Evolution and lineage dynamics of a transmissible cancer in Tasmanian devils

Kwon, Young Mi; Gori, Kevin; Park, Naomi; Potts, Nicole; Swift, Kate; Wang, Jinhong; Stammnitz, Maximilian R; Cannell, Naomi; Baez‐Ortega, Adrian; Comte, Sébastien; Fox, Samantha; Harmsen, Colette; Huxtable, Stewart J.; Jones, Menna Lloyd; Kreiss, Alexandre; Lawrence, C.C.; Lazenby, Billie; Peck, Sarah; Pye, Ruth J.; Woods, Gregory M.; Zimmermann, Mona; Wedge, David C.; Pemberton, David; Stratton, Michael R.; Hamede, Rodrigo; Murchison, Elizabeth P.

doi:10.1371/journal.pbio.3000926

Cited by 27 publications

(66 citation statements)

References 60 publications

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“…We surprisingly observed a high amount of nuclear and mitochondrial polymorphism in MtrBTN2 samples. This polymorphism defines two sublineages that co-exist and spread in the same populations, as it has been observed in other transmissible cancers (CTVT: Baez-Ortega et al 2019, DFTD: Kwon et al 2020, Patton et al 2020.…”

Section: Discussionmentioning

confidence: 72%

Prevalence and polymorphism of a mussel transmissible cancer in Europe

et al. 2021

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Transmissible cancers are parasitic malignant cell lineages that acquired the ability to infect new hosts from the same species, or sometimes related species. First described in dogs and Tasmanian devils, transmissible cancers were later discovered in some marine bivalves affected by a leukemia-like disease. In Mytilus mussels, two lineages of Bivalve Transmissible Neoplasia (BTN) have been described to date (MtrBTN1 and MtrBTN2), both emerged in a M. trossulus founder individual. Here, we performed an extensive screening of genetic chimerism, a hallmark of transmissible cancer, by genotyping 106 SNPs of 5907 European Mytilus mussels. The genetic analysis allowed us to simultaneously obtain the genotype of hosts -M. edulis, M. galloprovincialis or hybrids -and the genotype of tumors of heavily infected individuals. In addition, a subset of 222 individuals were systematically genotyped and analysed by histology in order to screen for possible non-transmissible cancers. We detected MtrBTN2 at low prevalence in M.edulis, and also in M. galloprovincialis and hybrids although at a much lower prevalence. No MtrBTN1 or new BTN were found, but 8 individuals with non-transmissible neoplasia were observed at a single polluted site on the same sampling date. We observed a diversity of MtrBTN2 genotypes that appeared more introgressed or more ancestral than MtrBTN1 and reference healthy M. trossulus individuals. The observed polymorphism is most likely due to somatic null alleles caused by structural variations or point mutations in primer-binding sites leading to enhanced detection of the host alleles. Despite low prevalence, two sublineages divergent by 10% fixed somatic null alleles and one non-synonymous mtCOI substitution, are co-spreading in the same geographic area, suggesting a complex diversification of MtrBTN2 since its emergence and host species shift.

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Section: Discussionmentioning

confidence: 72%

Prevalence and polymorphism of a mussel transmissible cancer in Europe

et al. 2021

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“…Given that we analysed only 76 nucleotide positions and that the mtCOI divergence is not very strong, we believe polymorphism observed among tumors could more likely be due to structural rather than point variations, such as insertion-deletion and chromosomal losses or gains, or recombination leading to loss of heterozygosity, that are widespread in cancer (McClelland 2017, Nichols et al 2020 and have been reported in other transmissible cancers (e.g. in DFT1 and DFT2, Kwon et al 2020). According to the genotyping method used (competition of the two allele fluorescences), partial or complete chromosomal losses or gains results in a modification of the ratio of fluorescences of the two alleles of hyperploid MtrBTN2 tumors and of the ratio of tumor and host genotypes.…”

Section: Discussionmentioning

confidence: 99%

“…In Tasmanian devils two independent transmissible cancers lineages have emerged in the last 30 years. In bother cases, although at different spatiotemporal scales, genome studies have shown early diversification into sublineages and secondary co-existence of some divergent sublineages (Baez-Ortega et al 2019, Kwon et al 2020Patton et al 2020). Studies in marine bivalves also showed multiple emergences (two in Cerastoderma edule, Metzger et al 2016 and two in Mytilus trossulus, Yonemitsu et al 2019) and for the first time in transmissible cancer research, transmissions crossing the species barrier (BTN lineage in Polititapes aureus has a Venerupis corrugata origin, Metzger et al 2016, and MtrBTN2 in M. edulis and M. chilensis has a M. trossulus origin, Yonemitsu et al 2019).…”

