Moreover, the overrepresentation of mutations in the cohort of women with contralateral breast cancer is important to the clinical management of women carrying PALB2 mutation as it implies a significant risk of developing a second primary breast neoplasm [ 84].
Finally, the overrepresentation of double mutations among those genotypes that lost the AND function is interesting its own right, because it implies that the component mutations were not beneficial when they arose individually in the +EQU/-AND environment.
If this is true, it implies that the mutation rate for the first cell division might have been underestimated.
The excess of short deletion over short insertion mutations implies that indel mutations of these lengths should lead to a loss of approximately 0.30 nt per single-nucleotide replacement.
The fact that truncating mutations and early nonsense mutations cause RTT implies that the disease is typically caused by loss of function of MeCP2.
In conclusion, the presence of a different spectrum of secondary rifabutin mutations implies that either, the mutation rate of individual mutations has changed, due to a defect in DNA repair or replication, or that additional spontaneous mutations are viable (and lead to resistance) in the presence of the S522L mutation [ 2].
For example, despite the mutually exclusive nature of K27M and G34 mutations, which implies a common pathway or biological process, there are important differences.
Woodruff et al. [ 35] approached the issue of "clustered mutations", which implies that related individuals may inherit identical genetic changes, contrasting an assumption that mutations are independent events.
Thus, the local duplicate has a higher chance of being removed through accumulation of degenerative mutations, which implies a higher level of Ka/Ks.
Our observation that ΔN-Bcat expression co-operates functionally with loss-of-function mutations in Apc rather than gain-of-function Kras mutations implies the existence of a minimal threshold level for canonical Wnt/β-catenin signaling to trigger tumor formation (Roose et al., 1999; Samuel et al., 2009; Albuquerque et al., 2010; Buchert et al., 2010; Leedham et al., 2013).
