The CMS2 subtype corresponds to the canonical subtype (37% of CRCs) and is characterized by CIN-high, microsatellite stability (MSS) and low levels of gene hypermethylation; a mutational profile typically observed in CIN-high CRCs, including recurrent APC (75%), TP53 (70%), and KRAS (30%) mutations, whereas BRAF mutations were absent; pronounced upregulation of WNT and MYC downstream targets, elevated expression of EGFR, HER2, IGF2, IRS2, HNF4A, and cyclin; complex tubular histological structure, predominantly located in the distal region of the colon. Here, IRS2 is linked to cervical squamous intraepithelial neoplasia.