Resolving genetic heterogeneity in cancer by Turajlic, Graham, and Swanton et al 2019
Is cancer a special case of evolution?
Subclones * subpopulations of cells within a tumor distinguished by genetic alterations and growth rates
Current models of tumor evolution
Selection
Branching evolution
Linear evolution
Neutral evolution
Punctuated evolution
Inferring evolutionary mode with genomics
Bulk sequencing
Choice of sequencing assay
Allelic copy number correction
Single-cell sequencing
Detecting selection
Using clone frequency to detect selection
Using mutational patterns to detect selection
Stochasticity versus determinism
Chromosome instability in cancer evolution
CIN and clonal fitness
CIN and clinical outcomes
Evolutionary patterns and patient outcomes
Clonal diversity and clinical outcomes
Punctuated versus gradual evolution and clinical outcomes
Origin of treatment-resistant clones
Resistance to targeted therapies
Resistance to immune checkpoint inhibition
Conclusions and perspective