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  • Oncogenomics
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Hypomethylation and hypermethylation of DNA in Wilms tumors

Oncogene volume 21, pages 6694–6702 (2002)Cite this article

Abstract

We quantitatively analysed hypermethylation at CpG islands in the 5′ ends of 12 genes and one non-CpG island 5′ region (MTHFR) in 31 Wilms tumors. We also determined their global genomic 5-methylcytosine content. Compared with various normal postnatal tissues, ∼40–90% of these pediatric kidney cancers were hypermethylated in four of the genes, MCJ, RASSF1A, TNFRSF12 and CALCA as determined by a quantitative bisulfite-based assay (MethyLight). Interestingly, the non-CpG island 5′ region of MTHFR was less methylated in most tumors relative to the normal tissues. By chromatographic analysis of DNA digested to deoxynucleosides, about 60% of the Wilms tumors were found to be deficient in their overall levels of DNA methylation. We also analysed expression of the three known functional DNA methyltransferase genes. No relationship was observed between global genomic 5-methylcytosine levels and relative amounts of RNA for DNA methyltransferases DNMT1, DNMT3A, and DNMT3B. Importantly, no association was seen between CpG island hypermethylation and global DNA hypomethylation in these cancers. Therefore, the overall genomic hypomethylation frequently observed in cancers is probably not just a response or a prelude to hypermethylation elsewhere in the genome. This suggests that the DNA hypomethylation contributes independently to oncogenesis or tumor progression.

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References

  • Ahuja N, Li Q, Mohan AL, Baylin SB, Issa JP . 1998 Cancer Res. 58: 5489–5494

  • Arcellana-Panlilio MY, Egeler RM, Ujack E, Pinto A, Demetrick DJ, Robbins SM, Coppes MJ . 2000 Genes Chromosomes Cancer 29: 63–69

  • Baylin SB, Herman JG . 2000 DNA Alterations in Cancer: Genetic and Epigenetic Alterations Ehrlich M (ed). Natick: Eaton Publishing pp. 293–309

  • Burbee DG, Forgacs E, Zochbauer-Muller S, Shivakumar L, Fong K, Gao B, Randle D, Kondo M, Virmani A, Bader S, Sekido Y, Latif F, Milchgrub S, Toyooka S, Gazdar AF, Lerman MI, Zabarovsky E, White M, Minna JD . 2001 J. Natl. Cancer Inst. 93: 691–699

  • Busson P, Zhang Q, Guillon JM, Gregory CD, Young LS, Clausse B, Lipinski M, Rickinson AB, Tursz T . 1992 Int. J. Cancer 50: 863–867

  • Chapman V, Forrester L, Sanford J, Hastie N, Rossant J . 1984 Nature 307: 284–286

  • Cheng P, Schmutte C, Cofer KF, Felix JC, Yu MC, Dubeau L . 1997 Br. J. Cancer 75: 396–402

  • Dreijerink K, Braga E, Kuzmin I, Geil L, Duh FM, Angeloni D, Zbar B, Lerman MI, Stanbridge EJ, Minna JD, Protopopov A, Li J, Kashuba V, Klein G, Zabarovsky ER . 2001 Proc. Natl. Acad. Sci. USA 98: 7504–7509

  • Eads CA, Danenberg KD, Kawakami K, Saltz LB, Danenberg PV, Laird PW . 1999 Cancer Res. 59: 2302–2306

  • Eads CA, Danenberg KD, Kawakami K, Saltz LB, Blake C, Shibata D, Danenberg PV, Laird PW . 2000 Nucleic Acids Res. 28: E32

  • Eads CA, Lord RV, Wickramasinghe K, Long TI, Kurumboor SK, Bernstein L, Peters JH, DeMeester SR, DeMeester TR, Skinner KA, Laird PW . 2001 Cancer Res. 61: 3410–3418

  • Ehrlich M . 2000 DNA Alterations in Cancer: Genetic and Epigenetic Changes. Ehrlich M (ed). Natick: Eaton Publishing pp. 273–291

