Abstract | Human cancer is caused by the accumulation of genetic alterations in cells. Many of these mutations are currently being catalogued in the context of large cancer genome projects, but it is not clear how to prioritize the functional validation of the biologically most relevant genetic events within the large number of candidate mutations. Of special importance are those changes that occur early during malignant transformation since they may result in rewiring of the signaling circuitry or confer a state of addiction to the new signal, and thus represent particularly promising targets for therapeutic intervention. I will describe a new computational approach, called Retracing the Evolutionary Steps In Cancer (RESIC), to deduce the temporal sequence of genetic events arising during tumorigenesis from cross-sectional genomic data of tumors at their fully transformed stage. This approach is tested with data from advanced colorectal cancer samples and then applied to primary glioblastoma and lung adenocarcinoma. |