title: Unbalanced replication as a major source of genetic instability in cancer cells.
abstract: The origin of genetic instability in tumors is a matter of debate: while the prevailing model postulates a mutator phenotype resulting from an alteration in a caretaker gene as a prerequisite for genetic alterations leading to tumor formation, there is evidence against this model in the majority of cancers. A model for chromosomal instability should take into account the role of oncogenes in directly stimulating DNA and cellular component replication, creating aberrant structures when overexpressed. I will distinguish here two distinct mechanisms for the genetic instability of tumors: primary and secondary. Primary genetic instability is dependent on the inactivation of genes involved in maintaining genetic stability (caretaker genes), whereas secondary genetic instability is dependent on genes involved in tumor progression, i.e. oncogenes and tumor suppressor genes of the gatekeeper type. Secondary genetic instability, the most frequent condition, can be explained by the fact that some of the genes involved in tumor progression control replication of cell structures from within, leading to replication unbalance.
authors.affiliation: INSERM U955- Hôpital Henri Mondor 51 Avenue du Maréchal de Lattre de Tassigny, Faculté de Médecine, Paris 12, Créteil 94010.
authors.forename: Daniel
authors.initials: D
authors.lastname: Corcos
keywords: DNA replication; Genetic instability; cell replication; chromosomal instability; oncogenes; replication unbalance; tumor suppressor genes; tumorigenesis