Mutations in PRMT family genes arising in human cancers

We analyzed mutations arising in cancer cells in nine Protein Arginine Methyltransferases (PRMT1-9) reported on the Catalogue of Somatic Mutations in Cancer (COSMIC). Most mutations are single amino acid substitutions. Consistent with this interpretation, and as previously reported, most PRMT genes are over-expressed in cancer cells. We used the CHASMPlus and VEST4 algorithms to classify mutations as either driver (probability of causing cancer) or pathogenic (probability of causing any disease), respectively. Driver mutations are virtually non-existent in any of the PRMT genes, which was not unexpected because none of the genes are classified as a driver by OncoGenomics. Pathogenic mutations were identified in six genes. We used in silico structural analysis to analyze high-frequency mutations and found that PRMT6 mutations strongly affected protein structure, whereas PRMT1 mutations tended to not impact the structure. Mutation co-occurrence between the PRMT genes is likely except between PRMT5 and PRMT6 suggesting that cells can largely tolerate mutations in more than one PRMT. Although the study presented here uses in silico analysis to catalogue PRMT1-9 mutations, it highlights interesting trends that may require further experimental analysis.