The Ever Expanding Role for c-Myc in Promoting Genomic Instability

Genomic instability (GI) is a hallmark of many cancers. GI is believed to confer upon impending neoplastic cells the ability to accumulate all of the requisite mutations for transformation within the relatively short time-frame of an organism's lifespan. Recently described properties of the c-Myc oncoprotein show that, in addition to its directly transforming role, it can mediate GI via the induction of reactive oxygen species and by promoting whole chromosome instability leading to tetraploidy and aneuploidy. Mediators of both properties have been identified and have begun to provide a framework within which to understand not only how c-Myc alters the genome but how it might also cooperate with its more traditional transforming activities. These genome-altering properties of c-Myc suggest that they provide the protein with the ability to confer a "mutator phenotype" to cells in which its expression is deregulated.