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BIBTEX RIS

Somatic evolution and global expansion of an ancient transmissible cancer lineage

2019; American Association for the Advancement of Science; Volume: 365; Issue: 6452 Linguagem: Inglês

10.1126/science.aau9923

1095-9203

Adrian Baez‐Ortega, Kevin Gori, Andrea Strakova, Janice L. Allen, Karen M. Allum, Leontine Bansse-Issa, Thinlay N. Bhutia, Jocelyn Bisson, Cristóbal Briceño, Artemio Castillo Domracheva, Anne M. Corrigan, Hugh R. Cran, Jane T. Crawford, Eric Davis, Karina Ferreira de Castro, Andrígo Barboza De Nardi, Anna P. de Vos, Laura Keenan, Edward M. Donelan, Adela R. Espinoza Huerta, Ibikunle A. Faramade, Mohammed Fazil, Eleni Fotopoulou, Skye N. Fruean, Fanny Gallardo-Arrieta, Olga Glebova, Pagona G. Gοuletsοu, Rodrigo F. Häfelin Manrique, Joaquim Henriques, Rodrigo dos Santos Horta, Natalia A. Ignatenko, Yaghouba Kane, Cathy King, Debbie Koenig, A. Krupa, Steven J. Kruzeniski, Young-Mi Kwon, Marta Lanza‐Perea, Mihran Lazyan, Adriana M. Lopez Quintana, Thibault Losfelt, Gabriele Marino, José Simón Martínez-Castañeda, Mayra Fernanda Martínez-López, Michael J. Meyer, Edward J. Migneco, Berna Nakanwagi, Karter B. Neal, Winifred Neunzig, Máire Ní Leathlobhair, Sally J. Nixon, Antonio Ortega‐Pacheco, Francisco Pedraza, 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 R. 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 Alexandru Vițălaru, Sevil Atalay Vural, Oliver Walkinton, Jinhong Wang, Alvaro Wehrle-Martinez, Sophie A. E. Widdowson, Michael R. Stratton, Ludmil B. Alexandrov, Iñigo Martincorena, Elizabeth P. Murchison,

CRISPR and Genetic Engineering

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.