Horizontal Transmission of Clonal Cancer Cells Causes Leukemia in Soft-Shell Clams

Metzger, Michael J.; Reinisch, Carol L.; Sherry, James; Goff, Stephen P.

doi:10.1016/j.cell.2015.02.042

Cited by 212 publications

(256 citation statements)

References 43 publications

(63 reference statements)

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“…On the other hand, host selective adaptations towards higher tolerance to infection are expected to occur in long-term DFTD-affected populations. Transmissible cancers are rare (only three cases in nature: DFTD, emerged almost 20 years ago; CTVT, emerged at least 10 000 years ago [18]; and the recently emerged leukaemia-like cancer in soft-shell clams [17]), and there is much to learn about early and long-term selective pressures on virulence (reduction in host fitness) and malignancy (metastasis, genomic instability) that may be better explored within a genomic sequencing framework. Although we have found evidence for a DFTD lineage replacement at WPP that correlates with changing epidemic patterns, we cannot discount the possibility that host genetic or environmental factors may have influenced the tumour dynamics observed at our site.…”

Section: Discussionmentioning

confidence: 99%

“…Directly transmissible cancers, in which the pathogen is a clonal infectious cell line spread through injurious contact [14], are particularly rare in nature. They are known only in the recently emerged Tasmanian devil facial tumour disease (DFTD) [15], which threatens its unique host, the Tasmanian devil (Sarcophilus harrisii), with extinction [16], a leukaemia-type disease affecting soft-shell clams in North America [17], and the much older (approx. 11 000 years) and evolutionarily stable canine transmissible venereal tumour (CTVT) [18].…”

Section: Introductionmentioning

confidence: 99%

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Transmissible cancer in Tasmanian devils: localized lineage replacement and host population response

et al. 2015

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Tasmanian devil facial tumour disease (DFTD) is a clonally transmissible cancer threatening the Tasmanian devil (Sarcophilus harrisii) with extinction. Live cancer cells are the infectious agent, transmitted to new hosts when individuals bite each other. Over the 18 years since DFTD was first observed, distinct genetic and karyotypic sublineages have evolved. In this longitudinal study, we investigate the associations between tumour karyotype, epidemic patterns and host demographic response to the disease. Reduced host population effects and low DFTD infection rates were associated with high prevalence of tetraploid tumours. Subsequent replacement by a diploid variant of DFTD coincided with a rapid increase in disease prevalence, population decline and reduced mean age of the population. Our results suggest a role for tumour genetics in DFTD transmission dynamics and epidemic outcome. Future research, for this and other highly pathogenic emerging infectious diseases, should focus on understanding the evolution of host and pathogen genotypes, their effects on susceptibility and tolerance to infection, and their implications for designing novel genetic management strategies. This study provides evidence for a rapid localized lineage replacement occurring within a transmissible cancer epidemic and highlights the possibility that distinct DFTD genetic lineages may harbour traits that influence pathogen fitness.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Transmissible cancer in Tasmanian devils: localized lineage replacement and host population response

et al. 2015

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“…Metzger, Reinisch, Sherry, and Goff (2015) first reported a transmissible leukemia in the soft‐shell clam Mya arenaria . This result implied that malignant cells could survive the transit in seawater and managed to escape the more rudimentary self‐recognition system of this bivalve.…”

Section: Transmissible Cancers Might Be More Widespread Than Previousmentioning

confidence: 99%

Weird genotypes? Don't discard them, transmissible cancer could be an explanation

Riquet

Simon

Bierne

2016

Evolutionary Applications

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Genetic chimerism is rarely considered in the analysis of population genetics data, because assumed to be an exceptionally rare, mostly benign, developmental accident. An unappreciated source of chimerism is transmissible cancer, when malignant cells have become independent parasites and can infect other individuals. Parasitic cancers were thought to be rare exceptions, only reported in dogs (Murgia et al., Cell, 2006, 126, 477; Rebbeck et al., Evolution, 2009, 63, 2340), Tasmanian devils (Pearse and Swift, Nature, 2006, 439, 549; Pye et al., Proceedings of the National Academy of Sciences, 2016, 113, 374), and soft‐shell clams (Metzger et al., Cell, 2015, 161, 255). However, the recent simultaneous report of four new contagious leukemias in marine mollusks (Metzger et al., Nature, 2016, 534, 705) might change the rules. By doubling up the number of naturally occurring transmissible cancers, this discovery suggests they may essentially be missed because not sufficiently searched for, especially outside mammals. We encourage population geneticists to keep in mind infectious cancer when interpreting weird genotypes in their molecular data. It would then contribute in the investigation of how widespread contagious cancer could really be in the wild. We provide an example with our own data in Mytilus mussels, a commercially important shellfish. We identified genetic chimerism in a few mussels that suggests the possible occurrence at low prevalence in European M. edulis populations of a M. trossulus contagious cancer related to the one described by Metzger et al. (Nature, 2016, 534, 705) in populations of British Columbia.

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“…Only three transmissible cancers have been observed in nature, and these cause Tasmanian devil facial tumor disease (DFTD), canine transmissible venereal tumor (CTVT), and softshell clam disseminated neoplasia, respectively (1,2). Each of these clones originated in a "founder animal" whose somatic cells acquired changes that drove carcinogenesis as well as adaptations for transmission and long-term survival (3).…”

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confidence: 99%

A second transmissible cancer in Tasmanian devils

Pye

Pemberton²,

Tovar

et al. 2015

Proc. Natl. Acad. Sci. U.S.A.

205

328

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Clonally transmissible cancers are somatic cell lineages that are spread between individuals via the transfer of living cancer cells. There are only three known naturally occurring transmissible cancers, and these affect dogs, soft-shell clams, and Tasmanian devils, respectively. The Tasmanian devil transmissible facial cancer was first observed in 1996, and is threatening its host species with extinction. Until now, this disease has been consistently associated with a single aneuploid cancer cell lineage that we refer to as DFT1. Here we describe a second transmissible cancer, DFT2, in five devils located in southern Tasmania in 2014 and 2015. DFT2 causes facial tumors that are grossly indistinguishable but histologically distinct from those caused by DFT1. DFT2 bears no detectable cytogenetic similarity to DFT1 and carries a Y chromosome, which contrasts with the female origin of DFT1. DFT2 shows different alleles to both its hosts and DFT1 at microsatellite, structural variant, and major histocompatibility complex (MHC) loci, confirming that it is a second cancer that can be transmitted between devils as an allogeneic, MHC-discordant graft. These findings indicate that Tasmanian devils have spawned at least two distinct transmissible cancer lineages and suggest that transmissible cancers may arise more frequently in nature than previously considered. The discovery of DFT2 presents important challenges for the conservation of Tasmanian devils and raises the possibility that this species is particularly prone to the emergence of transmissible cancers. More generally, our findings highlight the potential for cancer cells to depart from their hosts and become dangerous transmissible pathogens.

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Horizontal Transmission of Clonal Cancer Cells Causes Leukemia in Soft-Shell Clams

Cited by 212 publications

References 43 publications

Transmissible cancer in Tasmanian devils: localized lineage replacement and host population response

Transmissible cancer in Tasmanian devils: localized lineage replacement and host population response

Weird genotypes? Don't discard them, transmissible cancer could be an explanation

A second transmissible cancer in Tasmanian devils

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