The identification of the 3 major IDH1/2 mutations showed very high sensitivity levels, respectively 0.8% for IDH1 R1.2H, 1.2% for IDH1 R132C and 0.6% for IDH2 R172K.
In addition, serum from a cohort of individuals with Growth Hormone Receptor (GHR) mutations, showing very low cancer and diabetes incidence, inhibited the expression of N-Ras, TOR and PKA when added to cultured primary human epithelial cells [ 35].
The A86G mutation shows very low activity and the C and U mutations are totally inactive.
hMLH1-deficient cell lines due to either epigenetic silencing or mutation showed very similar IC50 and were four- to nine-fold more sensitive to CPT-11 than the MSS line.
Interestingly, DRG sensory neurons expressing the K141N-HSPB8 did not exhibited any obvious morphological phenotype, whereas the K141E-HSPB8 mutation showed very mild neurite degeneration with only 10% of the neurites being affected.
In addition, eight mutations that show very fast kpep values and thus suppress the effect of the hyperstable Tyr-T1 tRNATyr are all proteins that substantially weaken binding to aa-tRNA (ΔΔ Go > 0.6 kcal/mol).
Thus, markers that differ substantially in their mutation rates can show very different patterns of molecular diversity, as we found in our case.
