Genetics deletion mutation

On pharmacodynamic grounds, tumor resistance may be caused by such diverse mechanisms as the mutation or redundancy of topo II, the overexpression and preferred nuclear localization of proteasome a-type subunits (leading to a anomalous degradation of topo II), genetic deletion or loss-of-function mutations of p53, overexpression of ROS-detoxifying enzymes, overexpression of Bcl-2 (leading to a diminished cyt c release), etc. However, none of these factors would universally predict the development of anthracycline-resistance in a given tumor or another. 

These genetic tests enable one to resolve the overall induction curve for purple colonies (presumptive ad-3 mutants) into its individual components point mutations at the ad-3 A and ad-3B loci and chromosome-deletion mutations covering each locus individually as well as both loci simultaneously. 

Somatic mutation theories (2,3,10-15) postulate that the origin of diversity is a normal genetic event (mutation, deletion, insertion or recombination) which occurs in V genes at low frequency throughout the life of the individual. We will first consider mechanisms that do not involve recombination. 

Bua E, Johnson J, Herbst A et al. (2006) Mitochondrial DNA-deletion mutation accumulate intracellularly to detrimental levels in aged human skeletal muscle fibers. Am J Him Genet 79, 469 80. 

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