Clone Phylogenetics Reveals Metastatic Tumor Migrations, Maps, and Models

Antonia Chroni; Sayaka Miura; Lauren Hamilton; Tracy Vu; Stephen G Gaffney; Vivian Aly; Sajjad Karim; Maxwell Sanderford; Jeffrey P Townsend; Sudhir Kumar

doi:10.3390/cancers14174326

Clone Phylogenetics Reveals Metastatic Tumor Migrations, Maps, and Models

Cancers (Basel). 2022 Sep 4;14(17):4326. doi: 10.3390/cancers14174326.

Authors

Antonia Chroni^{1

2}, Sayaka Miura^{1

2}, Lauren Hamilton^{1

2}, Tracy Vu^{1

2}, Stephen G Gaffney³, Vivian Aly^{1

2}, Sajjad Karim⁴, Maxwell Sanderford^{1

2}, Jeffrey P Townsend^{3

5

6}, Sudhir Kumar^{1

2

4}

Affiliations

¹ Institute for Genomics and Evolutionary Medicine, Temple University, Philadelphia, PA 19122, USA.
² Department of Biology, Temple University, Philadelphia, PA 19122, USA.
³ Department of Biostatistics, Yale University, New Haven, CT 06510, USA.
⁴ Center for Excellence in Genomic Medicine Research, King Abdulaziz University, Jeddah 22252, Saudi Arabia.
⁵ Department of Ecology and Evolutionary Biology, Yale University, New Haven, CT 06525, USA.
⁶ Program in Computational Biology and Bioinformatics, Yale University, New Haven, CT 06511, USA.

Abstract

Dispersal routes of metastatic cells are not medically detected or even visible. A molecular evolutionary analysis of tumor variation provides a way to retrospectively infer metastatic migration histories and answer questions such as whether the majority of metastases are seeded from clones within primary tumors or seeded from clones within pre-existing metastases, as well as whether the evolution of metastases is generally consistent with any proposed models. We seek answers to these fundamental questions through a systematic patient-centric retrospective analysis that maps the dynamic evolutionary history of tumor cell migrations in many cancers. We analyzed tumor genetic heterogeneity in 51 cancer patients and found that most metastatic migration histories were best described by a hybrid of models of metastatic tumor evolution. Synthesizing across metastatic migration histories, we found new tumor seedings arising from clones of pre-existing metastases as often as they arose from clones from primary tumors. There were also many clone exchanges between the source and recipient tumors. Therefore, a molecular phylogenetic analysis of tumor variation provides a retrospective glimpse into general patterns of metastatic migration histories in cancer patients.

Keywords: cancer; metastasis; molecular evolution; phylodynamics; phylogenetics; tumor evolution.

Abstract

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