MOLECULAR LESIONS IN HUMAN ORAL-CANCER - THE INDIAN SCENE

Carcinogenesis is a multi-step process including aberrant expression o f two interacting classes of genes oncogenes and tumour suppressor gen es. With recent technological advances, it is feasible to identify the various molecular lesions underlying the different stages of neoplasi a. Squamous cell carcinomas of the head and neck, although representin g 2-4% of the malignancies in the West, comprise a large fraction (40% ) of total cancers in India, posing a major health problem. Further, e pidemiological and experimental evidence unequivocally confirms a caus al association between tobacco chewing habit, highly prevalent in Indi a, and oral cancers. Thus, the oral cancers offer an excellent in vivo system for the study of the environmental tobacco-carcinogen induced molecular alterations in the malignancy, and associated premalignant l esions such as leukoplakia. With a view to elucidating the molecular l esions involving oncogenes in oral carcinogenesis, we have investigate d myc/ras/EGF-R activation by amplification, point mutation, gene rear rangement and allelic losses. Further, a functionally activated potent transforming gene was detected in a NIH3T3 transfection/tumorigenicit y assay, unrelated to myc/ras/EGF-R. Studies on the involvement of p53 gene in oral cancer, indicates p53 allelic loss as an event observed in leukoplakia and tumour tissues. Advanced oral cancer stages demonst rate cumulative molecular aberrations, with greater than 95% samples s howing oncogene involvement, thus indicating a multi-step process of o ral carcinogenesis. The review presents a comparative picture of the o ral malignancies seen in Western countries and India, significance of molecular lesions and future perspectives of oncogenes and tumour supp ressor gene involvement in oral cancer.