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

Abstract

Genomic instability (GI) is a hallmark of many cancers. GI is believed toconfer upon impending neoplastic cells the ability to accumulate all of therequisite mutations for transformation within the relatively short time-frame of anorganism’s lifespan. Recently described properties of the c-Myc oncoproteinshow that, in addition to its directly transforming role, it can mediate GI via theinduction of reactive oxygen species and by promoting whole chromosomeinstability leading to tetraploidy and aneuploidy. Mediators of both propertieshave been identified and have begun to provide a framework within which tounderstand not only how c-Myc alters the genome but how it might alsocooperate with its more traditional transforming activities. These genome-alteringproperties of c-Myc suggest that they provide the protein with the ability to confera “mutator phenotype” to cells in which its expression is de-regulated.