The initiating lesion, by definition, will be present in all the tumor cells, and therefore cannot increase at the same magnitude as later mutations.
The implication of this is that the inactivating mutations occur at an appreciable rate, but the fraction of mitochondrial genomes per cell carrying these variants cannot increase beyond a certain limit without impairing the selective fitness of that cell.
The T1127M mutation is able to rescue the dendritic arbor phenotype but not the spine volume and also cannot increase spine volume when overexpressed.
When chaperone becomes scarce, either because of increased need due to stress or due to a mutation in a chaperone, the accumulated destabilizing mutations cannot be buffered and the malfunctioning of proteins manifests in the mutant phenotype.
Subsidizing low budget buyers cannot increase revenue.
"We cannot increase the quotas before December".
The participant believes that mutations cannot be constructive (useful).
At least, it cannot increase oil prices.
This means that these two mutations cannot complement each other.
Those mutations cannot be detected with focus techniques.
