Tasmanian DevilThere’s been some buzz about the recent paper on the contagious tumor of Tasmanian devils.1 Clearly the thing is a ghastly disease that’s threatening the Devils with extinction — but from a technical viewpoint, the paper last year on a different transmissible tumor was much more interesting.

The other tumor I’m talking about is canine transmissible venereal tumor (CTVT), and the paper is:
Murgia, C., Pritchard, J. K., Kim, S. Y., Fassati, A., and Weiss, R. A. (2006). Clonal origin and evolution of a transmissible cancer. Cell 126, 477-487 .

Most people haven’t heard of CTVT. (I had, but then I’m a veterinarian originally.) It’s just what it sounds like from the name: A sexually-transmitted cancer that spreads between dogs. (And it does seem to be a pure cancer, not a virus that causes cancer.) Until the Tasmanian Devil contagious tumor, that made CTVT essentially unique; no other tumors are known to be transmissible. (Actually, the Tasmanian Devil paper cites a tumor of Syrian hamsters2 that is apparently transmissible — but I’d never heard of that before, and I’m not clear that it still exists or if it has died out in the past 40 years.)

It turns out that the Tasmanian Devil tumor apparently can spread because it is essentially a self graft. Apparently Devils are highly inbred, and show very little polymorphism at the major histocompatibility complex (MHC) region. As I’ve been pointing out (ad nauseum) lately (see here and the links therein) this is really unusual, as in most vertebrates the MHC region is normally by far the most diverse region of the genome. The MHC region is important in graft rejection — duh, that’s what “histocompatibility” means. Essentially, then, it seems that the Devil tumor can “take” on virtually any other Devil, because it’s recognized as “self” MHC. 3 This is interesting, of course, but there’s nothing surprising about it. Endangered species are commonly inbred — inbred animals lack variation at the MHC4 — and matching MHC allows grafts to take. This is all known.

The canine tumor story is very different. This tumor does not match the recipient dogs’ MHC. The same tumor can infect unrelated dogs, with virtually any MHC; Murgia et al looked at tumor-bearing dogs from around the world (“None of the host dogs showed close relatedness to any of the others, consistent with the fact that they came from three locations in Europe, Asia, and Africa and were mongrels”), and they all carried the same tumor. So why is CTVT not rejected as an allograft?

CTVT phhylogeny Most, if not all, tumors in humans show evidence of having been edited by the immune system. That is, the tumors have altered their MHC expression in some way that probably allows them to evade the immune system. That’s one reason that tumors themselves are not rejected. (Presumably, there are many more proto-tumors that arise during our lifetime, that fail to alter their MHC and are destroyed by our immune systems before there are more than a half-dozen abnormal cells. We only see the successful ones.) CTVT has done this, as well, and expresses very low (but detectable) levels of MHC. Also, again like many other tumors, CTVT expresses an immune modulator, TGFβ. 5 Murgia et al suggest that these are enough to make the tumor invisible to the immune system and allow it to engraft.

But I’m not at all convinced. These changes — low MHC expression, high TGFβ — are very common, if not universal, tumor adaptations, yet CVTV is unique — extraordinarily, spectacularly, unique — in its ability to spread and persist within a highly outbred species. CVTV has persisted for hundreds, if not thousands or even tens of thousands of years:

The precise date when CTVT first occurred is difficult to determine. From its indistinguishable histopathology and its ability to grow as an allograft, it is likely that Novinski (1876) studied the same clone, and CTVT could have become established centuries before this date. Our analysis of divergence of microsatellites indicates that the tumor arose between 200 and 2500 years ago. Whether this time period represents the time the tumor first arose or whether it represents a later bottleneck in the tumor’s dispersion as a parasite cannot be resolved. While this estimated date indicates a relatively recent evolutionary origin, CTVT represents the oldest known mammalian somatic cell in continuous propagation, having undergone countless mitoses and host-to-host transfers.

In fact, the tumor may even predate dogs. The figure to the right from Murgia et al shows the relationship between the tumor and dogs and wolves (click for a larger version)– the thing is even closer to wolves than it is to dogs.

Frankly, the thing is damn creepy, and I kind of hope I’m right and there’s much more to its ability to persist than the really very common changes that have been pointed at so far, because I wouldn’t want to think that every tumor was capable of this kind of behaviour. Whatever it is, though, is more novel and scientifically interesting than the Tasmanian Devil tumor. Hopefully the Devil tumor is easier to deal with than the canine one.


  1. Siddle, H. V., Kreiss, A., Eldridge, M. D., Noonan, E., Clarke, C. J., Pyecroft, S., Woods, G. M., and Belov, K. (2007). Transmission of a fatal clonal tumor by biting occurs due to depleted MHC diversity in a threatened carnivorous marsupial. Proc Natl Acad Sci U S A 104:16221-16226 []
  2. Copper, H. L., Mackay, C. M., And Banfield, W. G. (1964). Chromosome Studies Of A Contagious Reticulum Cell Sarcoma Of The Syrian Hamster. J Natl Cancer Inst 33, 691-706.[]
  3. This is apparently the same mechanism as with the Syrian hamster transmissible tumor; hamsters are highly inbred as well. Streilein, J. W., and Duncan, W. R. (1983). On the anomalous nature of the major histocompatibility complex in Syrian hamsters, Hm-1. Transplant Proc 15, 1540-1545.[]
  4. Though not inevitably. The San Nicolas Island foxes I used as an example were inbred, yet had significant MHC diversity.[]
  5. The Devil paper states that CTVT also “up-regulates nonclassical class I expression to avoid the natural killer cell response” — but I don’t know where they get this from. It’s not in the reference they cite, and I can’t find evidence for it anywhere (but that doesn’t mean it’s not correct) []