Toni Lemmetyinen

Abstract Peutz-Jeghers syndrome (PJS) is associated with early-onset and recurring gastrointestinal hamartomatous polyposis caused by hereditary inactivating mutations in the tumor suppressor gene LKB1 (STK11). Due to lack of efficient prophylactic therapies PJS patients require regular surgical interventions and have an increased risk of cancer. LKB1-deficient fibroblasts have been identified as drivers of polyposis, but a safely druggable target remains to be identified.

Abstract Inactivating germline mutations in the tumor suppressor kinase LKB1 (STK11) predispose to Peutz-Jeghers Syndrome (PJS) with increased cancer risk and early-onset development of gastrointestinal polyps requiring regular surveillance. Studies using PJS mouse models have indicated fibroblasts as drivers of polyp formation. Here, we use single-cell RNA sequencing to investigate the fibroblast heterogeneity and tumorigenic mechanisms in a PJS mouse model.