Tumor evolution: Linear, branching, neutral or punctuated?

Alexander Davis, Ruli Gao, Nicholas Navin

Research output: Contribution to journalArticlepeer-review

214 Scopus citations


Intratumor heterogeneity has been widely reported in human cancers, but our knowledge of how this genetic diversity emerges over time remains limited. A central challenge in studying tumor evolution is the difficulty in collecting longitudinal samples from cancer patients. Consequently, most studies have inferred tumor evolution from single time-point samples, providing very indirect information. These data have led to several competing models of tumor evolution: linear, branching, neutral and punctuated. Each model makes different assumptions regarding the timing of mutations and selection of clones, and therefore has different implications for the diagnosis and therapeutic treatment of cancer patients. Furthermore, emerging evidence suggests that models may change during tumor progression or operate concurrently for different classes of mutations. Finally, we discuss data that supports the theory that most human tumors evolve from a single cell in the normal tissue. This article is part of a Special Issue entitled: Evolutionary principles - heterogeneity in cancer?, edited by Dr. Robert A. Gatenby.

Original languageEnglish (US)
Pages (from-to)151-161
Number of pages11
JournalBiochimica et Biophysica Acta - Reviews on Cancer
Issue number2
StatePublished - Apr 2017


  • Cancer biology
  • Cancer genomics
  • Genome evolution
  • Intratumor heterogeneity
  • Single cell genomics
  • Tumor evolution

ASJC Scopus subject areas

  • Oncology
  • Genetics
  • Cancer Research


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