Overview of strategies for cancer-genome sequencing. A cancer-genome sequencing project begins with whole-genome or whole-exome sequencing. Various methods are used to detect somatic mutations in the resulting sequence (see Table 1), yielding a long list of somatic mutations. Several strategies can then be employed to prioritize these mutations for experimental or functional validation. These strategies include: testing for recurrent mutations, predicting functional impact, and assessing combinations of mutations (see Table 2). None of these approaches are perfect, and each returns a subset of driver mutations as well as passenger mutations. The mutations returned by these approaches can then be validated using a variety of experimental techniques.