Assessing ‘field cancerization’ in a colonic stem cell mismatch repair in vivo model of Lynch syndrome

Dr. Montoya-Uribe’s research focuses on elucidating the mechanisms underlying the pathogenesis of Lynch syndrome in response to pro-inflammatory diets. Lynch Syndrome is one of the most common causes of hereditary colorectal cancer (CRC) that affects approximately 30 million people around the world. Lynch Syndrome patients have germline mutations in genes that regulate cellular DNA mismatch repair (MMR) in the body. However, the mechanisms underlying the pathogenesis of CRC in Lynch Syndrome have not been elucidated. Thus, Dr. Montoya-Uribe tracked the fate of DNA mismatch repair deficient-colonic stem cells lineages in mice fed a high-fat diet during the initial stages of CRC. Her novel findings demonstrate for the first time that MMR-deficient colonic stem cells have a selective advantage (compared to normal wildtype) and clonally expand over time.  We propose that MMR-deficient crypts drive cancer initiation.