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Chapter 3 - The allograft theory

3.7 Different strains of DFTD

Pearse and Swift had continued to observe the DFTD tumour cells at the DPIPWE Mt Pleasant laboratory and continued to observe increasing instability in the chromosomes of the DFTD tumour cells.119 They also observed that devil tumour cells from particular locations on the island shared the same chromosomal abnormalities. These sets of chromosomes (strains 2–4) were different from the original DFTD chromosomes (strain 1) published in the Nature article as shown in the illustrations Figures 3:3 and 3:4 below.

118 Obendorf DL & McGlashan ND, 2008, Research priorities in the Tasmanian devil facial tumour debate, European Journal of Oncology, Vol 13(4), pp 229-238, p 231

119 Personal communication.

Figure 3:3 Different Strains of DFTD from different locations120

120 Pearse, 2011, Presentation to DPIPWE devil research team.

Figure 3:4 Devil Chromosomes 121

The images in Figure 3:4 above are accompanied by the following explanation. The figure

…compares a normal male karyotype with the karyotypes of 4 DFTD strains.

Anne-Maree Pearse (DPIPWE) has characterized at least 9 transmissible DFTD strains (A strain is defined as a karyotype of consistent chromosomal constituents that has been identified in multiple geographically proximate individuals and is therefore transmissible). Some interesting features of DFTD strains are emerging. Firstly, primary tumours appear highly stable, with little variation in chromosome numbers and conformations. Metastases are more variable karyotypically and contain variants exhibiting aneuploidy and aneusomy. These variants are not transmitted. There is also evidence that some strains are more successful than others – e.g. strain 2 has overtaken strain 1 as the most prominent strain. Tetraploid strain 1 has become more common than diploid strain 1. Some strains appear to have died out – e.g. strain 4 has only been seen in 5 individuals on the east coast. Tumour evolution also occurs in culture.122

121 Pyecroft, 2010, Internal DPIPWE Report

122 Pyecroft, 2010, Internal DPIPWE Report, p 43

The claim for transmission of DFTD appears to have narrowed to the highly stable primary tumours with variants unable to be transmitted. It also appears to be a deviation from CTVT where it was found that all tumours including primary, metastastic and cell cultures are similar as noted above. These observations also vary from the original claim made by Pearse and Swift in Nature –

…these anomalies were the same in the facial tumours of every animal (n=11).

These rearrangements are complex, but no intermediate stages were found between normal and tumour chromosomes, even in small primary cancers.123 The observations were not limited to those above but also included extreme instability as shown in the three images in Figure 3:5 below.

Figure 3:5 Images of DFTD chromosomes124

123 Pearse & Swift, 2006, p S49

124 Personal communication with Pearse, 2011, Presentation to DPIPWE devil research team.

Pearse proposed that the new theory of epigenetics, genetic changes due to environmental factors, may explain the different abnormalities in the different locations in the DFTD cells. 125 Pearse prepared a paper detailing her observations but she told me her original article was rejected by Cell.126 At the time of our meeting, she was in the process of re-writing it for submission to another journal. However, since then two articles with Pearse as a co-author have since been published.

The first was published in Cell and the second in PLoS Genetics, which appear to cover Pearse’s different strains. The Murchison et al article published in Cell in 2012 claims

‘[p]revious studies have indicated that the cancer is derived from the cells of one devil (the DFTD founder) and has subsequently spread through the devil population as a clone’ citing Pearse’s and Swift’s proposed hypothesis in Nature in 2006.127 In the discussion they state ‘[o]ur analysis of the genomes of two geographically distant DFTD subclones has indicated that DFTD is continuing to acquire new variations in its karyotype, genomic copy number and DNA sequence’.128 The second, Deakin et al’s

125 Personal communication on 18 March 2010 in Launceston

126 Animal Health Laboratories/Diagnostic Services Branch Deliverables to the STTDP, 2010, Notes on publications – Anne-Maree Pearse, Katherine Belov, Hannah V. Siddle, Kate Swift, Erin Noonan, Stephen Pyecroft and Mark D.B. Eldridge, Chromosome evoluation in Tasmanian Devil Facial Tumour Disease: a contagious cancer. Status Submitted, Rejected by Cell To be submitted to “Cancer Genetics and Cytogenetics”. p 22

