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1. Bridging clinic and wildlife care with AI-powered pan-species computational pathology

Author

AbdulJabbar, Khalid, Castillo, Simon P, Hughes, Katherine, Davidson, Hannah, Boddy, Amy M, Abegglen, Lisa M, Minoli, Lucia, Iussich, Selina, Murchison, Elizabeth P, Graham, Trevor A, Spiro, Simon, Maley, Carlo C, Aresu, Luca, Palmieri, Chiara, and Yuan, Yinyin

Subjects
Biological Sciences, Biomedical and Clinical Sciences, Oncology and Carcinogenesis, Cancer, Life on Land, Male, Animals, Humans, Dogs, Animals, Wild, Artificial Intelligence, Prostatic Neoplasms, Neural Networks, Computer, Pan troglodytes
Abstract

Cancers occur across species. Understanding what is consistent and varies across species can provide new insights into cancer initiation and evolution, with significant implications for animal welfare and wildlife conservation. We build a pan-species cancer digital pathology atlas (panspecies.ai) and conduct a pan-species study of computational comparative pathology using a supervised convolutional neural network algorithm trained on human samples. The artificial intelligence algorithm achieves high accuracy in measuring immune response through single-cell classification for two transmissible cancers (canine transmissible venereal tumour, 0.94; Tasmanian devil facial tumour disease, 0.88). In 18 other vertebrate species (mammalia = 11, reptilia = 4, aves = 2, and amphibia = 1), accuracy (range 0.57-0.94) is influenced by cell morphological similarity preserved across different taxonomic groups, tumour sites, and variations in the immune compartment. Furthermore, a spatial immune score based on artificial intelligence and spatial statistics is associated with prognosis in canine melanoma and prostate tumours. A metric, named morphospace overlap, is developed to guide veterinary pathologists towards rational deployment of this technology on new samples. This study provides the foundation and guidelines for transferring artificial intelligence technologies to veterinary pathology based on understanding of morphological conservation, which could vastly accelerate developments in veterinary medicine and comparative oncology.

Published
2023

3. Somatic mutation rates scale with lifespan across mammals

Author

Cagan, Alex, Baez-Ortega, Adrian, Brzozowska, Natalia, Abascal, Federico, Coorens, Tim H. H., Sanders, Mathijs A., Lawson, Andrew R. J., Harvey, Luke M. R., Bhosle, Shriram, Jones, David, Alcantara, Raul E., Butler, Timothy M., Hooks, Yvette, Roberts, Kirsty, Anderson, Elizabeth, Lunn, Sharna, Flach, Edmund, Spiro, Simon, Januszczak, Inez, Wrigglesworth, Ethan, Jenkins, Hannah, Dallas, Tilly, Masters, Nic, Perkins, Matthew W., Deaville, Robert, Druce, Megan, Bogeska, Ruzhica, Milsom, Michael D., Neumann, Björn, Gorman, Frank, Constantino-Casas, Fernando, Peachey, Laura, Bochynska, Diana, Smith, Ewan St. John, Gerstung, Moritz, Campbell, Peter J., Murchison, Elizabeth P., Stratton, Michael R., and Martincorena, Iñigo

Published
2022
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4. Cross-species genomic landscape comparison of human mucosal melanoma with canine oral and equine melanoma.

Author

Wong, Kim, van der Weyden, Louise, Schott, Courtney R, Foote, Alastair, Constantino-Casas, Fernando, Smith, Sionagh, Dobson, Jane M, Murchison, Elizabeth P, Wu, Hong, Yeh, Iwei, Fullen, Douglas R, Joseph, Nancy, Bastian, Boris C, Patel, Rajiv M, Martincorena, Inigo, Robles-Espinoza, Carla Daniela, Iyer, Vivek, Kuijjer, Marieke L, Arends, Mark J, Brenn, Thomas, Harms, Paul W, Wood, Geoffrey A, and Adams, David J

Subjects
Mucous Membrane, Animals, Dogs, Horses, Humans, Melanoma, Mouth Neoplasms, Skin Neoplasms, Neoplasm Recurrence, Local, GTP Phosphohydrolases, Protein-Serine-Threonine Kinases, Cell Cycle Proteins, Microtubule-Associated Proteins, Cadherins, Membrane Proteins, Neoplasm Proteins, Tumor Suppressor Proteins, BRCA1 Protein, BRCA2 Protein, Species Specificity, Gene Expression Regulation, Neoplastic, Germ-Line Mutation, Tumor Suppressor Protein p53, PTEN Phosphohydrolase, Proto-Oncogene Proteins c-mdm2, Receptor-Like Protein Tyrosine Phosphatases, Class 3, DNA Copy Number Variations, Carcinogenesis, Gene Expression Regulation, Neoplastic, Neoplasm Recurrence, Local, Receptor-Like Protein Tyrosine Phosphatases, Class 3
Abstract

Mucosal melanoma is a rare and poorly characterized subtype of human melanoma. Here we perform a cross-species analysis by sequencing tumor-germline pairs from 46 primary human muscosal, 65 primary canine oral and 28 primary equine melanoma cases from mucosal sites. Analysis of these data reveals recurrently mutated driver genes shared between species such as NRAS, FAT4, PTPRJ, TP53 and PTEN, and pathogenic germline alleles of BRCA1, BRCA2 and TP53. We identify a UV mutation signature in a small number of samples, including human cases from the lip and nasal mucosa. A cross-species comparative analysis of recurrent copy number alterations identifies several candidate drivers including MDM2, B2M, KNSTRN and BUB1B. Comparison of somatic mutations in recurrences and metastases to those in the primary tumor suggests pervasive intra-tumor heterogeneity. Collectively, these studies suggest a convergence of some genetic changes in mucosal melanomas between species but also distinctly different paths to tumorigenesis.

