The role of recurrent somatic mutations that alter conserved mA motifs in human cancer.

N-methyladenosine (mA) is the most abundant internal RNA modification in eukaryotes and plays a key role in cellular growth and development. Global changes in cellular methylated RNA and mA-mediated transcript regulation significantly impact oncogenesis. Here, we investigate how recurrent synonymous and non-synonymous somatic mutations abolishing individual canonical methylated mA motifs affect transcript levels and survival of patients with cancer. Moreover, we explore the effect of these mutations on creating mA motifs. To this end, we compared publicly available data on mA sites with mutations reported in The Cancer Genome Atlas (TCGA). We find that mutations disrupting or creating mA motifs display a low recurrence and have a negligible impact on RNA abundance. Patients with the highest number of disrupted mA sites or newly generated mA motifs did not generally exhibit alterations in mortality risk or outcomes. Hence, our data suggest that mutational alterations in the mA motif landscape are unlikely to be a primary mechanism for regulating gene function across most cancer types. This may be attributed to the fact that mutations typically affect individual mA sites, which is likely insufficient to significantly impact gene expression.