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Clonal replacement and heterogeneity in breast tumors treated with neoadjuvant HER2-targeted therapy

Genomic changes observed across treatment may result from either clonal evolution or geographically disparate sampling of heterogeneous tumors. Here we use computational modeling based on analysis of fifteen primary breast tumors and find that …

Genetic Load and Potential Mutational Meltdown in Cancer Cell Populations

Large genomes with elevated mutation rates are prone to accumulating deleterious mutations more rapidly than natural selection can purge (Muller’s ratchet). As a consequence, it may lead to the extinction of small populations. Relative to most …

Is the evolution in tumors Darwinian or non-Darwinian?

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Big Bang tumor growth and clonal evolution

The advent and application of next-generation sequencing (NGS) technologies to tumor genomes has reinvigorated efforts to understand clonal evolution. Although tumor progression has traditionally been viewed as a gradual stepwise process, recent …

Between-region genetic divergence reflects the mode and tempo of tumor evolution

Spatial computational modeling of tumor growth identifies the evolutionary mode of tumor clonal expansions.

A population genetics perspective on the determinants of intra-tumor heterogeneity

In this review, we provide a population genetics perspective on the determinants of intra-tumor heterogeneity and approaches to quantify genetic diversity. We summarize evidence for different modes of evolution based on recent cancer genome sequencing studies and discuss emerging evolutionary strategies to therapeutically exploit tumor heterogeneity.

Inferring tumor phylogenies from multi-region sequencing

A new computational method illuminates the heterogeneity and evolutionary histories of cells within a tumor.

Extremely high genetic diversity in a single tumor points to prevalence of non-Darwinian cell evolution

The extreme genetic diversity in a single liver tumor implies clonal evolution under the non-Darwinian mode.

Age-dependent transition from cell-level to population-level control in murine intestinal homeostasis revealed by coalescence analysis

Using population genetic theory together with single-cell sequencing data collected from mouse intestinal crypts at two points in development, we have revealed a dynamic picture of stem cell renewal in intestinal crypts.