Published
2019

5. Molecular characterization of a marine turtle tumor epizootic, profiling external, internal and postsurgical regrowth tumors

Author

Yetsko, Kelsey, Farrell, Jessica A., Blackburn, Nicholas B., Whitmore, Liam, Stammnitz, Maximilian R., Whilde, Jenny, Eastman, Catherine B., Ramia, Devon Rollinson, Thomas, Rachel, Krstic, Aleksandar, Linser, Paul, Creer, Simon, Carvalho, Gary, Devlin, Mariana A., Nahvi, Nina, Leandro, Ana Cristina, deMaar, Thomas W., Burkhalter, Brooke, Murchison, Elizabeth P., Schnitzler, Christine, and Duffy, David J.

Published
2021
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7. The evolutionary history of dogs in the Americas

Author

Leathlobhair, Máire Ní, Perri, Angela R., Irving-Pease, Evan K., Witt, Kelsey E., Linderholm, Anna, Haile, James, Lebrasseur, Ophelie, Ameen, Carly, Blick, Jeffrey, Boyko, Adam R., Brace, Selina, Cortes, Yahaira Nunes, Crockford, Susan J., Devault, Alison, Dimopoulos, Evangelos A., Eldridge, Morley, Enk, Jacob, Gopalakrishnan, Shyam, Gori, Kevin, Grimes, Vaughan, Guiry, Eric, Hansen, Anders J., Hulme-Beaman, Ardern, Johnson, John, Kitchen, Andrew, Kasparov, Aleksei K., Kwon, Young-Mi, Nikolskiy, Pavel A., Lope, Carlos Peraza, Manin, Aurélie, Martin, Terrance, Meyer, Michael, Myers, Kelsey Noack, Omura, Mark, Rouillard, Jean-Marie, Pavlova, Elena Y., Sciulli, Paul, Sinding, Mikkel-Holger S., Strakova, Andrea, Ivanova, Varvara V., Widga, Christopher, Willerslev, Eske, Pitulko, Vladimir V., Barnes, Ian, Gilbert, M. Thomas P., Dobney, Keith M., Malhi, Ripan S., Murchison, Elizabeth P., Larson, Greger, and Frantz, Laurent A. F.

Published
2018

10. The evolution of two transmissible cancers in Tasmanian devils

Author

Stammnitz, Maximilian R., primary, Gori, Kevin, additional, Kwon, Young Mi, additional, Harry, Edward, additional, Martin, Fergal J., additional, Billis, Konstantinos, additional, Cheng, Yuanyuan, additional, Baez-Ortega, Adrian, additional, Chow, William, additional, Comte, Sebastien, additional, Eggertsson, Hannes, additional, Fox, Samantha, additional, Hamede, Rodrigo, additional, Jones, Menna, additional, Lazenby, Billie, additional, Peck, Sarah, additional, Pye, Ruth, additional, Quail, Michael A., additional, Swift, Kate, additional, Wang, Jinhong, additional, Wood, Jonathan, additional, Howe, Kerstin, additional, Stratton, Michael R., additional, Ning, Zemin, additional, and Murchison, Elizabeth P., additional

Published
2023
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11. Recurrent horizontal transfer identifies mitochondrial positive selection in a transmissible cancer

Author

Strakova, Andrea, Nicholls, Thomas J., Baez-Ortega, Adrian, Ní Leathlobhair, Máire, Sampson, Alexander T., Hughes, Katherine, Bolton, Isobelle A. G., Gori, Kevin, Wang, Jinhong, Airikkala-Otter, Ilona, Allen, Janice L., Allum, Karen M., Arnold, Clara L., Bansse-Issa, Leontine, Bhutia, Thinlay N., Bisson, Jocelyn L., Blank, Kelli, Briceño, Cristóbal, Castillo Domracheva, Artemio, Corrigan, Anne M., Cran, Hugh R., Crawford, Jane T., Cutter, Stephen M., Davis, Eric, de Castro, Karina F., De Nardi, Andrigo B., de Vos, Anna P., Delgadillo Keenan, Laura, Donelan, Edward M., Espinoza Huerta, Adela R., Faramade, Ibikunle A., Fazil, Mohammed, Fotopoulou, Eleni, Fruean, Skye N., Gallardo-Arrieta, Fanny, Glebova, Olga, Gouletsou, Pagona G., Häfelin Manrique, Rodrigo F., Henriques, Joaquim J. G. P., Horta, Rodrigo S., Ignatenko, Natalia, Kane, Yaghouba, King, Cathy, Koenig, Debbie, Krupa, Ada, Kruzeniski, Steven J., Lanza-Perea, Marta, Lazyan, Mihran, Lopez Quintana, Adriana M., Losfelt, Thibault, Marino, Gabriele, Martínez Castañeda, Simón, Martínez-López, Mayra F., Masuruli, Bedan M., Meyer, Michael, Migneco, Edward J., Nakanwagi, Berna, Neal, Karter B., Neunzig, Winifred, Nixon, Sally J., Ortega-Pacheco, Antonio, Pedraza-Ordoñez, Francisco, Peleteiro, Maria C., Polak, Katherine, Pye, Ruth J., Ramirez-Ante, Juan C., Reece, John F., Rojas Gutierrez, Jose, Sadia, Haleema, Schmeling, Sheila K., Shamanova, Olga, Sherlock, Alan G., Steenland-Smit, Audrey E., Svitich, Alla, Tapia Martínez, Lester J., Thoya Ngoka, Ismail, Torres, Cristian G., Tudor, Elizabeth M., van der Wel, Mirjam G., Vițălaru, Bogdan A., Vural, Sevil A., Walkinton, Oliver, Wehrle-Martinez, Alvaro S., Widdowson, Sophie A. E., Zvarich, Irina, Chinnery, Patrick F., Falkenberg, Maria, Gustafsson, Claes M., and Murchison, Elizabeth P.

