Genetic mechanisms of solid tumor oncogenesis.

The study of the genetic alterations of tumor suppressor genes and protooncogenes in solid tumors has greatly increased our understanding of cancer biology. These findings have extended epidemiologic associations of carcinogens with certain tumors. Further analysis of patterns of genetic changes may implicate carcinogenic substances in cases where epidemiology has not been able to do so. Identification of germline mutations in p53, APC, and NF1 has provided improved diagnosis and presymptomatic screening in cancer kindreds. The identification of additional alterations in tumor suppressor genes may further improve the ability to predict inherent cancer risk. Screening strategies based on detection of genetic abnormalities of preinvasive cancerous lesions, such as mutant ras in colonic polyps, may improve early diagnosis. Finally, strategies to replace lost tumor suppressor function may provide a future therapeutic modality.