Of note, the CMS classification only considers a fraction of genomic variations, such as BRAF, TP53, and KRAS mutations, HNF4A amplification, and homozygous deletion of PTEN, but there is a wide range of genomic variations in CRC (6–13); thus, the genomic variations considered in the CMS classification system cannot fully explain the molecular heterogeneity of CRC, and the CMS classification system might ignore a large number of potential therapeutic targets and genomic drivers. The gene discussed is HNF4A; the disease is colorectal carcinoma.