Results To mimic human sporadic colon cancer in mice, a cDNA encoding truncated ΔN 1-131 ΔN 1-131n was introduced as a knock-in transgene into the intestinal gene-specific gpA33 locus of C57Bl/6J mice and combined with various oncogenic driver mutations.
That is, there are likely only several relevant driver mutations and many additional passenger mutations.
Several studies have demonstrated the utility of exome sequencing in identifying novel driver mutations in various cancer types [ 7- 10].
Activating mutations in protein kinases are increasingly recognised as driver mutations in various forms of cancer [7].
To this end, we tested exoDNA isolated from various cancer cell lines for driver mutations known to be present in those cell lines.
Most studies take a gene-based approach to identifying driver mutations, highlighting genes mutated in a large percentage of tumor samples as those likely to contain driver mutations.
These events are called somatic mutations and have been shown to provoke various oncogenic processes 2 (they are called "driver" mutations).
Model 1 (fixed mutation rate) was used for the simulations of genetic diversity, with the mutation rate μ = 10−5 or μ = 10−7 and various values of the selective advantage of driver mutations s d.
Indeed, driver mutations always accrued more quickly than mutator mutations, and the difference in rate was increased as the selective benefit of additional driver mutations increased (Fig. 5D).
Recent developments in cancer genome sequencing technology expanded our knowledge of driver mutations, which were identified as novel candidates for targeted therapy in various cancers.
