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Instability in Oncogenesis Directly Implicates Mutator Phenotype Progression through Genetic Lesion Heterogeneity

Lawrence M Agius

Theoretical uncertainties regarding the dimensions of mutator mutations are reflected particularly in the parameter uncertainties of the oncogenic pathways that are heterogeneous in individual tumor cells. The key attribute of marked heterogeneity in genomic lesions attests for the essential evolution of the mutator phenotype per se, and allows for the emergence of oncogenesis beyond initial or middle course events in malignant transformation. Although initial or early mutator mutations may prove rare events in oncogenesis, the emergence also of passenger mutations reflect an essential establishment of a mutator phenotype as essential genomic instability and mutability.