Cancer is a disease of genetic alterations. In particular, single nucleotide variants (SNVs) present as either germline or somatic point mutations are essential drivers of tumorigenesis and cellular proliferation in many human cancer types. The discovery of germline mutations established important gene functions in cancer; however, the contribution of single germline alleles to the population burden of cancer is relatively low. In contrast, determination of tumorigenic mechanisms has focused on somatic mutations. The somatic mutational landscape of cancer has to date largely been derived from small-scale or targeted approaches, leading to the discovery of genes affected by somatic mutations in many diverse cancer types. More comprehensive studies using Sanger-based exon resequencing suggest that the mutational landscape will be characterized by relative handfuls of frequently mutated genes and a long tail of infrequent somatic mutations in many genes (Jones et al., 2008; Stratton et al., 2009).
