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Background  5-Methylcytosine (m 5 C) is a reversible modification to both DNA and various cellular RNAs. However, its roles in developing human cancers are poorly understood, including the effects of mutant m 5 C regulators and the outcomes of modified nucleobases in RNAs.    Methods  Based on The Cancer Genome Atlas (TCGA) database, we uncovered that mutations and copy number variations (CNVs) of m 5 C regulatory genes were significantly correlated across many cancer types. We then assessed the correlation between the expression of individual m 5 C regulators and the activity of related hallmark pathways of cancers.    Results  After validating m 5 C regulators’ expression based on their contributions to cancer development and progression, we observed their upregulation within tumor-specific processes. Notably, our research connected aberrant alterations to m 5 C regulatory genes with poor clinical outcomes among various tumors that may drive cancer pathogenesis and/or survival.    Conclusion  Our results offered strong evidence and clinical implications for the involvement of m 5 C regulators.    Supplementary Information  The online version contains supplementary material available at 10.1186/s12957-021-02342-y.

Pan-cancer analysis of m5C regulator genes reveals consistent epigenetic landscape changes in multiple cancers