Oncogene mutations as intermediate markers.

Tumors arise through a series of genetic changes which include activation of protoocogenes and inactivation of tumor suppressor genes. It is now possible to identify rare cells containing genetic mutations in an excess background of normal cells. Theoretically, the identification of a clonal population of cells sharing an early genetic marker for malignant transformation would lead to valuable intermediate endpoints and could diagnose premalignant lesions amenable to chemoprevention. Ideally, these genetic changes would be specific point mutations that occur early in the tumor cascade, prior to the development of a clinically significant tumor. To identify these markers, precise histopathologic and genetic tumor models must be described. Early candidate markers include p53 point mutations in squamous cell carcinoma of the aerodigestive tract.