Somatic evolution and global expansion of an ancient transmissible cancer lineage

Adrian Baez-Ortega, Kevin Gori, Andrea Strakova, Janice L. Allen, Karen M. Allum, Leontine Bansse-Issa, Thinlay N. Bhutia, Jocelyn L. Bisson, Cristóbal Briceño, Artemio Castillo Domracheva, Anne M. Corrigan, Hugh R. Cran, Jane T. Crawford, Eric Davis, Karina F. De Castro, Andrigo B. De Nardi, Anna P. De Vos, Laura Delgadillo Keenan, Edward M. Donelan, Adela R. Espinoza HuertaIbikunle A. Faramade, Mohammed Fazil, Eleni Fotopoulou, Skye N. Fruean, Fanny Gallardo-Arrieta, Olga Glebova, Pagona G. Gouletsou, Rodrigo F. Häfelin Manrique, Joaquim J.G.P. Henriques, Rodrigo S. Horta, Natalia Ignatenko, Yaghouba Kane, Cathy King, Debbie Koenig, Ada Krupa, Steven J. Kruzeniski, Young Mi Kwon, Marta Lanza-Perea, Mihran Lazyan, Adriana M. Lopez Quintana, Thibault Losfelt, Gabriele Marino, Simón Martínez Castañeda, Mayra F. Martínez-López, Michael Meyer, Edward J. Migneco, Berna Nakanwagi, Karter B. Neal, Winifred Neunzig, Máire Ní Leathlobhair, Sally J. Nixon, Antonio Ortega-Pacheco, Francisco Pedraza-Ordoñez, Maria C. Peleteiro, Katherine Polak, Ruth J. Pye, John F. Reece, Jose Rojas Gutierrez, Haleema Sadia, Sheila K. Schmeling, Olga Shamanova, Alan G. Sherlock, Maximilian Stammnitz, Audrey E. Steenland-Smit, Alla Svitich, Lester J. Tapia Martínez, Ismail Thoya Ngoka, Cristian G. Torres, Elizabeth M. Tudor, Mirjam G. Van Der Wel, Bogdan A. Viţălaru, Sevil A. Vural, Oliver Walkinton, Jinhong Wang, Alvaro S. Wehrle-Martinez, Sophie A.E. Widdowson, Michael R. Stratton, Ludmil B. Alexandrov, Iñigo Martincorena, Elizabeth P. Murchison

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Abstract

The canine transmissible venereal tumor (CTVT) is a cancer lineage that arose several millennia ago and survives by “metastasizing” between hosts through cell transfer. The somatic mutations in this cancer record its phylogeography and evolutionary history. We constructed a time-resolved phylogeny from 546 CTVT exomes and describe the lineage's worldwide expansion. Examining variation in mutational exposure, we identify a highly context-specific mutational process that operated early in the cancer's evolution but subsequently vanished, correlate ultraviolet-light mutagenesis with tumor latitude, and describe tumors with heritable hyperactivity of an endogenous mutational process. CTVT displays little evidence of ongoing positive selection, and negative selection is detectable only in essential genes. We illustrate how long-lived clonal organisms capture changing mutagenic environments, and reveal that neutral genetic drift is the dominant feature of long-term cancer evolution.

Original languageEnglish (US)
Article number464
JournalScience
Volume365
Issue number6452
DOIs
Publication statusPublished - Aug 2 2019
Externally publishedYes

ASJC Scopus subject areas

  • General

Cite this

Baez-Ortega, A., Gori, K., Strakova, A., Allen, J. L., Allum, K. M., Bansse-Issa, L., ... Murchison, E. P. (2019). Somatic evolution and global expansion of an ancient transmissible cancer lineage. Science, 365(6452), [464]. https://doi.org/10.1126/science.aau9923