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Objective To identify potential target genes for isocitrate dehydrogenase (IDH) mutations in cholangiocarcinoma. Methods DNA methylation 450K data and mRNA expression data of the TCGA CHOL project were downloaded. Probe-wise differential methylation analysis and differential expression analysis were performed through limma and DESeq2 in the IDH-mutant vs IDH-WT comparison. Then, Spearman correlation analysis was performed between the normalized expression levels of differentially expressed genes and the methylation levels of corresponding differentially methylated sites. Genes with high methylation, low expression, and strong negative correlation were screened for enrichment analysis to explore their functions. A protein interaction network was constructed and the core modules were found by MCODE. Results The analysis revealed 11 605 differentially methylated sites, of which 10 427 were hypermethylated; and 651 of the 735 differentially expressed genes were down-regulated. Among them, 143 down-regulated genes and 328 hypermethylation sites formed 330 strongly negatively correlated combinations. The above 143 genes are enriched in the regulation of epidermal growth factor receptor signaling pathway, cell extravasation and cell division. By constructing a protein-protein interaction (PPI) network, 10 genes of its core module were identified, which were involved in biological processes such as epithelial cell differentiation and development, and cellular protein localization. Conclusions By integrating the TCGA cholangiocarcinoma transcriptome and DNA methylation data, the potential target genes for IDH mutations are obtained and the core modules of their PPI network are identified, providing new clues for the role of IDH mutations in the development of cholangiocarcinoma.