The main etiological factor for oral squamous cell carcinoma (OSCC) is tobacco use; however nonsmoking cases have also been reported. The molecular basis of emerging oral malignancy in non-smokers is poorly understood. We seek to profile the microRNA patterns in this subset of patients. Methods: We evaluated global microRNA expression in multiple biopsies representing varied stages of oral cancer/pre-cancer taken from a single, contiguous field of diseased oral tissue. Results: We find distinct

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... lists of frequently deregulated microRNA in each field. MiR-155 was selected for further validation in an independent cohort comprised of tissues from smokers and non-smokers. Highly expressed miR-155 was identified in 58% of OSCC cases and 83% of dysplasia cases. Conclusions: We conclude that miR-155 may be a driver of oral tumorigenesis and that molecular heterogeneity across fields of diseased tissue has significant implications when selecting candidates for development of targeted therapies.