The cancer which survived: insights from the genome of an 11000 year-old cancer

Strakova, Andrea; Murchison, Elizabeth P.

doi:10.1016/j.gde.2015.03.005

Cited by 52 publications

(64 citation statements)

References 51 publications

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“…Analysis of mtDNA in 37 transmissible venereal tumors in dogs and comparable mtDNA regions from 15 host animals and 43 published canine mtDNA sequences suggested that these tumors have periodically acquired mitochondria from their hosts, perhaps over a period of 11,000 years since this tumor originated (16,17). It has been estimated that transfer of mitochondria into malignant cells with heavily mutated mtDNA occurs once in about 100 years.…”

Section: In Vivo Studiesmentioning

confidence: 99%

“…Since then, considerable in vitro evidence has confirmed organelle transfer, including mitochondria, to and between tumor cells (2)(3)(4)(5)(6)(7)(8) as well as between nontumor cells (9)(10)(11)(12)(13)(14)(15). Additionally, recent phylogenetic evidence suggests that mtDNA can "move" between normal cells and tumor cells in canine venereal transmissible cancer (16,17), while pathophysiological models of lung injury (18,19), lung inflammation (19), and tumor formation by respiration-deficient tumor cells (19) have added weight to intercellular mitochondrial transfer being a new (patho) physiological phenomenon.…”

Section: Introductionmentioning

confidence: 99%

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Mitochondrial DNA in Tumor Initiation, Progression, and Metastasis: Role of Horizontal mtDNA Transfer

2015

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Mitochondrial DNA (mtDNA), encoding 13 out of more than 1,000 proteins of the mitochondrial proteome, is of paramount importance for the bioenergetic machinery of oxidative phosphorylation that is required for tumor initiation, propagation, and metastasis. In stark contrast to the widely held view that mitochondria and mtDNA are retained and propagated within somatic cells of higher organisms, recent in vitro and in vivo evidence demonstrates that mitochondria move between mammalian cells. This is particularly evident in cancer where defective mitochondrial respiration can be restored and tumor-forming ability regained by mitochondrial acquisition. This paradigm shift in cancer cell biology and mitochondrial genetics, concerning mitochondrial movement between cells to meet bioenergetic needs, not only adds another layer of plasticity to the armory of cancer cells to correct damaged mitochondria, but also points to potentially new therapeutic approaches. Cancer Res; 75(16); 3203-8. Ó2015AACR.

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Section: In Vivo Studiesmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Mitochondrial DNA in Tumor Initiation, Progression, and Metastasis: Role of Horizontal mtDNA Transfer

2015

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“…It was first studied in 1876 by Novinsky and later by Smith & Washbourn (Marchal et al 1997, Rogers 1997, MacEwen 2001, Oliveira et al 2013. Since that time, TVT has been described as a transmissible and transplantable tumor (Booth 1994, Hasler & Weber 2000, Rebbeck et al 2009, Strakova & Murchison 2015. This neoplasm has spread in dogs worldwide, but a major prevalence is located in tropical and subtropical climates (Ferreira et al 2000, Varaschin et al 2001, mainly in countries with large populations of mongrel street dogs (Papazoglou et al 2001, Strakova & Murchison 2014.…”

Section: Introductionmentioning

confidence: 99%

Immunocytochemical characterization of primary cell culture in canine transmissible venereal tumor

et al. 2016

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RESUMO.-[Caracterização imunocitoquímica de culturas primárias de tumor venéreo transmissível canino.]Os anticorpos anti-vimentina, anti-lisozima, anti-alfa 1 antitripsina, anti-CD3 e anti-CD79α foram empregados para a caracterização de culturas primárias de tumor venéreo transmissível canino (TVT). Amostras para cultura primá-ria e imuno-histoquímica foram coletadas de oito cães com diagnóstico clínico e citológico de TVT. Para validar o resultado inmunocitoquímico nas culturas de TVT foi realizada a contagem de cromossomos. Para a análise estatística o teste de Mann-Whitney foi empregado a um nível de significância de p<0.05. As culturas e os tecidos de TVT apresentaram intensa reatividade para vimentina, moderada a leve para Lisozima, moderada para alfa-antitripsina e não houve marcação para CD3 e CD79α. Immunochemistry with anti-vimentin, anti-lysozyme, anti-alpha 1 antitrypsin, anti-CD3 and anti-CD79α antibodies has been used for characterization of primary cell culture in the transmissible venereal tumor (TVT). Samples for primary cell culture and immunohistochemistry assays were taken from eight dogs with cytological and clinical diagnosis of TVT. To validate the immunochemical results in the primary cell culture of TVT, a chromosome count was performed. For the statistical analysis, the Mann-Whitney test with p<0.05 was used. TVT tissues and culture cells showed intense anti-vimentin immunoreactivity, lightly to moderate immunoreactivity for anti-lysozyme, and mild for anti-alpha-antitrypsin. No marking was achieved for CD3 and CD79α. All culture cells showed chromosomes variable number of 56 to 68. This is the first report on the use of immunocytochemical characterization in cell culture of TVT. Significant statistic difference between immunochemistry in tissue and culture cell was not established, what suggests that the use of this technique may provide greater certainty for the confirmation of tumors in the primary culture. This fact is particularly important because in vitro culture of tumor tissues has been increasingly used to provide quick access to drug efficacy and presents relevant information to identify potential response to anticancer medicine; so it is possible to understand the behavior of the tumor. Immunocytochemical characterization of primary cell culture in transmissible venereal tumor o uso da immunocitoquímica para a caracterização de culturas de TVT. Assim, e devido ao fato de se observar semelhança entre a imunomarcação em células e tecidos, sugere-se que o uso desta técnica possa auxiliar na confirmação de culturas primárias do tumor, fato muito importante porque a utilização da cultura do tumor pode permitir o acesso a informação relevante sobre resposta potencial a um tratamento e conhecimento do comportamento biológico do tumor.TERMOS DE INDEXAÇÃO: Tumor venéreo transmissível canino, alfa 1 antitripsina, citogenética, lisozima, vimentina.

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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). The rarity of transmissible cancer lineages in nature, despite the ubiquity of cancers that remain in one individual, suggests that the emergence of such clones is extraordinarily improbable.…”

mentioning

confidence: 99%

A second transmissible cancer in Tasmanian devils

Pye

Pemberton²,

Tovar

et al. 2015

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

204

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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The cancer which survived: insights from the genome of an 11000 year-old cancer

Cited by 52 publications

References 51 publications

Mitochondrial DNA in Tumor Initiation, Progression, and Metastasis: Role of Horizontal mtDNA Transfer

Mitochondrial DNA in Tumor Initiation, Progression, and Metastasis: Role of Horizontal mtDNA Transfer

Immunocytochemical characterization of primary cell culture in canine transmissible venereal tumor

A second transmissible cancer in Tasmanian devils

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