Transmissible [corrected] dog cancer genome reveals the origin and history of an ancient cell lineage.
Canine transmissible venereal tumor (CTVT) is the oldest known somatic cell lineage. It is a transmissible cancer that propagates naturally in dogs. We sequenced the genomes of two CTVT tumors and found that CTVT has acquired 1.9 million somatic substitution mutations and bears evidence of exposure to ultraviolet light. CTVT is remarkably stable and lacks subclonal heterogeneity despite thousands of rearrangements, copy-number changes, and retrotransposon insertions. More than 10,000 genes carry nonsynonymous variants, and 646 genes have been lost. CTVT first arose in a dog with low genomic heterozygosity that may have lived about 11,000 years ago. The cancer spawned by this individual dispersed across continents about 500 years ago. Our results provide a genetic identikit of an ancient dog and demonstrate the robustness of mammalian somatic cells to survive for millennia despite a massive mutation burden.
Wellcome Trust Sanger Institute, Hinxton, CB10 1SA, UK.|Department of Veterinary Medicine, University of Cambridge, Madingley Road, Cambridge CB3 0ES, UK.
Elizabeth P
EP
Murchison
Wellcome Trust Sanger Institute, Hinxton, CB10 1SA, UK.
David C
DC
Wedge
Wellcome Trust Sanger Institute, Hinxton, CB10 1SA, UK.
Ludmil B
LB
Alexandrov
Wellcome Trust Sanger Institute, Hinxton, CB10 1SA, UK.
Beiyuan
B
Fu
Wellcome Trust Sanger Institute, Hinxton, CB10 1SA, UK.
Inigo
I
Martincorena
Wellcome Trust Sanger Institute, Hinxton, CB10 1SA, UK.
Zemin
Z
Ning
Wellcome Trust Sanger Institute, Hinxton, CB10 1SA, UK.
Jose M C
JMC
Tubio
Wellcome Trust Sanger Institute, Hinxton, CB10 1SA, UK.
Emma I
EI
Werner
Animal Management in Rural and Remote Indigenous Communities (AMRRIC), P.O. Box 1464, Nightcliff, NT 0814, Australia.
Jan
J
Allen
Department of Clinical and Veterinary Surgery, São Paulo State University - UNESP, Via de Acesso Prof. Paulo Donato Castellane, s/n. CEP: 14884-900, Jaboticabal, São Paulo, Brazil.
Andrigo Barboza
AB
De Nardi
Animal Management in Rural and Remote Indigenous Communities (AMRRIC), P.O. Box 1464, Nightcliff, NT 0814, Australia.
Edward M
EM
Donelan
Department of Veterinary Sciences, University of Messina, 98168 Messina, Italy.
Gabriele
G
Marino
Wohl Virion Centre and MRC Centre for Medical and Molecular Virology, Division of Infection and Immunity, University College London, Gower Street, London WC1E 6BT, UK.
Ariberto
A
Fassati
Wellcome Trust Sanger Institute, Hinxton, CB10 1SA, UK.
Peter J
PJ
Campbell
Wellcome Trust Sanger Institute, Hinxton, CB10 1SA, UK.
Fengtang
F
Yang
Department of Life Sciences, Imperial College London, Silwood Park, Ascot, Berks., SL5 7PY, UK.
Austin
A
Burt
Wohl Virion Centre and MRC Centre for Medical and Molecular Virology, Division of Infection and Immunity, University College London, Gower Street, London WC1E 6BT, UK.
Robin A
RA
Weiss
Wellcome Trust Sanger Institute, Hinxton, CB10 1SA, UK.
Michael R
MR
Stratton
D000818:Animals; D019070:Cell Lineage / Q000235:genetics*; D004283:Dog Diseases / Q000235:genetics*; D004285:Dogs / Q000235:genetics*; D018703:Founder Effect; D018628:Gene Dosage; D016678:Genome; D059785:Karyotype; D009154:Mutation; D018626:Retroelements; D014685:Venereal Tumors, Veterinary / Q000453:epidemiology* / Q000235:genetics*
D018626:Retroelements