AB039. SOH23ABS_198. MLH1-deficient colorectal carcinoma with wild type BRAF and MLH1 promoter hypermethylation—an understudied molecular phenotype

Background: Up to 15% of colorectal cancers (CRCs) display microsatellite instability (MSI). MSI is reflective of a deficient mismatch repair (MMR) system (dMMR). dMMR CRC represents a heterogeneous group of diseases with separate tumorigenic pathways. The majority of dMMR CRC is sporadic (>90%) and occurs due to acquired methylation of the MLH1 gene promoter. Sporadic MLH1-deficient CRC is thought to originate in lesions that arise from the serrated neoplasia pathway. Although the presence of the BRAF V600E mutation is characteristic of a sporadic cancer, as many as half of CRCs with MLH1 promoter hypermethylation will lack a BRAF mutation.