• Iftikhar Qayum
  • Muhammad Ashraf


Background: The DNA Methyltransferase 1 (DNMT1) gene is among the better known ‘epigenetic’ systems that can regulate normal and abnormal gene expression as well as create ‘hot spots’ for DNA mutations. Its role has been studied in a number of malignancies with important implications for involvement in early events of malignant transformation. The present study describes the findings with respect to expression of this gene in human lymphomas studied by Fluorescent In Situ Hybridization (FISH). Method: The study was undertaken on randomly selected archival human lymph nodes comprising 50 specimens of normal or reactive lymph nodes and 50 specimens of lymphoma lymph nodes. These were subjected to FISH using oligonucleotide Antisense probes for the DNMT1 mRNA according to standard FISH protocols. Percent cells stained, mean ‘dots’ stained per cell and staining signal intensity were taken as the criteria for comparing control and lymphoma lymph nodes. Quantitation of probe signals was done both by manual visualisation of the fluorescent signals and computer based image analysis. Results: Data indicated a significantly increased expression of the DNMT1 mRNA in lymphoma cases as compared to controls (p<0.001). Conclusion: This implies a possible role of the DNMT1 gene in transformation / oncogenesis in human lymphomas.Key Words: DNA methyltransferases, FISH, lymphomas.


Jones PA. DNA methylation errors and cancer. Cancer Res 1966; 56: 2643-67.

Wachsman JT. DNA methylation and the association between genetic and epigenetic changes: relation to carcinogenesis. Mut Res 1997; 375: 1-8.

Baylin SB, Herman JG, Graff JR, Vertino PM, Issa JP. Alterations in DNA methylation: a fundamental aspect of neoplasia. Adv Cancer Res 1998;72:141-96.

Herman JG, Baylin SB. Promoter-region hypermethylation and gene silencing in human cancer. Curr Top Microbiol Immunol 2000; 249: 35-54.

Robertson KD, Wolffe AP. DNA methylation in health and disease. Nat Rev Genet 2000;1: 11-9.

Sutherland JE, Costa M. DNA methylation and gene silencing. In: Heuvel JPV, Perdew GH, Mattes WB, Greenlee WF (Eds.). Comprehensive Toxicology, vol xiv, Somerset UK: Elsevier Science BV 2002. pp 299-310.

Okano M, Bell DW, Haber DA, Li E. DNA methyltransferases Dnmt3a and Dnmt3b are essential for de novo methylation and mammalian development. Cell 1999; 99: 247-57.

Robertson KD, Uzvolgyi E, Liang G, Talmadge C, Sumegi J, Gonzales FA et al. The human DNA methyltransferases (DNMTs) 1, 3a and 3b: coordinate mRNA expression in normal tissues and over expression in tumors. Nucleic Acids Res 1999; 27: 2291-8.

Issa JP, Baylin SB, Herman JG. DNA methylation changes in hematologic malignancies: biologic and clinical implications. Leukemia 1997; 11 (Suppl 1): S7‑11.

Moller MB, Ino Y, Gerdes AM, Skjodt K, Louis DN, Pedersen NT. Aberrations of the p53 pathway components p53, MDM2 and CDKN2A appear independent in diffuse large B cell lymphoma. Leukemia 1999; 13(3): 453‑9.

Corn PG, Kuerbitz SJ, van Noesel MM, Esteller M, Compitello N, Baylin SB et al. Transcriptional silencing of the p73 gene in acute lymphoblastic leukemia and Burkitt's lymphoma is associated with 5' CpG island methylation. Cancer Res 1999; 59(14): 3352‑6.

Kawano S, Miller CW, Gombart AF, Bartram CR, Matsuo Y, Asou H et al. Loss of p73 gene expression in leukemias / lymphomas due to hypermethylation. Blood 1999; 94(3): 1113‑20.

Melki JR, Warnecke P, Vincent PC, Clark SJ. Increased DNA methyltransferase expression in leukaemia. Leukemia 1998; 12(3): 311‑6.

Issa JP, Vertino PM, Wu J, Sazawal S, Celano P, Nelkin BD et al. Increased cytosine DNA-methyltransferase activity during colon cancer progression. J Nat Cancer Inst 1993; 85: 1235-40.

Bakin AV, Curran T. Role of DNA 5-methylcytosine transferase in cell transformation by fos. Science 1999; 283: 387-90.

Lutsenko E, Bhagwat AS. Principal causes of hot spots for cytosine to thymine mutations at sites of cytosine methylation in growing cells. A model, its experimental support and implications. Mutat Res 1999;437(1): 11‑20.

Lehr HA, Jacobs TW, Yaziji H, Schnitt SJ, Gown AM. Quantitative evaluation of HER-2/neu status in breast cancer by Fluorescence In Situ Hybridization and by immunohistochemistry with image analysis. Am J Clin Pathology 2001; 115(6): 814-22.

Wiedorn KH, Kuhl H, Galle J, Caselitz J, Vollmer E. Comparison of in-situ hybridization, direct and indirect in-situ PCR as well as tyramide signal amplification for the detection of HPV. Histochem Cell Biol 1999; 111: 89-95.

Dirks RW. RNA molecules lighting up under the microscope. Histochem Cell Biol 1996; 106: 151-66.

Speel EJM. Detection and amplification systems for sensitive, multiple-target DNA and RNA in situ hybridization: looking inside cells with a spectrum of colors. Histochem Cell Biol 1999; 112: 89-113.

Ansorena E, Garcia-Trevijano ER, Martinez-Chantar ML, Huang ZZ, Chen L, Mato JM et al. S-adenosylmethionine and methylthioadenosine are antiapoptotic in cultured rat hepatocytes but proapoptotic in human hepatoma cells. Hepatology 2002; 35(2): 274-80.

Pascale RM, Simile MM, De Miglio MR, Feo F. Chemoprevention of hepato-carcinogenesis: S-adenosyl-L-methionine. Alcohol 2002; 27(3): 193-8.

Villar-Garea A, Esteller M. DNA demethylating agents and chromatin-remodelling drugs: which, how and why? Curr Drug Metab 2003; 4(1): 11-31.

Kautiainen TL, Jones PA. DNA methyltransferase levels in tumorigenic and nontumorigenic cells in culture. J Biol Chem 1986; 261: 1594-8.

el-Deiry WS, Nelkin BD, Celano P, Yen RW, Falco JP, Hamilton SR et al. High expression of the DNA methyltransferase gene characterizes human neoplastic cells and progression stages of colon cancer. Proc Natl Acad Sci USA 1991; 88: 3470-4.


Most read articles by the same author(s)

1 2 3 > >>