Published
2020
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12. A second transmissible cancer in Tasmanian devils

Author

Pye, Ruth J., Pemberton, David, Tovar, Cesar, Tubio, Jose M. C., Dun, Karen A., Fox, Samantha, Darby, Jocelyn, Hayes, Dane, Knowles, Graeme W., Kreiss, Alexandre, Siddle, Hannah V. T., Swift, Kate, Lyons, A. Bruce, Murchison, Elizabeth P., and Woods, Gregory M.

Published
2016

15. Transmissable Dog Cancer Genome Reveals the Origin and History of an Ancient Cell Lineage

Author

Murchison, Elizabeth P., Wedge, David C., Alexandrov, Ludmil B., Fu, Beiyuan, Martincorena, Inigo, Ning, Zemin, Tubio, Jose M. C., Werner, Emma I., Allen, Jan, De Nardi, Andrigo Barboza, Donelan, Edward M., Marino, Gabriele, Fassati, Ariberto, Campbell, Peter J., Yang, Fengtang, Burt, Austin, Weiss, Robin A., and Stratton, Michael R.

Published
2014

16. The evolution of two transmissible cancers in Tasmanian devils

Author

Stammnitz, Maximilian R., primary, Gori, Kevin, additional, Kwon, Young Mi, additional, Harry, Ed, additional, Martin, Fergal J., additional, Billis, Konstantinos, additional, Cheng, Yuanyuan, additional, Baez-Ortega, Adrian, additional, Chow, William, additional, Comte, Sebastien, additional, Eggertsson, Hannes, additional, Fox, Samantha, additional, Hamede, Rodrigo, additional, Jones, Menna E., additional, Lazenby, Billie, additional, Peck, Sarah, additional, Pye, Ruth, additional, Quail, Michael A., additional, Swift, Kate, additional, Wang, Jinhong, additional, Wood, Jonathan, additional, Howe, Kerstin, additional, Stratton, Michael R., additional, Ning, Zemin, additional, and Murchison, Elizabeth P., additional

Published
2022
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19. The Tasmanian Devil Transcriptome Reveals Schwann Cell Origins of a Clonally Transmissible Cancer

Author

Murchison, Elizabeth P., Tovar, Cesar, Hsu, Arthur, Bender, Hannah S., Kheradpour, Pouya, Rebbeck, Clare A., Obendorf, David, Conlan, Carly, Bahlo, Melanie, Blizzard, Catherine A., Pyecroft, Stephen, Kreiss, Alexandre, Kellis, Manolis, Stark, Alexander, Harkins, Timothy T., Graves, Jennifer A. Marshall, Woods, Gregory M., Hannon, Gregory J., and Papenfuss, Anthony T.

Published
2010
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23. Somatic mutation rates scale with lifespan across mammals

Author

Cagan, Alex, primary, Baez-Ortega, Adrian, additional, Brzozowska, Natalia, additional, Abascal, Federico, additional, Coorens, Tim H. H., additional, Sanders, Mathijs A., additional, Lawson, Andrew R. J., additional, Harvey, Luke M. R., additional, Bhosle, Shriram, additional, Jones, David, additional, Alcantara, Raul E., additional, Butler, Timothy M., additional, Hooks, Yvette, additional, Roberts, Kirsty, additional, Anderson, Elizabeth, additional, Lunn, Sharna, additional, Flach, Edmund, additional, Spiro, Simon, additional, Januszczak, Inez, additional, Wrigglesworth, Ethan, additional, Jenkins, Hannah, additional, Dallas, Tilly, additional, Masters, Nic, additional, Perkins, Matthew W., additional, Deaville, Robert, additional, Druce, Megan, additional, Bogeska, Ruzhica, additional, Milsom, Michael D., additional, Neumann, Björn, additional, Gorman, Frank, additional, Constantino-Casas, Fernando, additional, Peachey, Laura, additional, Bochynska, Diana, additional, John Smith, Ewan St., additional, Gerstung, Moritz, additional, Campbell, Peter J., additional, Murchison, Elizabeth P., additional, Stratton, Michael R., additional, and Martincorena, Iñigo, additional

Published
2021
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24. Pseudogene-derived small interfering RNAs regulate gene expression in mouse oocytes

Author

Tam, Oliver H., Aravin, Alexei A., Stein, Paula, Girard, Angelique, Murchison, Elizabeth P., Cheloufi, Sihem, Hodges, Emily, Anger, Martin, Sachidanandam, Ravi, Schultz, Richard M., and Hannon, Gregory J.

