EPITHELIAL CELL COMPETITION IN THE EARLY STAGES OF ORAL SQUAMOUS CELL CARCINOMA
Previous studies have unveiled key genomic alterations found in late-stage OSCC, when tumors are already formed, leveraging our understanding of genes that, once mutated, may contribute to OSCC development. However, the mutational landscape of human normal oral epithelia, as well as of early lesions, remains largely uncharacterized. Furthermore, whether cell competition plays a role in the selection of driver mutations as OSCC unfolds remains to be determined. NOTCH1 has long been regarded as a tumor suppressor gene found to be frequently mutated in HNSCC, but the frequency of NOTCH1 inactivating mutations in human normal oral epithelia and its implications for OSCC development remain to be disclosed. To address these questions, my project will be based on the investigation of the somatic mutational landscape of normal oral epithelia and the role of NOTCH1 inactivation and cell competition in OSCC development. A combination of 3D in vitro primary culture and in vivo mutant reporter mice will be used, and focus will be put on buccal mucosa and tongue epithelium, two of the most affected regions in OSCC.
Previous studies have unveiled key genomic alterations found in late-stage OSCC, when tumors are already formed, leveraging our understanding of genes that, once mutated, may contribute to OSCC development. However, the mutational landscape of human normal oral epithelia, as well as of early lesions, remains largely uncharacterized. Furthermore, whether cell competition plays a role in the selection of driver mutations as OSCC unfolds remains to be determined. NOTCH1 has long been regarded as a tumor suppressor gene found to be frequently mutated in HNSCC, but the frequency of NOTCH1 inactivating mutations in human normal oral epithelia and its implications for OSCC development remain to be disclosed. To address these questions, my project will be based on the investigation of the somatic mutational landscape of normal oral epithelia and the role of NOTCH1 inactivation and cell competition in OSCC development. A combination of 3D in vitro primary culture and in vivo mutant reporter mice will be used, and focus will be put on buccal mucosa and tongue epithelium, two of the most affected regions in OSCC.