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Published on: September 15, 2010
Clonal origin and evolution of a transmissible cancer
Claudio Murgia1, Jonathan K Pritchard, Su Yeon Kim
1MRC/UCL Centre for Medical Molecular Virology, Division of Infection and Immunity, University College London, 46 Cleveland Street, London W1T 4JF, UK.
Cell
|August 12, 2006
Summary
Canine transmissible venereal tumor (CTVT) is caused by the tumor cells themselves, not a virus. Genetic analysis shows CTVT originated from a single clone over 2,000 years ago.
Area of Science:
- Oncology
- Genetics
- Veterinary Medicine
Background:
- Canine transmissible venereal tumor (CTVT) is a naturally occurring contagious cancer in dogs.
- The exact nature of the transmissible agent of CTVT has been a long-standing question in cancer research.
Purpose of the Study:
- To determine if CTVT is transmitted by tumor cells.
- To investigate the genetic origin and evolution of CTVT.
Main Methods:
- Analysis of genetic markers including major histocompatibility (MHC) genes, microsatellites, and mitochondrial DNA (mtDNA).
- Comparison of genetic profiles between naturally occurring CTVT samples and matched host blood samples.
- Phylogenetic analysis of tumor samples from multiple continents.
Main Results:
- CTVT tumors were genetically distinct from their host dogs.
- All analyzed CTVT samples originated from a single neoplastic clone, diverging into two subclades.
- Phylogenetic analysis suggests CTVT originated 200-2500 years ago from a wolf or East Asian dog breed.
- CTVT exhibits high aneuploidy but a stable genotype, with downmodulation of MHC expression during tumor growth.
Conclusions:
- CTVT is a clonal cancer transmitted by living tumor cells.
- The study provides insights into cancer genome instability, allograft transplantation, and the evolution of transmissible cancers.
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