Abstract
Malignant cells leave their initial tumor of growth and disperse to other tissues to form metastases. Dispersals also occur in nature when individuals in a population migrate from their area of origin to colonize other habitats. In cancer, phylogenetic biogeography is concerned with the source and trajectory of cell movements. We examine the suitability of primary features of organismal biogeography, including genetic diversification, dispersal, extinction, vicariance, and founder effects, to describe and reconstruct clone migration events among tumors. We used computer-simulated data to compare fits of seven biogeographic models and evaluate models’ performance in clone migration reconstruction. Models considering founder effects and dispersals were often better fit for the clone phylogenetic patterns, especially for polyclonal seeding and reseeding of metastases. However, simpler biogeographic models produced more accurate estimates of cell migration histories. Analyses of empirical datasets of basal-like breast cancer had model fits consistent with the patterns seen in the analysis of computer-simulated datasets. Our analyses reveal the powers and pitfalls of biogeographic models for modeling and inferring clone migration histories using tumor genome variation data. We conclude that the principles of molecular evolution and organismal biogeography are useful in these endeavors but that the available models and methods need to be applied judiciously.
Highlights
We show how real-case scenarios can benefit from biogeographic models by reconstructing clone migration paths of patients with basal-like breast cancer using published clone p hylogenies[13]
Tumors are populations consisting of a diversity of cancer cells with different genetic profiles that may represent different lineages in the clone phylogeny
One can map the collection of genetic variants that likely arose on individual lineage in a phylogeny
Summary
Biogeographic processes (dashed boxes) are exemplified into the presented clone phylogeny of one primary and four metastases: (i) genetic divergence: diversification within an area, (ii) extinction: lineage disappears from an area, (iii) genetic divergence and expansion: diversification within an area, and dispersal to a new area, and (iv) genetic divergence and distant dispersal: dispersal to a new area, and lineages’ divergence. Tumor clones are colored based on the source of tumor site: primary (green), and metastases M1 (blue), M2 (pink), M3 (gray), and M4 (brown). Our results reveal factors to consider when applying biogeographic models for inferring cancer cell migration paths. We show how real-case scenarios can benefit from biogeographic models by reconstructing clone migration paths of patients with basal-like breast cancer using published clone p hylogenies[13]
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