Subjects
Gene expression -- Physiological aspects -- Genetic aspects, Oocytes -- Genetic aspects -- Physiological aspects, RNA -- Properties -- Physiological aspects -- Genetic aspects, Environmental issues, Science and technology, Zoology and wildlife conservation, Physiological aspects, Genetic aspects, Properties
Abstract

Pseudogenes populate the mammalian genome as remnants of artefactual incorporation of coding messenger RNAs into transposon pathways (1). Here we show that a subset of pseudogenes generates endogenous small interfering [...]

Published
2008

26. Characterization of Dicer-deficient murine embryonic stem cells

Author

Murchison, Elizabeth P., Partridge, Janet F., Tam, Oliver H., Cheloufi, Sihem, and Hannon, Gregory J.

Subjects
Centromeres -- Research, Science and technology
Abstract

Dicer is an RNase Ill-family nuclease that initiates RNA interference (RNAi) and related phenomena by generation of the small RNAs that determine the specificity of these gene silencing pathways. We have previously shown that Dicer is essential for mammalian development, with Dicer-deficient mice dying at embryonic day 7.5 with a lack of detectable multipotent stem cells. To permit a more detailed investigation of the biological roles of Dicer, we have generated embryonic stem cell lines in which their single Dicer gene can be conditionally inactivated. As expected, Dicer loss compromises maturation of microRNAs and leads to a defect in gene silencing triggered by long dsRNAs. However, the absence of Dicer does not affect the ability of small interfering RNAs to repress gene expression. Of interest, Dicer loss does compromise the proliferation of ES cells, possibly rationalizing the phenotype previously observed in Dicer-null animals. Dicer loss also affects the abundance of transcripts from mammalian centromeres but does so without a pronounced affect on histone modification status at pericentric repeats or methylation of centromeric DNA. These studies provide a conditional model of RNAi deficiency in mammals that will permit the dissection of the biological roles of the RNAi machinery in cultured mammalian cells. centromeres | RNA interference

Published
2005

27. Evolution and lineage dynamics of a transmissible cancer in Tasmanian devils

Author

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

Published
2020
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28. Searching for transmissible cancers among the mussels of Europe.

Author

Baez‐Ortega, Adrian and Murchison, Elizabeth P.

Subjects
*CLONE cells, *ANIMAL cloning, *CANCER cells, *CHIMERISM, *MOLLUSKS, *CLAMS, *MYTILUS galloprovincialis, *MUSSELS
Abstract

Transmissible cancers are infectious malignant cell clones that spread among individuals through transfer of living cancer cells. Several such clones have been identified in various species of marine bivalve molluscs, including mussels, clams and cockles. These parasitic cell lineages cause a leukaemia‐like disease called disseminated neoplasia, and are presumed to pass between hosts by ingestion of water‐borne cancer cells during filter feeding. Although occasional cases of transmissible cancer had previously been identified in mussels of the genus Mytilus in Europe, the number of distinct clones affecting these animals, and their prevalence, was unknown. In this issue of Molecular Ecology, Hammel et al. (2021) present findings from a large‐scale screen for transmissible cancer across 5907 European Mytilus mussels. Using a genotyping approach, Hammel et al. searched for signal of genetic chimerism, which can arise due to infection by transmissible cancer cells. The screen detected a previously identified globally distributed mussel transmissible cancer at very low prevalence, and found no evidence of additional contagious clones. A parallel histological screen additionally revealed low prevalence of a nontransmissible form of disseminated neoplasia. By quantifying the burden of disseminated neoplasia in European mussel populations, this study provides strong foundations for future work investigating the origins, evolution and impacts of transmissible cancers in mussels. [ABSTRACT FROM AUTHOR]

Published
2022
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29. Mutational, transcriptional and viral shedding dynamics of the marine turtle fibropapillomatosis tumor epizootic

Author

Yetsko, Kelsey, primary, Farrell, Jessica, additional, Stammnitz, Maximilian R., additional, Whitmore, Liam, additional, Whilde, Jenny, additional, Eastman, Catherine B., additional, Ramia, Devon Rollinson, additional, Thomas, Rachel, additional, Krstic, Aleksandar, additional, Linser, Paul, additional, Creer, Simon, additional, Carvalho, Gary, additional, Burkhalter, Brooke, additional, Murchison, Elizabeth P., additional, Schnitzler, Christine, additional, and Duffy, David J., additional

Published
2020
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30. Expansion of CORE-SINEs in the genome of the Tasmanian devil

Author

Nilsson Maria A, Janke Axel, Murchison Elizabeth P, Ning Zemin, and Hallström Björn M

Subjects
SINE, WSINE1, Retroposon, Tasmanian devil, Sarcophilus, Genome, Marsupials, Biotechnology, TP248.13-248.65, Genetics, QH426-470
Abstract