  • Ehrlich M . 2002 Oncogene 21: 5400–5413

  • Ehrlich M, Hopkins N, Jiang G, Dome J, Yu M, Woods C, Tomlinson G, Chintagumpala M, Champagne M, Diller L, Parham D, Sawyer J . 2002 Cancer Genet. Cytogenet. in press

  • Ehrlich M, Gama-Sosa M, Huang L-H, Midgett RM, Kuo KC, McCune RA, Gehrke C . 1982 Nucleic Acids Res. 10: 2709–2721

  • Feinberg AP, Vogelstein B . 1983 Nature 301: 89–92

  • Gama-Sosa MA, Slagel VA, Trewyn RW, Oxenhandler R, Kuo KC, Gehrke CW, Ehrlich M . 1983 Nucleic Acids Res. 11: 6883–6894

  • Gardiner-Garden M, Frommer M . 1987 J. Mol. Biol. 196: 261–282

  • Gaughan DJ, Barbaux S, Kluijtmans LA, Whitehead AS . 2000 Gene 257: 279–289

  • Grenet J, Valentine V, Kitson J, Li H, Farrow SN, Kidd VJ . 1998 Genomics 49: 385–393

  • Harada K, Toyooka S, Maitra A, Maruyama R, Toyooka KO, Timmons CF, Tomlinson GE, Maslrangel D, Hay RJ, Minna JD, Gazdar AF . 2002 Oncogene 21: 4345–4349

  • Hollander M, Wolfe DA . 1973 Nonparametric Statistical Methods. New York: John Wiley and Sons pp 68–75 and 191–194

  • Issa JP . 2000 DNA Alterations in Cancer: Genetic and Epigenetic Alterations. Ehrlich M (ed). Natick: Eaton Publishing pp. 311–322

  • Issa JP, Vertino PM, Boehm CD, Newsham IF, Baylin SB . 1996 Proc. Natl. Acad. Sci. USA 93: 11757–11762

  • Malik K, Salpekar A, Hancock A, Moorwood K, Jackson S, Charles A, Brown KW . 2000 Cancer Res. 60: 2356–2360

  • Mares J, Kriz V, Weinhausel A, Vodickova S, Kodet R, Haas OA, Sedlacek Z, Goetz P . 2001 Cancer Lett. 166: 165–171

  • Narayan A, Ji W, Zhang XY, Marrogi A, Graff JR, Baylin SB, Ehrlich M . 1998 Int. J. Cancer 77: 833–838

  • Oswald J, Engemann S, Lane N, Mayer W, Olek A, Fundele R, Dean W, Reik W, Walter J . 2000 Curr. Biol. 10: 475–478

  • Qu G, Dubeau L, Narayan A, Yu M, Ehrlich M . 1999a Mut. Res. 423: 91–101

  • Qu G, Grundy PE, Narayan A, Ehrlich M . 1999b Cancer Genet. Cytogenet. 109: 34–39

  • Razin A, Kafri T . 1994 Prog. Nucleic Acid Res. Mol. Biol. 48: 53–81

  • Ribieras S, Song-Wang X-G, Martin V, Lointier P, Frappart L, Dante R . 1994 J. Cell Biochem. 56: 86–96

  • Santos F, Hendrich B, Reik W, Dean W . 2002 Dev. Biol. 241: 172–182

  • Shridhar V, Bible KC, Staub J, Avula R, Lee YK, Kalli K, Huang H, Hartmann LC, Kaufmann SH, Smith DI . 2001 Cancer Res. 61: 4258–4265

  • Strichman-Almashanu LZ, Lee RS, Onyango PO, Perlman E, Flam F, Frieman MB, Feinberg AP . 2002 Genome Res. 12: 543–554

  • Toyota M, Shen L, Ohe-Toyota M, Hamilton SR, Sinicrope FA, Issa JP . 2000 Cancer Res. 60: 4044–4048

  • Tuck-Muller CM, Narayan A, Tsien F, Smeets D, Sawyer J, Fiala ES, Sohn O, Ehrlich M . 2000 Cytogen. Cell Genet. 89: 121–128