Section: Introductionmentioning

confidence: 99%

Prevalence and polymorphism of a mussel transmissible cancer in Europe

Hammel

Simon

Arbiol

et al. 2021

Preprint

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Transmissible cancers are parasitic malignant cell lineages that acquired the ability to infect new hosts from the same species, or sometimes related species. First described in dogs and Tasmanian devils, transmissible cancers were later discovered in some marine bivalves affected by a leukemia-like disease. In Mytilus mussels, two lineages of Bivalve Transmissible Neoplasia (BTN), both emerged in a M. trossulus founder individual, have been described to date (MtrBTN1 and MtrBTN2). Here, we performed an extensive screening of genetic chimerism, a hallmark of transmissible cancer, by genotyping hundred SNPs of thousands of European Mytilus mussels. The genetic analysis allowed us to simultaneously obtain the genotype of hosts -M. edulis, M. galloprovincialis or hybrids- and the genotype of tumors of heavily infected individuals. In addition, a subset of individuals were systematically genotyped and analysed by histology in order to screen for possible non-transmissible cancers. We detected MtrBTN2 at low prevalence in M. edulis, and also in M. galloprovincialis and hybrids although at a much lower prevalence. No MtrBTN1 or new BTN were found but a few individuals with non-transmissible neoplasia were observed at a single polluted site on the same sampling date. We observed a diversity of MtrBTN2 genotypes that appeared more introgressed or more ancestral than MtrBTN1 and reference healthy M. trossulus individuals. The observed polymorphism is most likely due to somatic null alleles caused by structural variations or point mutations in primer-binding sites leading to enhanced detection of the host alleles. Despite low prevalence, two divergent sublineages, confirmed by mtCOI sequences, are co-spreading in the same geographic area, suggesting a complex diversification of MtrBTN2 since its emergence and host species shift.

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“…A major difference between non-communicable cancers and transmissible cancers is that classical cancer cells have to ‘reinvent the wheel’ at every step – from initiation and progression to metastasis, but ultimately, they all die with the death of the host. In contrast, in transmissible cancers, clonal cell lineages are passed from host to host, and thus evolve as novel parasitic life forms, as seen in CTVT and DFTD, where these cancer lineages have continued to evolve since their initial emergence ( Pearse et al, 2012 ; Dujon et al, 2020a ; Kwon et al, 2020 ). Thus, investigating whether the tumoral GPC has been adjusted by selection in a way that optimizes the parasitic lifestyle will also provide insight into the evolution of parasitism.…”

Section: Group Phenotypic Composition In the Context Of Cancermentioning

confidence: 99%

Group phenotypic composition in cancer

Capp

DeGregori

Nedelcu

et al. 2021

eLife

Self Cite

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Although individual cancer cells are generally considered the Darwinian units of selection in malignant populations, they frequently act as members of groups where fitness of the group cannot be reduced to the average fitness of individual group members. A growing body of studies reveals limitations of reductionist approaches to explaining biological and clinical observations. For example, induction of angiogenesis, inhibition of the immune system, and niche engineering through environmental acidification and/or remodeling of extracellular matrix cannot be achieved by single tumor cells and require collective actions of groups of cells. Success or failure of such group activities depends on the phenotypic makeup of the individual group members. Conversely, these group activities affect the fitness of individual members of the group, ultimately affecting the composition of the group. This phenomenon, where phenotypic makeup of individual group members impacts the fitness of both members and groups, has been captured in the term ‘group phenotypic composition’ (GPC). We provide examples where considerations of GPC could help in understanding the evolution and clinical progression of cancers and argue that use of the GPC framework can facilitate new insights into cancer biology and assist with the development of new therapeutic strategies.

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Evolution and lineage dynamics of a transmissible cancer in Tasmanian devils

Cited by 27 publications

References 60 publications

Prevalence and polymorphism of a mussel transmissible cancer in Europe

Prevalence and polymorphism of a mussel transmissible cancer in Europe

Prevalence and polymorphism of a mussel transmissible cancer in Europe

Group phenotypic composition in cancer

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