Neutral tumor evolution: a theoretical perspective

Recent work of Sottoriva, Graham, and collaborators have led to the controversial claim that exponentially growing tumors have a site frequency spectrum that follows the $1/f$ law consistent with neutral evolution. This conclusion has been criticized based on data quality issues, statistical considerations, and simulation results. Here, we use rigorous mathematical arguments to investigate the site frequency spectrum in the two-type model of clonal evolution. If the fitnesses of the two types are $\lambda_0<\lambda_1$, then the site frequency spectrum is $c/f^\alpha$ where $\alpha=\lambda_0/\lambda_1$. This is due to the advantageous mutations that produce the founders of the type 1 population. Mutations within the growing type 0 and type 1 populations follow the $1/f$ law. Our results show that, in contrast to published criticisms, neutral evolution in an exponentially growing tumor can be distinguished from the two-type model using the site frequency spectrum. Email ciocanel@math.duke.edu to request the Zoom link and password for the talk (or subscribe to announcements at https://lists.duke.edu/sympa/info/mathbio-seminar).