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Science. 2019 Aug 2;365(6452). pii: eaau9923. doi: 10.1126/science.aau9923.

Somatic evolution and global expansion of an ancient transmissible cancer lineage.

Author information

1
Transmissible Cancer Group, Department of Veterinary Medicine, University of Cambridge, Cambridge, UK.
2
Animal Management in Rural and Remote Indigenous Communities (AMRRIC), Darwin, Australia.
3
World Vets, Gig Harbor, USA.
4
Animal Shelter, Stichting Dierenbescherming Suriname, Paramaribo, Suriname.
5
Sikkim Anti-Rabies and Animal Health Programme, Department of Animal Husbandry, Livestock, Fisheries and Veterinary Services, Government of Sikkim, India.
6
Royal (Dick) School of Veterinary Studies and the Roslin Institute, University of Edinburgh, Easter Bush Campus, Roslin EH25 9RG, UK.
7
ConserLab, Animal Preventive Medicine Department, Faculty of Animal and Veterinary Sciences, University of Chile, Santiago, Chile.
8
Corozal Veterinary Hospital, University of Panamá, Panama City, Republic of Panama.
9
St. George's University, True Blue, Grenada.
10
The Nakuru District Veterinary Scheme Ltd, Nakuru, Kenya.
11
Animal Medical Centre, Belize City, Belize.
12
International Animal Welfare Training Institute, UC Davis School of Veterinary Medicine, Davis, CA, USA.
13
Centro Universitário de Rio Preto (UNIRP), São José do Rio Preto, São Paulo, Brazil.
14
Department of Clinical and Veterinary Surgery, São Paulo State University (UNESP), São Paulo, Brazil.
15
Ladybrand Animal Clinic, Ladybrand, South Africa.
16
Veterinary Clinic Sr. Dog's, Guadalajara, Mexico.
17
World Vets Latin America Veterinary Training Center, Granada, Nicaragua.
18
National Veterinary Research Institute, Vom, Nigeria.
19
Animal Clinic, Mombasa, Kenya.
20
Intermunicipal Stray Animals Care Centre (DIKEPAZ), Perama, Greece.
21
Animal Protection Society of Samoa, Apia, Samoa.
22
Faculty of Veterinary Science, University of Zulia, Maracaibo, Venezuela.
23
Veterinary Clinic BIOCONTROL, Moscow, Russia.
24
Faculty of Veterinary Medicine, School of Health Sciences, University of Thessaly, Karditsa, Greece.
25
Veterinary Clinic El Roble, Animal Healthcare Network, Faculty of Animal and Veterinary Sciences, University of Chile, Santiago de Chile, Chile.
26
OnevetGroup, Hospital Veterinário Berna, Lisboa, Portugal.
27
Universidade Vila Velha, Vila Velha, Brazil.
28
Veterinary Clinic Zoovetservis, Kiev, Ukraine.
29
École Inter-états des Sciences et Médecine Vétérinaires de Dakar, Dakar, Senegal.
30
Department of Small Animal Medicine, Faculty of Veterinary Medicine, Utrecht University, Utrecht, Netherlands.
31
Vetexpert Veterinary Group, Yerevan, Armenia.
32
Veterinary Clinic Lopez Quintana, Maldonado, Uruguay.
33
Clinique Veterinaire de Grand Fond, Saint Gilles les Bains, Reunion, France.
34
Department of Veterinary Sciences, University of Messina, Messina, Italy.
35
Facultad de Medicina Veterinaria y Zootecnia, Universidad Autónoma del Estado de México, Toluca, Mexico.
36
School of Veterinary Medicine, Universidad de las Américas, Quito, Ecuador.
37
Cancer Development and Innate Immune Evasion Lab, Champalimaud Center for the Unknown, Lisbon, Portugal.
38
Touray & Meyer Vet Clinic, Serrekunda, The Gambia.
39
Hillside Animal Hospital, St. Louis, MO, USA.
40
The Kampala Veterinary Surgery, Kampala, Uganda.
41
Asavet Veterinary Charities, Tucson, AZ, USA.
42
Vets Beyond Borders, Bylakuppe, India.
43
Faculty of Veterinary Medicine, Autonomous University of Yucatan, Merida, Mexico.
44
Laboratorio de Patología Veterinaria, Universidad de Caldas, Manizales, Colombia.
45
Interdisciplinary Centre of Research in Animal Health (CIISA), Faculty of Veterinary Medicine, University of Lisbon, Lisboa, Portugal.
46
Four Paws International, Vienna, Austria.
47
Vets Beyond Borders, The Rocks, Australia.
48
Help in Suffering, Jaipur, India.
49
Veterinary Clinic Dr José Rojas, Los Andes, Chile.
50
Department of Biotechnology, Balochistan University of Information Technology, Engineering and Management Sciences, Quetta, Pakistan.
51
Corozal Veterinary Clinic, Corozal Town, Belize.
52
Veterinary Clinic Vetmaster, Ramenskoye, Russia.
53
State Hospital of Veterinary Medicine, Dniprodzerzhynsk, Ukraine.
54
Jomo Kenyatta University of Agriculture and Technology, Juja, Kenya.
55
Laboratory of Biomedicine and Regenerative Medicine, Department of Clinical Sciences, Faculty of Animal and Veterinary Sciences, University of Chile, Santiago, Chile.
56
Faculty of Veterinary and Agricultural Sciences, University of Melbourne, Melbourne, Australia.
57
Animal Anti Cruelty League, Port Elizabeth, South Africa.
58
Clinical Sciences Department, Faculty of Veterinary Medicine Bucharest, Bucharest, Romania.
59
Department of Pathology, Faculty of Veterinary Medicine, Ankara University, Ankara, Turkey.
60
Faculty of Veterinary Sciences, National University of Asuncion, San Lorenzo, Paraguay.
61
Lilongwe Society for Protection and Care of Animals (LSPCA), Lilongwe, Malawi.
62
Wellcome Sanger Institute, Hinxton, UK.
63
Department of Cellular and Molecular Medicine, University of California, San Diego, La Jolla, CA, USA.
64
Transmissible Cancer Group, Department of Veterinary Medicine, University of Cambridge, Cambridge, UK. epm27@cam.ac.uk.
#
Contributed equally

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.

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PMID:
31371581
DOI:
10.1126/science.aau9923

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