TMB is defined as the number of mutations per megabase of DNA (Mut/Mb), and in CRC it is typically increased in case of microsatellite instability (MSI) or pathogenic mutations occurring in the proofreading domains of the DNA polymerases POLE and POLD, leading to a consequential increase of tumour neoantigens (TNA) likely driving response to immune checkpoint blockade [99]. This evidence concerns the gene POLE and neoplasm.