Grant: Project Grant

Cancer is a genetic disease. However, it is usually not inherited but is instead caused by mutations in DNA that accumulate in cells over time. Each cancer is caused by a few "driver" mutations that unlock cancerous properties of cells, such as endless growth or inability to die. Cancers also have thousands of "passenger" mutations that do not contribute to the disease. Thus, finding driver mutations is like finding needles in a haystack. Hundreds of drivers have been found until now, however most efforts have focused on a few percent of the genome that encodes proteins, the building blocks of cells. The remaining "non-coding" genome is much less understood; however, we know that it controls how genes are activated. While we only know little of non-coding genome, researchers are now finding non-coding mutations that contribute to cancer. With new large whole-genome datasets of cancer, we can better find and describe these mutations. In this project, we will combine advanced computational analysis and wet-lab experiments to find non-coding driver mutations in several major types of cancer. First, we use computer algorithms to sift through a hundred million mutations to find novel drivers. Second, we will build a rich profile for each new driver we find, describing the potential ways it contributes to cancer and whether its presence helps identify high-risk patients. Third, we will study the most prominent drivers with molecular experiments in cancer cells and mouse models. This will allow us to understand precisely how the drivers start cancer or make it more aggressive. Once we figure out how these novel drivers contribute to cancer, we may be able to block their activity to develop new cancer therapies in the future.