Telomere dynamics and homeostasis in a transmissible cancer

Devil Facial Tumour Disease (DFTD) is a unique clonal cancer that threatens the world\u27s largest carnivorous marsupial, the Tasmanian devil (Sarcophilus harrisii) with extinction. This transmissible cancer is passed between individual devils by cell implantation during social interactions. The tumour arose in a Schwann cell of a single devil over 15 years ago and since then has expanded clonally, without showing signs of replicative senescence; in stark contrast to a somatic cell that displays a finite capacity for replication, known as the “Hayflick limit”

Supplementation of Nucleotides to Enhance Performance and Immune Responses of Asian Seabass

Supplementation of nucleotides into fish diets can be an alternative method to manage disease problems in aquaculture, since it was reported could improve the growth rate and immunity of some aquaculture species. The present study assessed the growth and immune performance of Asian seabass (Lates calcarifer Bloch 1790) after being fed diets containing different levels of a commercial nucleotide (Optimun®) and a purified mixture of nucleotides containing AMP (Adenosine monophosphate), IMP (Inosine monophosphate), UMP (Uridine monophosphate), GMP (Guanidine monophosphate) and CMP (Cytidine monophosphate) in equal amounts. Six nucleotide supplemented diets and a control diet were used in this study, namely O1 (Optimun® 0.25 %), O2 (Optimun® 0.5 %), O3 (Optimun® 0.75 %), P1 (0.25 % mixed pure nucleotides), P2 (0.5 % mixed pure nucleotides), P3 (0.75 % mixed pure nucleotide) and C (control/diet without nucleotide supplementation). The treatment diets were fed to juvenile Asian seabass (average initial weight of 13.19 g ± 0.58 g) at 3 % body weight per day for six weeks. The results showed that weight gain, total serum protein and globulin were significantly higher in fish fed diet P2 (0.5 % of a mix pure nucleotides) compared to the control group (P 0.05). In conclusion, supplementation of nucleotides in Asian seabass diet may have positive effect on growth performance and immune response of the fish, while diet containing 0.5% of mixed pure nucleotides tend to have a better result compared to other diet groups

Supplementation of Nucleotides to Enhance Performance and Immune Responses of Asian Seabass

Supplementation of nucleotides into fish diets can be an alternative method to manage disease problems in aquaculture, since it was reported could improve the growth rate and immunity of some aquaculture species. The present study assessed the growth and immune performance of Asian seabass (Lates calcarifer Bloch 1790) after being fed diets containing different levels of a commercial nucleotide (Optimun®) and a purified mixture of nucleotides containing AMP (Adenosine monophosphate), IMP (Inosine monophosphate), UMP (Uridine monophosphate), GMP (Guanidine monophosphate) and CMP (Cytidine monophosphate) in equal amounts. Six nucleotide supplemented diets and a control diet were used in this study, namely O1 (Optimun® 0.25 %), O2 (Optimun® 0.5 %), O3 (Optimun® 0.75 %), P1 (0.25 % mixed pure nucleotides), P2 (0.5 % mixed pure nucleotides), P3 (0.75 % mixed pure nucleotide) and C (control/diet without nucleotide supplementation). The treatment diets were fed to juvenile Asian seabass (average initial weight of 13.19 g ± 0.58 g) at 3 % body weight per day for six weeks. The results showed that weight gain, total serum protein and globulin were significantly higher in fish fed diet P2 (0.5 % of a mix pure nucleotides) compared to the control group (P 0.05). In conclusion, supplementation of nucleotides in Asian seabass diet may have positive effect on growth performance and immune response of the fish, while diet containing 0.5% of mixed pure nucleotides tend to have a better result compared to other diet groups

Devil Facial Tumor Disease, A Potential Model of the Cancer Stem-Cell Process?

Tasmanian devil facial tumor disease (DFTD) is a naturally occurring contagious cancer which is transmitted as a clonal cell line between devils. The malignant cell line evolved from a Schwann cell or precursor prior to 1996 and since then has undergone continuous division without exhausting its replicative potential, suggesting a profound capacity for self renewal. It is therefore important to elucidate whether DFTD may have a stem cell origin. Deciphering the pathways regulating DFT cell proliferation and survival could lead to increased understanding of this transimissible cancer and to the development of successful therapies to halt the disease. We investigated whether DFT cells have originated from transformed stem cells by measuring the expression levels of thirteen genes characteristic to embryonic stem and/or pluripotent germ cells. No differences in gene expression were observed between DFT cells and peripheral nerve controls, and therefore our results provide additional support for Schwann cell or peripheral nerve origin of DFTD. Although our dataset is preliminary, it does not suggest that DFTs have cancer stem cells (CSCs) origin. We provide details of further experiments needed to ultimately confirm the role of cancer stem cells in DFTD progression

