DNA METHYLTRANSFERASE 1 (DNMT1) GENE ACTIVITY IN HUMAN LYMPHOMAS CORRELATES WITH ABERRANT p53 GENE EXPRESSION
Abstract
Background: The DNA Methyltransferase 1 (DNMT1) gene has been implicated as a mutagenfor tumor suppressor genes by causing hypermethylation and subsequent TA mutations of CpGislands located in the promoter regions of these genes. The present study was undertaken todetermine if increased DNMT1 gene activity correlated with increased aberrant p53 geneexpression in human lymphomas. Methods: The study was undertaken on randomly selectedarchival human lymph nodes comprising 50 normal or reactive lymph nodes and 50 lymphomalymph nodes. These were subjected to Fluorescent In Situ Hybridization (FISH) usingoligonucleotide Antisense probes for the DNMT1 and the p53 mRNA according to standard FISHprotocols. Percent cells stained, mean ‘dots’ stained per cell and staining signal intensity weretaken as the criteria for comparing control and lymphoma lymph nodes. Quantitation of probesignals was done both by manual visualization of fluorescent signals and computer based imageanalysis. Correlation analysis was performed by calculation of Pearson’s correlation coefficient.Results: Data indicated significantly increased expression of the DNMT1 and the p53 mRNA inlymphoma cases as compared to controls (p<0.001). Moreover significant correlation wasobtained for the expressions of these two genes in lymphomas (p<0.001), but not in control lymphnodes. Conclusion: Increased DNMT1 gene activity may contribute to increased p53 geneexpression in human lymphomas, supporting a mutagenic role for the DNMT1 gene.Key Words: Fluorescent In Situ Hybridization, p53, DNA Methyltransferases, lymphomas.References
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