Dietmaier et al., "Aspirin suppresses the mutator phenotype
associated with hereditary nonpolyposis colorectal cancer by genetic selection," Proceedings of the National Acadamy of Sciences of the United States of America, vol.
On the other hand, most mutations demonstrate an UV-signature and one might speculate that a cancer driven mostly by exogenous UV-induced mutations might be less prone to acquire the additional mutations necessary for the metastatic process than a cancer evolving primarily through a mutator phenotype
or through marked aneuploidy.
Identification of an even growing number of guide genes and target genes of the mutator phenotype can lead to discover new complex molecular mechanisms that underlie the process of colorectal tumorigenesis .
This concept is also partially extended to other minor MMR genes; overexpression of the MSH3 gene in cultured mammalian cells selectively inactivates MutS[alpha] because MSH2 is sequestered into a MSH2-MSH3 (MutS[beta]) complex, resulting in reduced MutS[alpha]-dependent repair of base-base mismatches and a strong base substitution mutator phenotype .
Mutations of the mitochondrial polymerase gamma cause a mitochondrial DNA (mtDNA) mutator phenotype
which in mice has been correlated to premature aging and decreased lifespan [1, 2].
However, proximal tumours developed in a p53-independent manner which may indicate a preference towards the mutator phenotype
with the accumulation of mutations owing to mismatch repair deficiency.
This finding, termed microsatellite mutator phenotype
or microsatellite instability (MSI), is detectable in more than 90% of colorectal cancer specimens from patients with HNPCC and in 10% to 15% of sporadic colorectal cancer specimens.
Transient expression of a mutator phenotype
in cancer cells.
On the other hand, in Mi smegmatis, the abrogation of the Ung activity leads not only to increased mutator phenotype
but also to growth inhibition by reactive nitrogen intermediates (7).
Studies of hereditary tumors of the colorectum have identified 2 major pathways by which CRCs develop--the suppressor gene pathway and the mutator phenotype
Therefore, a mutation Gly to Arg at position 58 may have a important effect on enzyme activity and lead to a mutator phenotype
The failure to show mutator phenotypes
in Beijing/W strains suggests that this role may have been transient (10,11).