127 Murchison EP, Schulz-Trieglaff OB, Ning Z, Alexandrov LD, Bauer MJ, Fu B, Hims M, Ding Z, Ivakhno S, Stewart C, Ng LB, Wong W, Aken B, White S, Alsop A, Becq J, Bignell GR, Cheetham RK, Cheng W, Connor TR, Cox AJ, Feng ZP, Gu Y, Crocock Rj, Harris SR, Khrebtukova I, Kingsbury Z, Kowarsky M, Dreiss A, Luo S, Marshall J, McBride, DJ, Murray L, Pearse AM, Raine K, Rasolonjatovo I, Shaw R, Tedder P, Tregidgo C, Vileila AJ, Wedge DC, Woods GM, Gormley N, Humphray S, Schroth G, Smith G, Hall, K, Searle SMJ, Carter NP, Papenfuss AT, Futreal PA, Campbell PJ, Yang F, Bentley DR, Evers DJ & Stratton MR, 2012, Genome Sequencing and Analysis of the Tasmanian Devil and Its Transmissible Cancer, Cell, Vol 148, pp 780-791, p 782

128 Murchison EP, Schulz-Trieglaff OB, Ning Z, Alexandrov LD, Bauer MJ, Fu B, Hims M, Ding Z, Ivakhno S, Stewart C, Ng LB, Wong W, Aken B, White S, Alsop A, Becq J, Bignell GR, Cheetham RK, Cheng W, Connor TR, Cox AJ, Feng ZP, Gu Y, Crocock Rj, Harris SR, Khrebtukova I, Kingsbury Z, Kowarsky M, Dreiss A, Luo S, Marshall J, McBride, DJ, Murray L, Pearse AM, Raine K, Rasolonjatovo I, Shaw R, Tedder P, Tregidgo C, Vileila AJ, Wedge DC, Woods GM, Gormley N, Humphray S, Schroth G, Smith G, Hall, K, Searle SMJ, Carter NP, Papenfuss AT, Futreal PA, Campbell PJ, Yang F, Bentley DR, Evers DJ & Stratton MR, 2012, Genome Sequencing and Analysis of the Tasmanian Devil and Its Transmissible Cancer, Cell, Vol 148, pp 780-791, p 787

2012 paper in PLoS Genetics again cites the Obendorf and McGlashan’s speculation from the Trowunna Wildlife Park claiming ‘[t]his observed pattern of intra-tumour chromosome variability is consistent with observations that the tumour is passed from animal to animal by biting, during which many clumps of tumour cells are dislodged from the mouth of the affected animal’. 129 Deakin et al conclude ‘[w]e provide further confirmation of the clonal transmission of DFTD and tentatively identify the sentinel animal as a female devil’.130 The editor of PLoS Genetics is Stephen J. O’Brien and the study was funded by the Australian Research Council, the Dr Eric Guiler Tasmanian Devil Research Grants and DPIPWE. Both articles claim that although it appears through G-banding that the chromosomes are unstable, chromosome painting and gene mapping show that the chromosomes remain stable. However, in undertaking these studies they did not identify, as Murgia et al did in CTVT, the marker gene to confirm DFTD like CTVT is transmissible.

Pearse’s initial observation conflicts with the now recognized different strains, as shown here in the Conservation Magazine:

When she stained the nuclei of tumour cells from several different devils, she saw that the chromosomes were abnormal. The “leg and arms” of the chromosomes looked as if they had been cut off and glued back together in arbitrary places. This was not too surprising; lots of tumor cells have rearrangements in their chromosomes. But what was surprising was that all the tumor cells, whether from one devil or another, had exactly the same rearrangements – the bizarre rearrangements were identical.131

129 Deakin JE, Bender HS, Pearse AM, Rens W, O’Brien PCM, Ferguson-Smith MA, Cheng Y, Morris K, Taylor R, Stuart A, Belov, K, Amemiya CT, Murchison, EP, Papenfuss AT & Graves JAM, 2012, PLoS Genetics, Vol 8(2), pp 1-16, p 13

130 ibid.

131 Mills C, 2008, Cancer on a Whole Species, The gruesome disease ravaging Tasmanian devils is unlike anything we’ve seen before, Conservation Magazine, Vol 9(1). Available at:

http://conservationmagazine.org/2008/07/cancer-on-a-whole-species/ last accessed 2 October 2013

The research into the different strains of cancer may be important but it has not provided proof that the cancer is contagious; in fact if anything, it has weakened the evidence. Instability is the hallmark of cancer.132