Somatic evolution and global expansion of an ancient transmissible cancer lineage.
Baez-Ortega, Adrian 1; Gori, Kevin 1,*; Strakova, Andrea ,1,*; Allen, Janice L. 2; Allum, Karen M. 3; Bansse-Issa, Leontine 4; Bhutia, Thinlay N. 5; Bisson, Jocelyn L. 1,6; Briceno, Cristobal 7; Castillo Domracheva, Artemio 8; Corrigan, Anne M. 9; Cran, Hugh R. 10; Crawford, Jane T. 11; Davis, Eric 12; de Castro, Karina F. 13; B. de Nardi, Andrigo 14; de Vos, Anna P. 15; Delgadillo Keenan, Laura 16; Donelan, Edward M. 2; Espinoza Huerta, Adela R. 17; Faramade, Ibikunle A. 18; Fazil, Mohammed 19; Fotopoulou, Eleni 20; Fruean, Skye N. 21; Gallardo-Arrieta, Fanny 22; Glebova, Olga 23; Gouletsou, Pagona G. 24; Hafelin Manrique, Rodrigo F. 25; Henriques, Joaquim J. G. P. 26; Horta, Rodrigo S. 27; Ignatenko, Natalia 28; Kane, Yaghouba 29; King, Cathy 3; Koenig, Debbie 3; Krupa, Ada 30; Kruzeniski, Steven J. 17; Kwon, Young-Mi 1; Lanza-Perea, Marta 9; Lazyan, Mihran 31; Lopez Quintana, Adriana M. 32; Losfelt, Thibault 33; Marino, Gabriele 34; Martinez Castaneda, Simon 35; Martinez-Lopez, Mayra F. 36,37; Meyer, Michael 38; Migneco, Edward J. 39; Nakanwagi, Berna 40; Neal, Karter B. 41; Neunzig, Winifred 3; Ni Leathlobhair, Maire 1; Nixon, Sally J. 42; Ortega-Pacheco, Antonio 43; Pedraza-Ordonez, Francisco 44; Peleteiro, Maria C. 45; Polak, Katherine 46; Pye, Ruth J. 47; Reece, John F. 48; Rojas Gutierrez, Jose 49; Sadia, Haleema 50; Schmeling, Sheila K. 51; Shamanova, Olga 52; Sherlock, Alan G. 47; Stammnitz, Maximilian 1; Steenland-Smit, Audrey E. 4; Svitich, Alla 53; Tapia Martinez, Lester J. 17; Thoya Ngoka, Ismail 54; Torres, Cristian G. 55; Tudor, Elizabeth M. 56; van der Wel, Mirjam G. 57; Vitalaru, Bogdan A. 58; Vural, Sevil A. 59; Walkinton, Oliver 47; Wang, Jinhong 1; Wehrle-Martinez, Alvaro S. 60; Widdowson, Sophie A. E. 61; Stratton, Michael R. 62; Alexandrov, Ludmil B. 63; Martincorena, Inigo 62; Murchison, Elizabeth P. ,,1,+
[Article]
Science.
365(6452), August 02, 2019.
(Format: HTML, PDF)
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.
Copyright (C) 2019 by the American Association for the Advancement of Science