When 4 or more oncogenic mutations are required, mutator pathways predominate.
When 2 or fewer oncogenic mutations are required, non-mutator pathways predominate.
In retinoblastoma, few oncogenic mutations are required, but as the mutator mutation is also the pathognomonic oncogenic mutation, its occurrence is favored.
In general mutator pathways are favored when 5 or more oncogenic mutations are required for malignant transformation and not favored when 2 or fewer oncogenic mutations are required.
In this case, the fewer oncogenic mutations are required for increased fitness, the greater the relative predominance of this mutator pathway with late mutator mutations.
As is the case with other cancer-inducing viruses, it is likely that EBV serves as only the first step toward malignant transformation and that additional mutations are required for bringing about this process.
New drugs capable of restoring the CFTR protein damaged by the most common mutations are required.
Extensive studies have provided evidence that a series of sequential and independent mutations are required to develop the full potential of the Warburg effect [10, 24, 26].
Knowledge of protein structure, dynamics, enzyme mechanisms, and natural evolution demonstrates that multiple (combinatorial) mutations are required to discover the most improved variants.
In contrast, for hill-climb selection the rate of increase above the neutral case decreases when fewer mutations are required (Fig. 3A).
Single mutations on the helix substantially lowered IGH526 binding but did not affect neutralization, indicating either that multiple mutations are required or that additional regions are recognized by the antibody in the context of the membrane-associated envelope oligomer.
