In colorectal cancer (CRC), several findings associated DOT1L and its histone modifications with crucial steps of carcinogenesis, including transcriptional regulation of tumor suppressor genes (TSGs) (Jacinto et al., 2009), stemness (Kryczek et al., 2014; Lv et al., 2019), Wnt signaling pathway (Mahmoudi et al., 2010; Gibbons et al., 2015), cell cycle progression (Yang et al., 2019), tumor invasiveness (Liu et al., 2020), and DNA damage response (Kari et al., 2019) genes. The gene discussed is DOT1L; the disease is colorectal carcinoma.