[Molecular basis of cancer]

Cancer is a group of diseases characterized by an autonomous proliferation of neoplastic cells which have a number of alterations, including mutations and genetic instability. Cellular functions are controlled by proteins, and because these proteins are encoded by DNA organized into genes, molecular studies have shown that cancer is a paradigm of acquired genetic disease. The process of protein production involves a cascade of several different steps, each with its attendant enzymes, which are also encoded by DNA and regulated by other proteins. Most steps in the process can be affected, eventually leading to an alteration in the amount or structure of proteins, which in turn affects cellular function. However, whereas cellular function may be altered by disturbance of one gene, malignant transformation is thought to require two or more abnormalities occurring in the same cell. Although there are mechanisms responsible for DNA maintenance and repair, the basic structure of DNA and the order of the nucleotide bases can be mutated. These mutations can be inherited or can occur sporadically, and can be present in all cells or only in the tumor cells. At the nucleotide level, these mutations can be substitutions, additions or deletions. Several of the oncogenes discussed below, including the p53, c-fms, and Ras genes, can be activated by point mutations that lead to aminoacid substitution in critical portions of the protein. This article examines the current concepts relating to cellular mechanism that underlie the molecular alterations that characterize the development of cancer.