Anthropogenic selection enhances cancer evolution in Tasmanian devil tumours

The Tasmanian Devil Facial Tumour Disease (DFTD) provides a unique opportunity to elucidate the long-term effects of natural and anthropogenic selection on cancer evolution. Since first observed in 1996, this transmissible cancer has caused local population declines by >90%. So far, four chromosomal DFTD variants (strains) have been described and karyotypic analyses of 253 tumours showed higher levels of tetraploidy in the oldest strain. We propose that increased ploidy in the oldest strain may have evolved in response to effects of genomic decay observed in asexually reproducing organisms. In this study, we focus on the evolutionary response of DFTD to a disease suppression trial. Tumours collected from devils subjected to the removal programme showed accelerated temporal evolution of tetraploidy compared with tumours from other populations where no increase in tetraploid tumours were observed. As ploidy significantly reduces tumour growth rate, we suggest that the disease suppression trial resulted in selection favouring slower growing tumours mediated by an increased level of tetraploidy. Our study reveals that DFTD has the capacity to rapidly respond to novel selective regimes and that disease eradication may result in novel tumour adaptations, which may further imperil the long-term survival of the world\u27s largest carnivorous marsupial

Genomic Restructuring in the Tasmanian Devil Facial Tumour: Chromosome Painting and Gene Mapping Provide Clues to Evolution of a Transmissible Tumour

Devil facial tumour disease (DFTD) is a fatal, transmissible malignancy that threatens the world's largest marsupial carnivore, the Tasmanian devil, with extinction. First recognised in 1996, DFTD has had a catastrophic effect on wild devil numbers, and intense research efforts to understand and contain the disease have since demonstrated that the tumour is a clonal cell line transmitted by allograft. We used chromosome painting and gene mapping to deconstruct the DFTD karyotype and determine the chromosome and gene rearrangements involved in carcinogenesis. Chromosome painting on three different DFTD tumour strains determined the origins of marker chromosomes and provided a general overview of the rearrangement in DFTD karyotypes. Mapping of 105 BAC clones by fluorescence in situ hybridisation provided a finer level of resolution of genome rearrangements in DFTD strains. Our findings demonstrate that only limited regions of the genome, mainly chromosomes 1 and X, are rearranged in DFTD. Regions rearranged in DFTD are also highly rearranged between different marsupials. Differences between strains are limited, reflecting the unusually stable nature of DFTD. Finally, our detailed maps of both the devil and tumour karyotypes provide a physical framework for future genomic investigations into DFTD

Evolution of a contagious cancer: epigenetic variation in devil facial tumour disease

The emergence of Devil Facial Tumour Disease (DFTD), a highly contagious cancer, is driving Tasmanian devils (Sarcophilus harrisii) to extinction. The cancer is a genetically and chromosomally stable clonal cell line which is transmitted by biting during social interactions. In the present study, we explore the Devil Facial Tumour (DFT) epigenome and the genes involved in DNA methylation homeostasis. We show that tumour cells have similar levels of methylation to peripheral nerves, the tissue from which DFTD originated. We did not observe any strain or region-specific epimutations. However, we revealed a significant increase in hypomethylation in DFT samples over time (p < 0.0001). We propose that loss of methylation is not because of a maintenance deficiency, as an upregulation of DNA methyltransferase 1 gene was observed in tumours compared with nerves (p < 0.005). Instead, we believe that loss of methylation is owing to active demethylation, supported by the temporal increase in MBD2 and MBD4 (p < 0.001). The implications of these changes on disease phenotypes need to be explored. Our work shows that DFTD should not be treated as a static entity, but rather as an evolving parasite with epigenetic plasticity. Understanding the role of epimutations in the evolution of this parasitic cancer will provide unique insights into the role of epigenetic plasticity in cancer evolution and progression in traditional cancers that arise and die with their hosts

Data from: Anthropogenic selection enhances cancer evolution in Tasmanian devil tumours

The Tasmanian Devil Facial Tumour Disease (DFTD) provides a unique opportunity to elucidate the long-term effects of natural and anthropogenic selection on cancer evolution. Since first observed in 1996, this transmissible cancer has caused local population declines by >90%. So far, four chromosomal DFTD variants (strains) have been described and karyotypic analyses of 253 tumours showed higher levels of tetraploidy in the oldest strain. We propose that increased ploidy in the oldest strain may have evolved in response to effects of genomic decay observed in asexually reproducing organisms. In this study, we focus on the evolutionary response of DFTD to a disease suppression trial. Tumours collected from devils subjected to the removal programme showed accelerated temporal evolution of tetraploidy compared with tumours from other populations where no increase in tetraploid tumours were observed. As ploidy significantly reduces tumour growth rate, we suggest that the disease suppression trial resulted in selection favouring slower growing tumours mediated by an increased level of tetraploidy. Our study reveals that DFTD has the capacity to rapidly respond to novel selective regimes and that disease eradication may result in novel tumour adaptations, which may further imperil the long-term survival of the world's largest carnivorous marsupial