PubMed1993
Due to a variety of known and unknown control mechanisms, the human genome is remarkably stable when compared to most other species. The long latency periods of most solid tumors, during which the cell undergoes malignant transformation, are presumably due to this stability. The molecular basis responsible for the induction of genetic instability and the resultant biological characteristics manifest in tumor populations is not well understood. The discovery of both oncogenes and tumor suppressor genes, however, has placed the phenomenon of human genome stability on a more solid conceptual footing. These types of genes clearly place multiple barriers to oncogenic transformation, and traversing these barriers apparently requires both time and the accumulation of genetic defects that cannot be corrected. The evolution of neoplasias can, therefore, be predicted to be due to: (1) consistent and progressive loss of tumor suppressor genes; (2) gene amplification, resulting in the over-expression of proteins that aid in tumor progression; (3) gene mutation, which alters the orderly biochemistry of the normal cell; (4) genes that allow a cell like the melanocyte to escape the confining nature of the epidermis and to invade through the dermis into the circulatory and lymphatic systems in order to disseminate itself to other organs (e.g., proteolytic enzymes, enzyme inhibitors, integrins, metastases genes, chemotactic factors etc.); (5) factors, perhaps such as TGF beta 2, that may impact negatively on MHC antigens and confuse host defense mechanisms; and (6) S.O.S.-type genes, which may be expressed as a direct response to the accumulating damage in an attempt to correct the damage, but that may then become part of the problem instead of the solution. The extraordinary plasticity and instability of the genome of a melanoma cell suggests an inordinate amount of genetic flux. In addition to activating and inactivating various genes, this constant shuffling and rearranging of the genome in neoplasms such as MM may be constantly altering gene dose. Cytogenetic and molecular biological studies have been the Rosetta stone for understanding the etiological relevant genetic events in human cancers. Genetic alterations fundamental to the pathology of MM have begun to be defined. Studies designed to understand these perturbations at the biochemical and organismic level are underway.(ABSTRACT TRUNCATED AT 400 WORDS)
Cell Transformation, Neoplastic↗