Genome instability and oncogenesis

Molecular alterations leading to genome instability play a key role in tumor development. The basic causes of genetic instability of tumor cells are considered, including distorted regulation of the intracellular level of endogenous mutagens, in particular, reactive oxygen species; impaired fidelity of DNA replication and mitotic chromosome segregation; defects in DNA repair systems; and inactivation of cell-cycle checkpoints, which arrest proliferation of abnormal cells. The review discusses the causes of the tissue specificity of carcinogenesis due to genetic instability, as well as prospects of developing new means to control tumor growth via diminishing genome instability or using defects in the control of genome integrity for selective elimination of neoplastic cells.