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Delineating the longitudinal tumor evolution using organoid models

Looking backward in time to define the chronology of metastasis

The timing of cancer metastasis has implications for treatment and prevention. Traditional forward-time views of metastasis assume it occurs late during evolution. However, looking backward in time reveals metastasis often occurs prior to clinical …

Multi-cancer analysis of clonality and the timing of systemic spread in paired primary tumors and metastases

Analysis of WES data from 457 paired primary tumor and metastatic samples in three cancer types reveals early metastatic seeding and the impact of drug treatment on metastatic clonal evolution.

Quantitative evidence for early metastatic seeding in colorectal cancer

Analysis of genomic data within a spatial tumor growth model and statistical inference framework indicates that early disseminated cells commonly seed metastases while the carcinoma is clinically undetectable.

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.