Genetic control and molecular mechanisms in malignant, inflammatory and developmental pathologies of the orofacial region

A comprehensive analysis of alterations at the molecular level occurring during malignant transformation of epithelial cells (squamous and basal) in the orofacial region is the main aim of this project. Mutation screening in cancer genes will be done in all stages of tumour development -from premalignant to fully developed malignant phenotype, including metastasis. Association studies on genetic polymorphisms in different gene families performed on patients and healthy individuals will be carried out in order to estimate the risk for developing squamous cell carcinomas (SCC) or basal cell carcinomas (BCC). In gene expression studies, emphasis will be placed on cell proliferation and cell death mechanisms and on several crucial signaling pathways (Ras, p53, Shh), with the ultimate goal to better understand the complex signaling network involved in the pathogenesis of orofacial tumours, and to identify novel prognostic markers. Infection and inflammation may be etiological factors in cancer, but may also be its consequence. Namely, cancer patients are often immunocompromised and easily develop infections. We plan to establish the microbiological status of the patients and assess the significance of this finding. Finally, since neoplastic transformation and development have some molecular pathways in common, an aspect of this connection will be addressed through genetic analysis of common orofacial developmental anomalies- cleft lip and palate.