Horizontal transfer of nuclear DNA in transmissible cancer
Horizontal transfer of nuclear DNA between cells of host and cancer is a potential source of adaptive variation in cancer cells. An understanding of the frequency and significance of this process in naturally occurring tumors is, however, lacking. We screened for this phenomenon in the transmissible cancers of dogs and Tasmanian devils and found an instance in the canine transmissible venereal tumor (CTVT). This involved introduction of a 15-megabase dicentric genetic element, composed of 11 fragments of six chromosomes, to a CTVT sublineage occurring in Asia around 2,000 y ago. The element forms the short arm of a small submetacentric chromosome and derives from a dog with ancestry associated with the ancient Middle East. The introduced DNA fragment is transcriptionally active and has adopted the expression profile of CTVT. Its features suggest that it may derive from an engulfed apoptotic body. Our findings indicate that nuclear horizontal gene transfer, although likely a rare event in tumor evolution, provides a viable mechanism for the acquisition of genetic material in naturally occurring cancer genomes.
Authors
- Katherine Hughes (ORCID: https://orcid.org/0000-0002-3331-1249)
- Juan C. Ramirez-Ante (ORCID: https://orcid.org/0000-0003-3747-7462)
- Sheila K. Schmeling (ORCID: https://orcid.org/0000-0003-3828-9818)
- Francisco Pedraza (ORCID: https://orcid.org/0000-0002-3217-8941)
- Kevin Gori (ORCID: https://orcid.org/0000-0001-7975-4275)
- Daniela Moralli (ORCID: https://orcid.org/0000-0001-7977-8496)
- Andrea Strakova (ORCID: https://orcid.org/0000-0001-6221-5515)
- Marta Lanza‐Perea
- Edward M. Donelan (ORCID: https://orcid.org/0000-0001-8035-3057)
- Edward Drydale (ORCID: https://orcid.org/0000-0003-4357-2546)
- Alvaro Wehrle-Martinez (ORCID: https://orcid.org/0000-0002-3515-9164)
- Lester J. Tapia Martínez
- James Bancroft (ORCID: https://orcid.org/0000-0002-6644-3432)
- Maximilian R. Stammnitz (ORCID: https://orcid.org/0000-0002-1704-9199)
- Debbie Koenig
- Mirjam G. van der Wel
- Ibikunle A. Faramade (ORCID: https://orcid.org/0000-0003-4375-6011)
- Adriana M. Lopez Quintana (ORCID: https://orcid.org/0000-0003-0989-3397)
- Marian Taulescu (ORCID: https://orcid.org/0000-0002-8987-6038)
- Michael R. Stratton (ORCID: https://orcid.org/0000-0001-6035-153X)
- Sunil Thapa (ORCID: https://orcid.org/0009-0003-6658-6075)
- Karma Phuntsho
- Anne M. Corrigan
- Winifred Neunzig
- Nataliia Ignatenko (ORCID: https://orcid.org/0000-0001-9310-2863)
- Adrian Baez‐Ortega (ORCID: https://orcid.org/0000-0002-9201-4420)
- Karen M. Allum
- M. Hammel (ORCID: https://orcid.org/0000-0001-9937-5678)
- Elizabeth P. Murchison (ORCID: https://orcid.org/0000-0001-7462-8907)
- Michael J. Meyer (ORCID: https://orcid.org/0000-0003-1587-5347)
- Jinhong Wang
- Jonathan C.H. Chan (ORCID: https://orcid.org/0000-0003-4232-4372)
- Karina Ferreira de Castro
- Alison Hayes
- Rockson Karmacharya
- Yoenten Phuentshok
- Sophia Belkhir
- John F. Reece
- M. Brignone
- Samir Thapa
- Sanjay Singh (ORCID: https://orcid.org/0000-0001-8943-4208)
Institutions
- St. George's University (GD)
- University of Agricultural Sciences, Dharwad (IN)
- University of Caldas (CO)
- University of Cambridge (GB)
- Universidad de Buenos Aires (AR)
- Wellcome Sanger Institute (GB)
- University of Oxford (GB)
- Centre For Human Genetics (IN)
- Meyer (China) (CN)
- Veterinary Medical Center (JP)
- DNA Diagnostic (Denmark) (DK)
- Nepal Agricultural Research Council (NP)
- Corporación Universitaria Santa Rosa de Cabal (CO)
- Centre for Rural and Remote Mental Health (AU)
- Universidad Nacional de Asunción (PY)
- Universidade Estadual Paulista (Unesp) (BR)
Publication Details
- Journal
- Proceedings of the National Academy of Sciences
- Published
- 2025-04-22
- DOI
- https://doi.org/10.1073/pnas.2424634122
- Citations
- 1
- Primary Topic
- Veterinary Oncology Research
- Type
- article
- Field-Weighted Citation Impact
- 1.52
Funders
- Wellcome Trust
- Biotechnology and Biological Sciences Research Council