Am J Blood Res 2012;2(3):160-169
Review Article
Unbalanced replication as a major source of genetic instability in cancer cells
Daniel Corcos
INSERM U955- Hôpital Henri Mondor, 51 Avenue du Maréchal de Lattre de Tassigny, Faculté de Médecine-Paris 12, Créteil
94010
Received July 18, 2012; accepted August 30, 2012; Epub October 20, 2012; Published October 30, 2012
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. (AJBR1207003).
Keywords: Genetic instability, tumorigenesis, oncogenes, tumor suppressor genes, DNA replication, cell replication,
replication unbalance, chromosomal instability
Address all correspondence to:
Dr. Daniel Corcos, INSERM U955- Hôpital Henri Mondor, 51 Avenue du Maréchal de Lattre de Tassigny, Faculté de
Médecine-Paris 12, Créteil 94010. E-mail: daniel.corcos@inserm.fr
Review Article
Unbalanced replication as a major source of genetic instability in cancer cells
Daniel Corcos
INSERM U955- Hôpital Henri Mondor, 51 Avenue du Maréchal de Lattre de Tassigny, Faculté de Médecine-Paris 12, Créteil
94010
Received July 18, 2012; accepted August 30, 2012; Epub October 20, 2012; Published October 30, 2012
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. (AJBR1207003).
Keywords: Genetic instability, tumorigenesis, oncogenes, tumor suppressor genes, DNA replication, cell replication,
replication unbalance, chromosomal instability
Address all correspondence to:
Dr. Daniel Corcos, INSERM U955- Hôpital Henri Mondor, 51 Avenue du Maréchal de Lattre de Tassigny, Faculté de
Médecine-Paris 12, Créteil 94010. E-mail: daniel.corcos@inserm.fr
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