Pathology and molecular mechanisms of hereditary gastrointestinal cancer

This thesis attempts to shed light on different hereditary CRC syndromes (Lynch, FAP, PJS) where different genetic defects in the germline lead to tumor development. From a clinical point of view, we contributed to better diagnostics of Lynch syndrome. From a basic fundamental view, we provided evidence that sulindac affects stem cell behavior in FAP patients; we also showed that CIN plays an independent role in tumor formation in a mouse model of FAP. By using organoids, the role of LKB1 in epithelial cells was explored and potential mechanisms behind the tumorigenesis of PJS syndrome could be suggested. Our findings cover a broad range from fundamental to translational research and clinical practice and they further improve our understanding of the molecular basis of hereditary colorectal tumorigenesis.