Horizontal transfer of nuclear DNA in transmissible cancer

• 成果类型: Article
• 署名作者: Gori, Kevin; Baez-Ortega, Adrian; Strakova, Andrea; Stammnitz, Maximilian R.; Wang, Jinhong; Chan, Jonathan; Hughes, Katherine; Belkhir, Sophia; Hammel, Maurine; Moralli, Daniela; Bancroft, James; Drydale, Edward; Allum, Karen M.; Brignone, Maria Veronica; Corrigan, Anne M.; de Castro, Karina F.; Donelan, Edward M.; Faramade, Ibikunle A.; Hayes, Alison; Ignatenko, Nataliia; Karmacharya, Rockson; Koenig, Debbie; Lanza-Perea, Marta; Quintana, Adriana M. Lopez; Meyer, Michael; Neunzig, Winifred; Pedraza-Ordonez, Francisco; Phuentshok, Yoenten; Phuntsho, Karma; Ramirez-Ante, Juan C.; Reece, John F.; Schmeling, Sheila K.; Singh, Sanjay; Martinez, Lester J. Tapia; Taulescu, Marian; Thapa, Samir; Thapa, Sunil; van der Wel, Mirjam G.; Wehrle-Martineza, Alvaro S.; Stratton, Michael R.; Murchison, Elizabeth P.
• 署名单位: University of Cambridge; Wellcome Trust Sanger Institute; University of Cambridge; University of Oxford; University of Oxford; University of Buenos Aires; Universidade Estadual Paulista; Universidad de Caldas; University of Agricultural Sciences & Veterinary Medicine Cluj Napoca; Universidad Nacional de Asuncion
• 刊物名称: PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
• ISSN/ISSBN: 0027-13138
• DOI: 10.1073/pnas.2424634122
• 发表日期: 2025-04-22
• 关键词: tumor-cells; EVOLUTION; origins; variants; fusion; clock

摘要

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.