Abstract Background The genome of the carnivorous marsupial, the Tasmanian devil (Sarcophilus harrisii, Order: Dasyuromorphia), was sequenced in the hopes of finding a cure for or gaining a better understanding of the contagious devil facial tumor disease that is threatening the species’ survival. To better understand the Tasmanian devil genome, we screened it for transposable elements and investigated the dynamics of short interspersed element (SINE) retroposons. Results The temporal history of Tasmanian devil SINEs, elucidated using a transposition in transposition analysis, indicates that WSINE1, a CORE-SINE present in around 200,000 copies, is the most recently active element. Moreover, we discovered a new subtype of WSINE1 (WSINE1b) that comprises at least 90% of all Tasmanian devil WSINE1s. The frequencies of WSINE1 subtypes differ in the genomes of two of the other Australian marsupial orders. A co-segregation analysis indicated that at least 66 subfamilies of WSINE1 evolved during the evolution of Dasyuromorphia. Using a substitution rate derived from WSINE1 insertions, the ages of the subfamilies were estimated and correlated with a newly established phylogeny of Dasyuromorphia. Phylogenetic analyses and divergence time estimates of mitochondrial genome data indicate a rapid radiation of the Tasmanian devil and the closest relative the quolls (Dasyurus) around 14 million years ago. Conclusions The radiation and abundance of CORE-SINEs in marsupial genomes indicates that they may be a major player in the evolution of marsupials. It is evident that the early phases of evolution of the carnivorous marsupial order Dasyuromorphia was characterized by a burst of SINE activity. A correlation between a speciation event and a major burst of retroposon activity is for the first time shown in a marsupial genome.

Published
2012
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31. The Origins and Vulnerabilities of Two Transmissible Cancers in Tasmanian Devils

Author

Stammnitz, Maximilian R, Coorens, Tim HH, Gori, Kevin C, Hayes, Dane, Fu, Beiyuan, Wang, Jinhong, Martin-Herranz, Daniel E, Alexandrov, Ludmil B, Baez-Ortega, Adrian, Barthorpe, Syd, Beck, Alexandra, Giordano, Francesca, Knowles, Graeme W, Kwon, Young Mi, Hall, George, Price, Stacey, Pye, Ruth J, Tubio, Jose MC, Siddle, Hannah VT, Sohal, Sukhwinder Singh, Woods, Gregory M, McDermott, Ultan, Yang, Fengtang, Garnett, Mathew J, Ning, Zemin, Murchison, Elizabeth P, Stammnitz, Maximillian [0000-0002-1704-9199], Gori, Kevin [0000-0001-7975-4275], Wang, Jinhong [0000-0001-9773-1317], Murchison, Elizabeth [0000-0001-7462-8907], and Apollo - University of Cambridge Repository

Subjects
Gene Editing, Male, cancer genomics, contagious cancer, cancer evolution, conservation, Gene Dosage, Immunity, DFTD, Chromosomes, Mammalian, Article, Clone Cells, Marsupialia, Tasmanian devils, Cell Line, Tumor, Mutation, cancer, Animals, transmissible cancer, Female, Receptors, Platelet-Derived Growth Factor, drug screening, marsupials, Facial Neoplasms
Abstract

Summary Transmissible cancers are clonal lineages that spread through populations via contagious cancer cells. Although rare in nature, two facial tumor clones affect Tasmanian devils. Here we perform comparative genetic and functional characterization of these lineages. The two cancers have similar patterns of mutation and show no evidence of exposure to exogenous mutagens or viruses. Genes encoding PDGF receptors have copy number gains and are present on extrachromosomal double minutes. Drug screening indicates causative roles for receptor tyrosine kinases and sensitivity to inhibitors of DNA repair. Y chromosome loss from a male clone infecting a female host suggests immunoediting. These results imply that Tasmanian devils may have inherent susceptibility to transmissible cancers and present a suite of therapeutic compounds for use in conservation., Graphical Abstract, Highlights • Tasmanian devil transmissible cancers arose from similar tissues in two individuals • Similar mutation patterns and driver candidates imply common oncogenic processes • Losses at B2M and Y chromosome loci suggest selection to escape immune detection • Receptor tyrosine kinases and DNA repair factors implicated as therapeutic targets, Stammnitz et al. show that the two transmissible cancer clones that affect Tasmanian devils are very similar in their tissues-of-origin, mutational patterns and driver gene candidates. Importantly, these cancers are both highly sensitive to inhibitors of some receptor tyrosine kinases as well as to inhibitors of DNA repair.

