Quantifying Clonal and Subclonal Passenger Mutations in Cancer Evolution

• DOI: 10.1371/journal.pcbi.1004731
• Publication Date: 2016-02-01T19:39:04Z
• Authors: Ivana Bozic; Jeffrey M. Gerold; Martin A. Nowak
• Keywords: Molecular clock; Neutral mutation

The vast majority of mutations in the exome cancer cells are passengers, which do not affect reproductive rate cell. Passengers can provide important information about evolutionary history an individual cancer, and serve as a molecular clock. also become targets for immunotherapy or confer resistance to treatment. We study stochastic expansion population describing growth primary tumors metastatic lesions. first analyze process by looking forward time calculate fixation probabilities frequencies successive passenger ordered their appearance. compute likelihood specific trees, thereby informing phylogenetic reconstruction evolution patients. Next, we derive results backward time: given subclonal mutation estimate number that were present at when arose. exact formulas expected numbers any frequency. Fitting this formula sequencing data leads ratio birth death rates during early stages clonal expansion.