Friday, September 22, 2006

Transmissible tumours:
The September 7th edition of Nature Magazine has an article under the News and Views section entitled 'Infectious Tumour Cells' (Vol 443, pp35-36). This article discusses the two types of cancer that are directly transferable from individual to individual under normal conditions. These are the canine transmissible venereal tumour (CTVT) and the devil facial tumour disease (DFTD) of Tasmanian Devils. I have read articles on the latter, but, like most veterinarians, I have been familiar with CTVT for much longer. So my memory lapse can perhaps be forgiven when I quoted to a client recently that CTVT was the only cancer known to be directly infectious "as a cancer". My stock of Tasmanian devil faces in memory is exactly zero, so the second fact easily slips my mind.
In any case the article presents the evidence that these tumours are in fact infectious clones of original tumour cells that arose in animals other than those infected rather than being malignant transformations of the cells of the present host animal. The evidence is much stronger in the case of CTVT. Murgis et al (Cell 126 ,477-487-2006) show that the tumours from dogs across 5 continents are closely related genetically and distinct from the genome of the host dog. They use a combination of techniques [dog leukocyte antigens (dla similar to the human hla), haplotyping (chromosome analysis), microsatellite DNA and mitochondrial DNA sequencing]. The various tumours, "had less genetic variability than that observed within even the most inbred breed of dog".
The evidence for the facial tumours of Tasmanian Devils is less robust. It consists merely of consistent patterns of chromosome abnormalities.
The authors of this review (David Dingli and Martin A. Novak) go on to discuss the limited ways in which tumours are transmitted directly in humans. These include mother to fetus transfer, interfetal transfer in multiple pregnancies and transmission via organ donation. Mercifully such events are quite rare. In the case of organ transplants the rate is 0.04% of solid organ transplants and 0.06% of haematopoietic stem cell transfers.
The reason why cancer generally is not transferable is graft rejection due to the MHC antigens that distinguish self from non-self. CTVT cells reduce their expression of MHCs (the DLA previously mentioned) and thereby avoid graft rejection on the part of killer T cells. They do not, however, totally inhibit the expression of such antigens as this would stimulate attack by the NK (natural killer cells), a less specific form of the cellular immune defenses.
The authors go on to say that this phenomenon is evidence of the theory that the MHC evolved mainly as a defense against tumours.

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