The mutations observed in this study are mainly transition missense base changes, as previously described [ 8, 9, 23].
Mutations were identified in the matched samples, with similar ratios of transitions and missense changes between cell lines and tissues.
This analysis uncovered three further C G → T A or G C → A T transitions (2 missense and 1 silent) at CpG dinucleotides in MLH1 and MSH6 (Table 1).
A nonmonotonic pattern of change is evident and trend tests failed to confirm a significant increase in median frequencies over time in any polymorphism class (P > 0.10 for all comparisons: Jonckheere Terpstra test; transitions, transversions, missense, and silent changes: 2520, 19,896, 18,472, and 4568 observations, respectively).
In our study, the only type of K-RAS mutation, which has been associated to adverse outcome, was G>A transition resulting in missense mutations (Gly>Ser or Gly>Asp).
Mutant 1 (Mut-1, missense mRNA) contains the G>A transition and is expected to produce a full-length 150-kDa E264K mutant protein.
MutSigCV computes the statistic for different classifications of mutations (transitions, transversions, nonsense, missense, etc)., then combines these different statistics to compute an overall P value of significance that each gene is frequently mutated in the patient cohort, assuming a beta-binomial null distribution.
The A- variant differs from the normal G6PD B allele by two missense mutations, an A to G transition at position 376, encoding the so called "B" to "A" change (Asn126Asp), and a G to A transition at position 202, encoding the "A-" change (Val68Met).
Mutation probabilities thus derived were grouped into pairs of vectors according to types of polymorphism: transitions versus transversions or missense versus silent changes.
For significant polymorphisms, FDR probabilities were calculated across pairs of mutation types: across transitions and transversions or across missense and silent changes.
