Nearing saturation of cancer driver gene discovery

Extensive sequencing efforts of cancer genomes such as The Cancer Genome Atlas (TCGA) have been undertaken to uncover bona fide cancer driver genes which has enhanced our understanding of cancer and revealed therapeutic targets. However, the number of driver gene mutations is bounded, indicating that there must be a point when further sequencing efforts will be excessive. We found that there was a significant positive correlation between sample size and identified driver gene mutations across 33 cancers sequenced by the TCGA, which is expected if additional sequencing is still leading to the identification of more driver genes. However, the rate of new cancer driver genes being discovered with larger samples is declining rapidly. Our analysis provides a general guide for determining which cancer types would likely benefit from additional sequencing efforts, particularly those with relatively high rates of cancer driver gene discovery. Our results argue that past strategies of indiscriminately sequencing as many specimens as possible for all cancer types is becoming inefficient. In addition, without significant investments into applying our knowledge of cancer genomes, we risk sequencing more cancer genomes for the sake of sequencing rather than meaningful patient benefit.