[Genome instability and oncogenesis]

Abstract

Molecular alterations leading to genetic instability play a key role in tumor development. The basic reasons of genetic instability of tumor cells, i.e. up-regulation of intracellular level of endogenous mutagens, in particular reactive oxygen spesies (ROS); decreased fidelity of DNA replication and chromosome segregation in mitosis; defects in DNA repair systems; and inactivation of cell cycle checkpoints preventing proliferation of abnormal cells are reviewed. In addition, tissue-specificity of tumorigenesis connected with genetic instability and development of new therapeutic approaches based on diminishing genetic instability or selective killing of neoplastic cells showing such defects are discussed.