The diverse molecular profiles of lynch syndrome-associated colorectal cancers are (highly) dependent on underlying germline mismatch repair mutations

Lynch syndrome (LS) is a hereditary cancer that accounts for 3% of all new colorectal (CRC) cases. Patients carry germline pathogenic variant in one the mismatch repair (MMR) genes (MLH1, MSH2, MSH6 or PMS2), which encode proteins involved post-replicative proofreading and editing mechanism. The clinical presentation LS highly heterogeneous, showing high variability age at onset penetrance cancer, may be partly attributable to molecular profiles carcinomas. This review discusses frequency alterations WNT/B-CATENIN, RAF/MEK/ERK PI3K/PTEN/AKT pathways identified four subgroups how these changes relate ‘three pathway model’ carcinogenesis, CRCs develop from MMR-proficient adenomas, MMR-deficient adenomas directly crypts. Understanding specific differences carcinogenesis each subgroup will aid further optimization guidelines diagnosis, surveillance treatment.