  • Tycko B . 2000 DNA and Alterations in Cancer: Genetic and Epigenetic Alterations. Ehrlich M (ed). Natick: Eaton Publishing pp. 333–349

  • Ushijima T, Morimura K, Hosoya Y, Okonogi H, Tatematsu M, Sugimura T, Nagao M . 1997 Proc. Natl. Acad. Sci. USA 94: 2284–2289

  • Wang EC, Kitson J, Thern A, Williamson J, Farrow SN, Owen MJ . 2001 Immunogenetics 53: 59–63

  • Wong N, Lam WC, Lai PB, Pang E, Lau WY, Johnson PJ . 2001 Am. J. Pathol. 159: 465–471

  • Yung R, Ray D, Eisenbraun JK, Deng C, Attwood J, Eisenbraun MD, Johnson K, Miller RA, Hanash S, Richardson B . 2001 J. Gerontol. A Biol. Sci. Med. Sci. 56: B268–B276

  • Zhang X-Y, Loflin PT, Gehrke CW, Andrews PA, Ehrlich M . 1987 Nucleic Acids Res. 15: 9429–9449

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Acknowledgements

We are very grateful to Michael Jaynes, Darla Tate, Shirley Waldon, Martine Therrien, Michelle Maguigad, and Cheryl Medeiros-Nancarrow for invaluable help in collecting tumor samples and obtaining clinical information. We thank Kazuko Arakawa for her assistance in statistical computing. This work was supported in part by NIH grants CA 81506 (to M Ehrlich), CA 75090 (to PW Laird), and PO1 CA 46589 and PO1 CA 70972 (to E Fiala).

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Authors and Affiliations

  1. Tulane Cancer Center and Human Genetics Program, Tulane Medical School, New Orleans, 70112, Louisiana, LA, USA

    Melanie Ehrlich & Guanchao Jiang

  2. Department of Biochemical Pharmacology, American Health Foundation, Valhalla, New York, 10595, NY, USA

    Emerich Fiala, Byungwoo Youn & Ock-Soon Sohn

  3. Department of Hematology/Oncology, St. Jude Children's Research Hospital, Memphis, 38105, Tennessee, TN, USA

    Jeffrey S Dome

  4. Department of Preventive Medicine, University of Southern California, Norris Comprehensive Cancer Center, Los Angeles, 90033, California, CA, USA

    Mimi C Yu

  5. Department of Surgery, University of Southern California, Norris Comprehensive Cancer Center, Los Angeles, 90033, California, CA, USA

    Tiffany I Long, Martin Widschwendter & Peter W Laird

  6. Department of Biochemistry and Molecular Biology, University of Southern California, Norris Comprehensive Cancer Center, Los Angeles, 90033, California, CA, USA

    Tiffany I Long, Martin Widschwendter, Gangning Liang & Peter W Laird

  7. Department of Pediatrics, University of Texas Southwestern Medical Center, Dallas, 75235, Texas, TX, USA

    Gail E Tomlinson

  8. Texas Children's Cancer Center, Baylor College of Medicine, Houston, 77030, Texas, TX, USA

    Murali Chintagumpala

  9. Service D'hematologie Oncologie, Hopital Sainte-Justine, Montreal, H3T 1C5, Quebec, Canada

    Martin Champagne

  10. Department of Pathology, Arkansas Children's Hospital and University of Arkansas for Medical Sciences, Little Rock, 72205, Arkansas, AR, USA

    David Parham

  11. Department of Pathology, Cancer & Leukaemia in Childhood Unit, School of Medical Sciences, University of Bristol, Bristol, BS8 1TD, UK

    Karim Malik

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  1. Melanie Ehrlich
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Correspondence to Melanie Ehrlich.

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Ehrlich, M., Jiang, G., Fiala, E. et al. Hypomethylation and hypermethylation of DNA in Wilms tumors. Oncogene 21, 6694–6702 (2002). https://doi.org/10.1038/sj.onc.1205890

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