Published
2018

32. Two of a kind: transmissible Schwann cell cancers in the endangered Tasmanian devil (Sarcophilus harrisii)

Author

Patchett, Amanda L., primary, Coorens, Tim H. H., additional, Darby, Jocelyn, additional, Wilson, Richard, additional, McKay, Matthew J., additional, Kamath, Karthik S., additional, Rubin, Alan, additional, Wakefield, Matthew, additional, Mcintosh, Lachlan, additional, Mangiola, Stefano, additional, Pye, Ruth J., additional, Flies, Andrew S., additional, Corcoran, Lynn M., additional, Lyons, A. Bruce, additional, Woods, Gregory M., additional, Murchison, Elizabeth P., additional, Papenfuss, Anthony T., additional, and Tovar, Cesar, additional

Published
2019
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33. Somatic evolution and global expansion of an ancient transmissible cancer lineage

Author

Baez-Ortega, Adrian, primary, Gori, Kevin, additional, Strakova, Andrea, additional, Allen, Janice L., additional, Allum, Karen M., additional, Bansse-Issa, Leontine, additional, Bhutia, Thinlay N., additional, Bisson, Jocelyn L., additional, Briceño, Cristóbal, additional, Castillo Domracheva, Artemio, additional, Corrigan, Anne M., additional, Cran, Hugh R., additional, Crawford, Jane T., additional, Davis, Eric, additional, de Castro, Karina F., additional, B. de Nardi, Andrigo, additional, de Vos, Anna P., additional, Delgadillo Keenan, Laura, additional, Donelan, Edward M., additional, Espinoza Huerta, Adela R., additional, Faramade, Ibikunle A., additional, Fazil, Mohammed, additional, Fotopoulou, Eleni, additional, Fruean, Skye N., additional, Gallardo-Arrieta, Fanny, additional, Glebova, Olga, additional, Gouletsou, Pagona G., additional, Häfelin Manrique, Rodrigo F., additional, Henriques, Joaquim J. G. P., additional, Horta, Rodrigo S., additional, Ignatenko, Natalia, additional, Kane, Yaghouba, additional, King, Cathy, additional, Koenig, Debbie, additional, Krupa, Ada, additional, Kruzeniski, Steven J., additional, Kwon, Young-Mi, additional, Lanza-Perea, Marta, additional, Lazyan, Mihran, additional, Lopez Quintana, Adriana M., additional, Losfelt, Thibault, additional, Marino, Gabriele, additional, Martínez Castañeda, Simón, additional, Martínez-López, Mayra F., additional, Meyer, Michael, additional, Migneco, Edward J., additional, Nakanwagi, Berna, additional, Neal, Karter B., additional, Neunzig, Winifred, additional, Ní Leathlobhair, Máire, additional, Nixon, Sally J., additional, Ortega-Pacheco, Antonio, additional, Pedraza-Ordoñez, Francisco, additional, Peleteiro, Maria C., additional, Polak, Katherine, additional, Pye, Ruth J., additional, Reece, John F., additional, Rojas Gutierrez, Jose, additional, Sadia, Haleema, additional, Schmeling, Sheila K., additional, Shamanova, Olga, additional, Sherlock, Alan G., additional, Stammnitz, Maximilian, additional, Steenland-Smit, Audrey E., additional, Svitich, Alla, additional, Tapia Martínez, Lester J., additional, Thoya Ngoka, Ismail, additional, Torres, Cristian G., additional, Tudor, Elizabeth M., additional, van der Wel, Mirjam G., additional, Viţălaru, Bogdan A., additional, Vural, Sevil A., additional, Walkinton, Oliver, additional, Wang, Jinhong, additional, Wehrle-Martinez, Alvaro S., additional, Widdowson, Sophie A. E., additional, Stratton, Michael R., additional, Alexandrov, Ludmil B., additional, Martincorena, Iñigo, additional, and Murchison, Elizabeth P., additional

Published
2019
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34. Tracing the rise of malignant cell lines: Distribution, epidemiology and evolutionary interactions of two transmissible cancers in Tasmanian devils

Author

James, Samantha, primary, Jennings, Geordie, additional, Kwon, Young Mi, additional, Stammnitz, Maximilian, additional, Fraik, Alexandra, additional, Storfer, Andrew, additional, Comte, Sebastien, additional, Pemberton, David, additional, Fox, Samantha, additional, Brown, Bill, additional, Pye, Ruth, additional, Woods, Gregory, additional, Lyons, Bruce, additional, Hohenlohe, Paul A., additional, McCallum, Hamish, additional, Siddle, Hannah, additional, Thomas, Frédéric, additional, Ujvari, Beata, additional, Murchison, Elizabeth P., additional, Jones, Menna, additional, and Hamede, Rodrigo, additional

Published
2019
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35. The ERBB-STAT3 Axis Drives Tasmanian Devil Facial Tumor Disease

Author

Kosack, Lindsay, primary, Wingelhofer, Bettina, additional, Popa, Alexandra, additional, Orlova, Anna, additional, Agerer, Benedikt, additional, Vilagos, Bojan, additional, Majek, Peter, additional, Parapatics, Katja, additional, Lercher, Alexander, additional, Ringler, Anna, additional, Klughammer, Johanna, additional, Smyth, Mark, additional, Khamina, Kseniya, additional, Baazim, Hatoon, additional, de Araujo, Elvin D., additional, Rosa, David A., additional, Park, Jisung, additional, Tin, Gary, additional, Ahmar, Siawash, additional, Gunning, Patrick T., additional, Bock, Christoph, additional, Siddle, Hannah V., additional, Woods, Gregory M., additional, Kubicek, Stefan, additional, Murchison, Elizabeth P., additional, Bennett, Keiryn L., additional, Moriggl, Richard, additional, and Bergthaler, Andreas, additional

Published
2019
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36. Tasman-PCR: a genetic diagnostic assay for Tasmanian devil facial tumour diseases

