Transmissible [corrected] dog cancer genome reveals the origin and history of an ancient cell lineage.

Autor: Murchison EP; Wellcome Trust Sanger Institute, Hinxton, CB10 1SA, UK.; Department of Veterinary Medicine, University of Cambridge, Madingley Road, Cambridge CB3 0ES, UK., Wedge DC; Wellcome Trust Sanger Institute, Hinxton, CB10 1SA, UK., Alexandrov LB; Wellcome Trust Sanger Institute, Hinxton, CB10 1SA, UK., Fu B; Wellcome Trust Sanger Institute, Hinxton, CB10 1SA, UK., Martincorena I; Wellcome Trust Sanger Institute, Hinxton, CB10 1SA, UK., Ning Z; Wellcome Trust Sanger Institute, Hinxton, CB10 1SA, UK., Tubio JMC; Wellcome Trust Sanger Institute, Hinxton, CB10 1SA, UK., Werner EI; Wellcome Trust Sanger Institute, Hinxton, CB10 1SA, UK., Allen J; Animal Management in Rural and Remote Indigenous Communities (AMRRIC), P.O. Box 1464, Nightcliff, NT 0814, Australia., De Nardi AB; 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., Donelan EM; Animal Management in Rural and Remote Indigenous Communities (AMRRIC), P.O. Box 1464, Nightcliff, NT 0814, Australia., Marino G; Department of Veterinary Sciences, University of Messina, 98168 Messina, Italy., Fassati A; 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., Campbell PJ; Wellcome Trust Sanger Institute, Hinxton, CB10 1SA, UK., Yang F; Wellcome Trust Sanger Institute, Hinxton, CB10 1SA, UK., Burt A; Department of Life Sciences, Imperial College London, Silwood Park, Ascot, Berks., SL5 7PY, UK., Weiss RA; 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., Stratton MR; Wellcome Trust Sanger Institute, Hinxton, CB10 1SA, UK.
Jazyk: angličtina
Zdroj: Science (New York, N.Y.) [Science] 2014 Jan 24; Vol. 343 (6169), pp. 437-440.
DOI: 10.1126/science.1247167
Abstrakt: 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.
Databáze: MEDLINE