Epigenetic profiling of oral cancer

Oral squamous cell carcinoma (OSCC) is the most common type of oral neoplasm,accounting for over 90% of all mouth malignancies and 38% of head and neck tumors.Worldwide, OSCC is the eighth most common human cancer, with more than 500,000 newcases being diagnosed every year. Surprisingly, the number of annual deaths for this diseasehas practically not changed in the last 30 years (Funk, G.F.; Karnell, L.H., 2002).This is because invasive surgical treatments (involving both oral cavity and neck) are stillthe only effective way to treat OSCC; thus detection in early stages could dramaticallyimprove cure rates and quality of life by minimizing invasive surgery (Scully, C., 1995). Toimprove diagnosis and prevention, researchers have spent considerable effort to understandwhich genetic and/or environmental changes may be related to this tumor. Althoughenvironmental risk factors associated with development of oral cancer have been sufficientlyunderstood (smoking, alcohol, betel, diet, living habits, etc.), knowledge of the genetic basesin oral carcinogenesis is still a challenging task. OSCC is a result of multiple genesalterations, which are modulated by individual predisposing conditions and environmentalinfluences. Furthermore, in the last ten years a new category of non-genetic events able tomodify gene expression has been massively investigated: the so called ‘epigeneticphenomena’ (Bird, A., 2007).Epigenetic factors are non-genetic phenomena which interfere with genes expression. Suchmodifications pass on successive generations of cells, even if there is no mutation incorresponding genes. Epigenetic events are linked with carcinogenesis when one or more oncogenes/tumour suppressors are directly or indirectly affected such that their expressionand function may be permanently altered (Feinberg, A.P., 2001)Cellular aging, risk factors and, as recently discovered, chronic inflammation via mediators,such as IL-6, may be potential inducers of epigenetic alterations in oral mucosa cells. It is ageneral belief that these alterations would accumulate in the normal-appearing mucosawhile carcinogenesis is in progress, or before any tumor lesion is detected.Three major types of such epigenetic mechanism are currently known: DNA hyper-methylation, histone code changes and RNA interference.