene at the human chromosome 11 Wilms' tumor locus. Cell. 1990 Feb 9;60(3):509–520. [PubMed]
  • Gessler M, Poustka A, Cavenee W, Neve RL, Orkin SH, Bruns GA. Homozygous deletion in Wilms tumours of a zinc-finger gene identified by chromosome jumping. Nature. 1990 Feb 22;343(6260):774–778. [PubMed]
  • Rauscher FJ., 3rd The WT1 Wilms tumor gene product: a developmentally regulated transcription factor in the kidney that functions as a tumor suppressor. FASEB J. 1993 Jul;7(10):896–903. [PubMed]
  • Maheswaran S, Park S, Bernard A, Morris JF, Rauscher FJ, 3rd, Hill DE, Haber DA. Physical and functional interaction between WT1 and p53 proteins. Proc Natl Acad Sci U S A. 1993 Jun 1;90(11):5100–5104. [PMC free article] [PubMed]
  • Klein G. Genes that can antagonize tumor development. FASEB J. 1993 Jul;7(10):821–825. [PubMed]
  • Armstrong JF, Pritchard-Jones K, Bickmore WA, Hastie ND, Bard JB. The expression of the Wilms' tumour gene, WT1, in the developing mammalian embryo. Mech Dev. 1993 Jan;40(1-2):85–97. [PubMed]
  • Park S, Schalling M, Bernard A, Maheswaran S, Shipley GC, Roberts D, Fletcher J, Shipman R, Rheinwald J, Demetri G, et al. The Wilms tumour gene WT1 is expressed in murine mesoderm-derived tissues and mutated in a human mesothelioma. Nat Genet. 1993 Aug;4(4):415–420. [PubMed]
  • Pritchard-Jones K, Fleming S, Davidson D, Bickmore W, Porteous D, Gosden C, Bard J, Buckler A, Pelletier J, Housman D, et al. The candidate Wilms' tumour gene is involved in genitourinary development. Nature. 1990 Jul 12;346(6280):194–197. [PubMed]
  • Coppes MJ, Campbell CE, Williams BR. The role of WT1 in Wilms tumorigenesis. FASEB J. 1993 Jul;7(10):886–895. [PubMed]
  • Haber DA, Park S, Maheswaran S, Englert C, Re GG, Hazen-Martin DJ, Sens DA, Garvin AJ. WT1-mediated growth suppression of Wilms tumor cells expressing a WT1 splicing variant. Science. 1993 Dec 24;262(5142):2057–2059. [PubMed]
  • Pelletier J, Schalling M, Buckler AJ, Rogers A, Haber DA, Housman D. Expression of the Wilms' tumor gene WT1 in the murine urogenital system. Genes Dev. 1991 Aug;5(8):1345–1356. [PubMed]
  • Zhou J, Rauscher FJ, 3rd, Bondy C. Wilms' tumor (WT1) gene expression in rat decidual differentiation. Differentiation. 1993 Sep;54(2):109–114. [PubMed]
  • Coppes MJ, Ye Y, Rackley R, Zhao XL, Liefers GJ, Casey G, Williams BR. Analysis of WT1 in granulosa cell and other sex cord-stromal tumors. Cancer Res. 1993 Jun 15;53(12):2712–2714. [PubMed]
  • Kreidberg JA, Sariola H, Loring JM, Maeda M, Pelletier J, Housman D, Jaenisch R. WT-1 is required for early kidney development. Cell. 1993 Aug 27;74(4):679–691. [PubMed]
  • Walker C, Rutten F, Yuan X, Pass H, Mew DM, Everitt J. Wilms' tumor suppressor gene expression in rat and human mesothelioma. Cancer Res. 1994 Jun 15;54(12):3101–3106. [PubMed]
  • Smythe WR, Kaiser LR, Hwang HC, Amin KM, Pilewski JM, Eck SJ, Wilson JM, Albelda SM. Successful adenovirus-mediated gene transfer in an in vivo model of human malignant mesothelioma. Ann Thorac Surg. 1994 Jun;57(6):1395–1401. [PubMed]
