Integrated analysis of genome-wide gene expression and DNA methylation microarray of Diffuse large B-cell lymphoma with TET mutations

Abstract

Diffuse large B-cell lymphoma (DLBCL), the most frequently occurring type of lymphoid malignancy, has been demonstrated to be associated with mutations of Ten-Eleven Translocation (TET). In order to explore the association between DLBCL and TET mutations, the present study analyzed the gene expression and methylation profles in human DLBCL biopsy tissues with wildtype and mutated TET2. The microarray dataset GSE37365, containing two subseries: the genome-wide gene expression dataset GSE37362 and the DNA methylation microarray dataset GSE37363, was downloaded from the Gene Expression Omnibus database. Differentially expressed genes (DEGs) were identified using the limma package of R. Furthermore, differentially methylated sites and differentially methylated regions were identified. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses were performed via GO stats and GSEABase packages respectively. Finally, the Pathview package was used to construct the network of enriched pathways. A total of 198 DEGs (106 up- and 92 downregulated) were obtained. A total of 602 shared differentially methylated genes (DMGs) were identified according to differentially methylated levels. A total of 12 overlapping genes were identified in DEGs and DMGs. It was observed that 9 of the 12 overlapped genes were downregulated and hypermethylated, with 24 GO terms and one KEG G pathway sign ifica ntly en r iched. The results of the present study demonstrated that the genes cryptochrome circadian clock 1, zinc finger protein (ZNF) interacting with K protein 1, ZNF134, ZNF256 and ZNF615, which were hypermethylated and downregulated in DLBCL patients with TET2 mutations, were the key genes in the association between DLBCL and TET mutations. These genes may act as potential biomarkers for the diagnosis of DLBCL in the future.