Author

Kwon, Young Mi, primary, Stammnitz, Maximilian R., additional, Wang, Jinhong, additional, Swift, Kate, additional, Knowles, Graeme W., additional, Pye, Ruth J., additional, Kreiss, Alexandre, additional, Peck, Sarah, additional, Fox, Samantha, additional, Pemberton, David, additional, Jones, Menna E., additional, Hamede, Rodrigo, additional, and Murchison, Elizabeth P., additional

Published
2018
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38. The newly-arisen Devil facial tumour disease 2 (DFT2) reveals a mechanism for the emergence of a contagious cancer

Author

Caldwell, Alison, primary, Coleby, Rachel, additional, Tovar, Cesar, additional, Stammnitz, Maximilian R, additional, Kwon, Young Mi, additional, Owen, Rachel S, additional, Tringides, Marios, additional, Murchison, Elizabeth P, additional, Skjødt, Karsten, additional, Thomas, Gareth J, additional, Kaufman, Jim, additional, Elliott, Tim, additional, Woods, Gregory M, additional, and Siddle, Hannah VT, additional

Published
2018
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39. The evolutionary history of dogs in the Americas

Author

Ní Leathlobhair, Máire, primary, Perri, Angela R., additional, Irving-Pease, Evan K., additional, Witt, Kelsey E., additional, Linderholm, Anna, additional, Haile, James, additional, Lebrasseur, Ophelie, additional, Ameen, Carly, additional, Blick, Jeffrey, additional, Boyko, Adam R., additional, Brace, Selina, additional, Cortes, Yahaira Nunes, additional, Crockford, Susan J., additional, Devault, Alison, additional, Dimopoulos, Evangelos A., additional, Eldridge, Morley, additional, Enk, Jacob, additional, Gopalakrishnan, Shyam, additional, Gori, Kevin, additional, Grimes, Vaughan, additional, Guiry, Eric, additional, Hansen, Anders J., additional, Hulme-Beaman, Ardern, additional, Johnson, John, additional, Kitchen, Andrew, additional, Kasparov, Aleksei K., additional, Kwon, Young-Mi, additional, Nikolskiy, Pavel A., additional, Lope, Carlos Peraza, additional, Manin, Aurélie, additional, Martin, Terrance, additional, Meyer, Michael, additional, Myers, Kelsey Noack, additional, Omura, Mark, additional, Rouillard, Jean-Marie, additional, Pavlova, Elena Y., additional, Sciulli, Paul, additional, Sinding, Mikkel-Holger S., additional, Strakova, Andrea, additional, Ivanova, Varvara V., additional, Widga, Christopher, additional, Willerslev, Eske, additional, Pitulko, Vladimir V., additional, Barnes, Ian, additional, Gilbert, M. Thomas P., additional, Dobney, Keith M., additional, Malhi, Ripan S., additional, Murchison, Elizabeth P., additional, Larson, Greger, additional, and Frantz, Laurent A. F., additional

Published
2018
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40. Author response: The newly-arisen Devil facial tumour disease 2 (DFT2) reveals a mechanism for the emergence of a contagious cancer

Author

Caldwell, Alison, primary, Coleby, Rachel, additional, Tovar, Cesar, additional, Stammnitz, Maximilian R, additional, Kwon, Young Mi, additional, Owen, Rachel S, additional, Tringides, Marios, additional, Murchison, Elizabeth P, additional, Skjødt, Karsten, additional, Thomas, Gareth J, additional, Kaufman, Jim, additional, Elliott, Tim, additional, Woods, Gregory M, additional, and Siddle, Hannah VT, additional

Published
2018
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41. The ERBB-STAT3 Axis Drives Tasmanian Devil Facial Tumor Disease

Author

Kosack, Lindsay, primary, Wingelhofer, Bettina, additional, Popa, Alexandra, additional, Vilagos, Bojan, additional, Orlova, Anna, additional, Majek, Peter, additional, Parapatics, Katja, additional, Lercher, Alexander, additional, Agerer, Benedikt, additional, Ringler, Anna, additional, Klughammer, Johanna, additional, Smyth, Mark, additional, Khamina, Kseniya, additional, Baazim, Hatoon, additional, Rosa, David A., additional, Park, Jisung, additional, Gunning, Patrick T., additional, Bock, Christoph, additional, Siddle, Hannah V., additional, Kubicek, Stefan, additional, Murchison, Elizabeth P., additional, Bennett, Keiryn L., additional, Moriggl, Richard, additional, and Bergthaler, Andreas, additional

Published
2018
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42. The Origins and Vulnerabilities of Two Transmissible Cancers in Tasmanian Devils

Author

Stammnitz, Maximilian R., primary, Coorens, Tim H.H., additional, Gori, Kevin C., additional, Hayes, Dane, additional, Fu, Beiyuan, additional, Wang, Jinhong, additional, Martin-Herranz, Daniel E., additional, Alexandrov, Ludmil B., additional, Baez-Ortega, Adrian, additional, Barthorpe, Syd, additional, Beck, Alexandra, additional, Giordano, Francesca, additional, Knowles, Graeme W., additional, Kwon, Young Mi, additional, Hall, George, additional, Price, Stacey, additional, Pye, Ruth J., additional, Tubio, Jose M.C., additional, Siddle, Hannah V.T., additional, Sohal, Sukhwinder Singh, additional, Woods, Gregory M., additional, McDermott, Ultan, additional, Yang, Fengtang, additional, Garnett, Mathew J., additional, Ning, Zemin, additional, and Murchison, Elizabeth P., additional

Published
2018
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44. Critical roles for Dicer in the female germline

Author

Murchison, Elizabeth P., Schultz, Richard M., Stein, Paula, Hannon, Gregory J., Zhenyu Xuan, Hua Pan, and Zhang, Michael Q.

