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Review
. 2017 Apr;1867(2):151-161.
doi: 10.1016/j.bbcan.2017.01.003. Epub 2017 Jan 19.

Tumor evolution: Linear, branching, neutral or punctuated?

Alexander Davis  1 , Ruli Gao  2 , Nicholas Navin  3
Affiliations
Review

Tumor evolution: Linear, branching, neutral or punctuated?

Alexander Davis et al. Biochim Biophys Acta Rev Cancer. 2017 Apr.

Abstract

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.

Keywords: Cancer biology; Cancer genomics; Genome evolution; Intratumor heterogeneity; Single cell genomics; Tumor evolution.

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Figures

Fig. 1
Fig. 1
Models of tumor evolution. Illustration of tumor evolution models showing dynamic changes in clonal frequencies over time. This figure is based on the original publication by Marusyk and Polyak [8]. (A) Linear Evolution (B) Branching Evolution (C) Neutral Evolution (D) Punctuated Evolution. Colors indicate clones with different genotypes.
Fig. 2
Fig. 2
Sequencing methods for resolving intratumor heterogeneity. NGS methods for resolving intratumor heterogeneity. (A) Heterogeneous tumor with five clonal subpopulations indicated by different colors (B) Deep-sequencing and clustering of mutation frequencies (C) multi-region sequencing of different spatial regions in the tumor mass (D) single cell DNA sequencing of individual tumor cells isolated from the tumor.
Fig. 3
Fig. 3
Progression of ITH in tumor evolution models. Changes in intratumor heterogeneity during tumor progression in the context of different tumor evolution models. (A) Linear evolution (B) Branching Evolution (C) Punctuated Evolution (D) Neutral Evolution. Colors indicate different genotypes of clones.
Fig. 4
Fig. 4
Clonal lineages and phylogenetic trees. Phylogenetic trees expected from different models of tumor evolution (A) Linear Evolution (B) Branching Evolution (C) Neutral Evolution (D) Punctuated Evolution. Colors indicate clones with different genotypes.
See this image and copyright information in PMC

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