Frameshift mutations are particularly common in colorectal cancer with high microsatellite instability, leading to dysregulated RNA methylation and altered cancer cell phenotypes (Fig. 2).67, 68, 69 In colorectal cancer with high microsatellite instability, inactivating mutations in methyltransferase genes like METTL16 disrupt RNA methylation, resulting in the loss of protein function. Here, METTL16 is linked to cancer.