  • Mette SA, Pilewski J, Buck CA, Albelda SM. Distribution of integrin cell adhesion receptors on normal bronchial epithelial cells and lung cancer cells in vitro and in vivo. Am J Respir Cell Mol Biol. 1993 May;8(5):562–572. [PubMed]
  • Albelda SM, Daise M, Levine EM, Buck CA. Identification and characterization of cell-substratum adhesion receptors on cultured human endothelial cells. J Clin Invest. 1989 Jun;83(6):1992–2002. [PMC free article] [PubMed]
  • Morris JF, Madden SL, Tournay OE, Cook DM, Sukhatme VP, Rauscher FJ., 3rd Characterization of the zinc finger protein encoded by the WT1 Wilms' tumor locus. Oncogene. 1991 Dec;6(12):2339–2348. [PubMed]
  • Chomczynski P, Sacchi N. Single-step method of RNA isolation by acid guanidinium thiocyanate-phenol-chloroform extraction. Anal Biochem. 1987 Apr;162(1):156–159. [PubMed]
  • Nakajima-Iijima S, Hamada H, Reddy P, Kakunaga T. Molecular structure of the human cytoplasmic beta-actin gene: interspecies homology of sequences in the introns. Proc Natl Acad Sci U S A. 1985 Sep;82(18):6133–6137. [PMC free article] [PubMed]
  • Haber DA, Sohn RL, Buckler AJ, Pelletier J, Call KM, Housman DE. 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. [PMC free article] [PubMed]
  • Abate C, Luk D, Gentz R, Rauscher FJ, 3rd, Curran T. Expression and purification of the leucine zipper and DNA-binding domains of Fos and Jun: both Fos and Jun contact DNA directly. Proc Natl Acad Sci U S A. 1990 Feb;87(3):1032–1036. [PMC free article] [PubMed]
  • Gentz R, Chen CH, Rosen CA. Bioassay for trans-activation using purified human immunodeficiency virus tat-encoded protein: trans-activation requires mRNA synthesis. Proc Natl Acad Sci U S A. 1989 Feb;86(3):821–824. [PMC free article] [PubMed]
  • Knudsen KA, Horwitz AF, Buck CA. A monoclonal antibody identifies a glycoprotein complex involved in cell-substratum adhesion. Exp Cell Res. 1985 Mar;157(1):218–226. [PubMed]
  • Sharma PM, Bowman M, Madden SL, Rauscher FJ, 3rd, Sukumar S. RNA editing in the Wilms' tumor susceptibility gene, WT1. Genes Dev. 1994 Mar 15;8(6):720–731. [PubMed]
  • Sheibani K, Esteban JM, Bailey A, Battifora H, Weiss LM. Immunopathologic and molecular studies as an aid to the diagnosis of malignant mesothelioma. Hum Pathol. 1992 Feb;23(2):107–116. [PubMed]
  • Miwa H, Beran M, Saunders GF. Expression of the Wilms' tumor gene (WT1) in human leukemias. Leukemia. 1992 May;6(5):405–409. [PubMed]
  • Miyagi T, Ahuja H, Kubota T, Kubonishi I, Koeffler HP, Miyoshi I. Expression of the candidate Wilm's tumor gene, WT1, in human leukemia cells. Leukemia. 1993 Jul;7(7):970–977. [PubMed]
  • Bruening W, Gros P, Sato T, Stanimir J, Nakamura Y, Housman D, Pelletier J. Analysis of the 11p13 Wilms' tumor suppressor gene (WT1) in ovarian tumors. Cancer Invest. 1993;11(4):393–399. [PubMed]
  • Viel A, Giannini F, Capozzi E, Canzonieri V, Scarabelli C, Gloghini A, Boiocchi M. Molecular mechanisms possibly affecting WT1 function in human ovarian tumors. Int J Cancer. 1994 May 15;57(4):515–521. [PubMed]

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