Signatures of neutral evolution in exponentially growing tumors: A theoretical perspective.

Journal Article (Journal Article)

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 λ0 < λ1, then the site frequency spectrum is c/fα where α = λ0/λ1. 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.

Full Text

Duke Authors

Cited Authors

  • Tung, H-R; Durrett, R

Published Date

  • February 11, 2021

Published In

Volume / Issue

  • 17 / 2

Start / End Page

  • e1008701 -

PubMed ID

  • 33571199

Pubmed Central ID

  • PMC7904140

Electronic International Standard Serial Number (EISSN)

  • 1553-7358

International Standard Serial Number (ISSN)

  • 1553-734X

Digital Object Identifier (DOI)

  • 10.1371/journal.pcbi.1008701

Language

  • eng