TY - JOUR
T1 - Migrations of cancer cells through the lens of phylogenetic biogeography
AU - Chroni, Antonia
AU - Miura, Sayaka
AU - Oladeinde, Olumide
AU - Aly, Vivian
AU - Kumar, Sudhir
N1 - Publisher Copyright:
© 2021, The Author(s).
PY - 2021/12
Y1 - 2021/12
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=85113365622&partnerID=8YFLogxK
U2 - 10.1038/s41598-021-96215-9
DO - 10.1038/s41598-021-96215-9
M3 - Article
C2 - 34433859
AN - SCOPUS:85113365622
SN - 2045-2322
VL - 11
JO - Scientific Reports
JF - Scientific Reports
IS - 1
M1 - 17184
ER -