1. Somatic evolution and global expansion of an ancient transmissible cancer lineage.
- Author
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Baez-Ortega A, Gori K, Strakova A, Allen JL, Allum KM, Bansse-Issa L, Bhutia TN, Bisson JL, Briceño C, Castillo Domracheva A, Corrigan AM, Cran HR, Crawford JT, Davis E, de Castro KF, B de Nardi A, de Vos AP, Delgadillo Keenan L, Donelan EM, Espinoza Huerta AR, Faramade IA, Fazil M, Fotopoulou E, Fruean SN, Gallardo-Arrieta F, Glebova O, Gouletsou PG, Häfelin Manrique RF, Henriques JJGP, Horta RS, Ignatenko N, Kane Y, King C, Koenig D, Krupa A, Kruzeniski SJ, Kwon YM, Lanza-Perea M, Lazyan M, Lopez Quintana AM, Losfelt T, Marino G, Martínez Castañeda S, Martínez-López MF, Meyer M, Migneco EJ, Nakanwagi B, Neal KB, Neunzig W, Ní Leathlobhair M, Nixon SJ, Ortega-Pacheco A, Pedraza-Ordoñez F, Peleteiro MC, Polak K, Pye RJ, Reece JF, Rojas Gutierrez J, Sadia H, Schmeling SK, Shamanova O, Sherlock AG, Stammnitz M, Steenland-Smit AE, Svitich A, Tapia Martínez LJ, Thoya Ngoka I, Torres CG, Tudor EM, van der Wel MG, Viţălaru BA, Vural SA, Walkinton O, Wang J, Wehrle-Martinez AS, Widdowson SAE, Stratton MR, Alexandrov LB, Martincorena I, and Murchison EP
- Subjects
- Animals, Dog Diseases epidemiology, Dogs, Exosomes, Gene Expression, Mutagenesis, Phylogeny, Selection, Genetic, Venereal Tumors, Veterinary epidemiology, Clonal Evolution genetics, Dog Diseases classification, Dog Diseases genetics, Venereal Tumors, Veterinary classification, Venereal Tumors, Veterinary genetics
- 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., (Copyright © 2019 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works.)
- Published
- 2019
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