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Pathogenesis and evolution of canine transmissible venereal tumour

Canine Transmissible Venereal Tumour (CTVT) is a neoplastic disease occurring naturally in dogs. CTVT is usually sexually transmitted, but transmission may occur by licking, biting, or scratching tumour-affected areas. Cytogenetic studies directed to verify the cell transmissibility of the CTVT showed that the tumour cells are characterized by a rearranged karyotype, which is similar in tumours from in different parts of the world. Thus it was postulated that that the transmissible agent causing the CTVT is the tumour cell itself and that all worldwide CTVT have a clonal origin. Given the lack of a definitive proof of the cellular transmission and clonal origin of CTVT, in this PhD project, I tested this hypothesis by analysing the genetic distance between host and tumour and between tumours, using molecular genetic markers including major histocompatibility (MHC) genes, microsatellite loci, and mitochondrial (mt) DNA in matched tumour and normal tissues from naturally occurring tumours collected worldwide. Here I demonstrate that tumours are genetically distinct from their hosts and that the tumours obtained from 5 different continents are derived from a single neoplastic clone. During its evolution CTVT has diverged into two distinct phylogenetic subclades. Although naturally occurring CTVTs are observed only in dogs, CTVT has been reported to be experimentally transmitted by inoculation of tumour cells in other species of the Canidae family such as foxes, coyotes and jackals, thus raising questions about its capacity to grow as an allograft or xenograft and its phylogenetic origin of CTVT. I therefore examined MHC gene transcription in a progressive growing tumour and observed MHC class I and II downregulation. In this study phylogenetic analyses indicate that CTVT most likely originated from a wolf or an East Asian breed of dog. CTVT has been described for the first time in 1876 by Novinsky, thus arguing for an age of at least 130 years old. Here phylogenetic analysis based on microsatellites suggests that CTVT originated between 250 and 2500 years ago.
Date January 2004
CreatorsMurgia, Claudio
PublisherUniversity College London (University of London)
Source SetsEthos UK
Detected LanguageEnglish
TypeElectronic Thesis or Dissertation

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