Molecular events in lung cancer.

The observation that genes contributing to the process of malignant transformation are altered forms of genes normally present in eukaryotic cells initiated many of the advances that have increased our understanding of lung carcinogenesis at the molecular level. The gene families implicated in carcinogenesis include dominant oncogenes and tumor suppressor genes. Proto-oncogenes (normal homologue of the oncogene) participate in critical cell functions, including signal transduction and transcription. Only a single mutant allele is required for malignant transformation. Primary modifications in the dominant oncogenes that confer gain of transforming function include point mutations, amplification, translocations, and rearrangements. A second recently described gene family is the tumor suppressor genes. Tumor suppressor genes appear to require homozygous loss of function either by mutation, deletion, or a combination of these. Some tumor suppressor genes appear to play a role in the governance of proliferation by regulation of transcription. The identification of specific genes that contribute to the development of the cancer cell presents an opportunity to use these genes and their products as prevention and treatment targets.