The large deletion in the MLH1 gene, a del5-6, has not been reported in other populations and, as a single mutation, represents only 6.7% (1 of 15) of all MLH1 mutations, while LGRs in the MSH2 gene account for 50% (6 of 12) of all MSH2 mutation-positive cases [ 30- 32] (one family with inherited MSH6 mutation is unpublished).
However, how much extent these genes affect tumorigenicity, tumor progression, and resistance to EGFR-TKIs is difficult to assess, as some mutations may represent only passive alterations (passenger mutations).
These results confirm the hypothesis that recurrent somatic mutations, which represent only 1.7% of the whole PanCancer mutations, still retain meaningful information about the mutation profile of each cancer type that allows us to cluster them according to their similarity.
The absence of a clear association of p53 alterations with patient outcome may reflect the underlying complexities, and mutations may represent only a subset of the functional p53 alterations.
To date, the clinical manifestations of COL4A1 mutations in patients represent only a subset of the phenotypes observed in mice with Col4a1 mutations.
The absence of a clear association between TP53 alterations and outcome may reflect the complexity that underlies response to therapy or may be an indication that mutations in the coding sequence represent only a subset of the functional p53 alterations.
Current technologies are sensitive enough to detect tumor-specific somatic mutations, even if the ctDNA fragments represent only a minority of all DNA fragments in the circulation.
Current NGS technologies are sensitive enough to detect tumor-specific somatic mutations, even if the ctDNA fragments represent only a minority of all DNA fragments in the circulation.
In addition the Sequenom platform is more sensitive than Sanger sequencing in that it was able to detect mutations that represented only 5% of the DNA.
With respect to this, results of the preliminary studies presented in sections 'Structural-based viewpoint analysis', 'Mutation-based viewpoint analysis' and 'Reuse-centred viewpoint analysis' represent only initial evaluation stage.