Subjects
Oocytes -- Research, Infertility, Female -- Research, Biological sciences
Abstract

Dicer, an essential component of the ribonucleic acid interference (RNAi) pathways, is necessary to control mouse oocyte gene regulation and genome organization. An examination of tissue-restricted Dicer loss in mice indicates a critical role for Dicer during meiosis in the female germline, essential for turnover of a substantial subset of maternal transcripts normally lost during oocyte maturation.

Published
2007

46. Enhancer evolution across 20 mammalian species

Author

Villar, Diego, Berthelot, Camille, Aldridge, Sarah, Rayner, Tim F, Lukk, Margus, Pignatelli, Miguel, Park, Thomas J, Deaville, Robert, Erichsen, Jonathan T, Jasinska, Anna J, Turner, James MA, Bertelsen, Mads F, Murchison, Elizabeth P, Flicek, Paul, Odom, Duncan T, Murchison, Elizabeth [0000-0001-7462-8907], Odom, Duncan [0000-0001-6201-5599], and Apollo - University of Cambridge Repository

Subjects
Evolution, Molecular, Histone Code, Mammals, Enhancer Elements, Genetic, Liver, Biochemistry, Genetics and Molecular Biology(all), Animals, Humans, RE, Promoter Regions, Genetic, Transcription Factors
Abstract

SummaryThe mammalian radiation has corresponded with rapid changes in noncoding regions of the genome, but we lack a comprehensive understanding of regulatory evolution in mammals. Here, we track the evolution of promoters and enhancers active in liver across 20 mammalian species from six diverse orders by profiling genomic enrichment of H3K27 acetylation and H3K4 trimethylation. We report that rapid evolution of enhancers is a universal feature of mammalian genomes. Most of the recently evolved enhancers arise from ancestral DNA exaptation, rather than lineage-specific expansions of repeat elements. In contrast, almost all liver promoters are partially or fully conserved across these species. Our data further reveal that recently evolved enhancers can be associated with genes under positive selection, demonstrating the power of this approach for annotating regulatory adaptations in genomic sequences. These results provide important insight into the functional genetics underpinning mammalian regulatory evolution.

Published
2015

47. Conservation of small RNA pathways in platypus

Author

Murchison, Elizabeth P., Kheradpour, Pouya, Sachidanandam, Ravi, Smith, Carly, Hodges, Emily, Zhenyu Xuan, Kellis, Manolis, Grutzner, Frank, Stark, Alexander, and Hannon, Gregory J.

Subjects
RNA -- Research, Platypus -- Genetic aspects, Nucleotide sequence -- Analysis, Health
Abstract

The investigation of the small RNA pathways of monotremes by deep sequencing of six platypus and echidna tissues is described. It is observed that the highly conserved microRNA species exhibit their signature tissue-specific expression patterns and also large quickly evolving cluster of microRNAs on platypus chromosomes XI, which is distinct to monotremes are seen.

Published
2008

50. Mitochondrial genetic diversity, selection and recombination in a canine transmissible cancer

Author

Strakova, Andrea, primary, Ní Leathlobhair, Máire, additional, Wang, Guo-Dong, additional, Yin, Ting-Ting, additional, Airikkala-Otter, Ilona, additional, Allen, Janice L, additional, Allum, Karen M, additional, Bansse-Issa, Leontine, additional, Bisson, Jocelyn L, additional, Castillo Domracheva, Artemio, additional, de Castro, Karina F, additional, Corrigan, Anne M, additional, Cran, Hugh R, additional, Crawford, Jane T, additional, Cutter, Stephen M, additional, Delgadillo Keenan, Laura, additional, Donelan, Edward M, additional, Faramade, Ibikunle A, additional, Flores Reynoso, Erika, additional, Fotopoulou, Eleni, additional, Fruean, Skye N, additional, Gallardo-Arrieta, Fanny, additional, Glebova, Olga, additional, Häfelin Manrique, Rodrigo F, additional, Henriques, Joaquim JGP, additional, Ignatenko, Natalia, additional, Koenig, Debbie, additional, Lanza-Perea, Marta, additional, Lobetti, Remo, additional, Lopez Quintana, Adriana M, additional, Losfelt, Thibault, additional, Marino, Gabriele, additional, Martincorena, Inigo, additional, Martínez Castañeda, Simón, additional, Martínez-López, Mayra F, additional, Meyer, Michael, additional, Nakanwagi, Berna, additional, De Nardi, Andrigo B, additional, Neunzig, Winifred, additional, Nixon, Sally J, additional, Onsare, Marsden M, additional, Ortega-Pacheco, Antonio, additional, Peleteiro, Maria C, additional, Pye, Ruth J, additional, Reece, John F, additional, Rojas Gutierrez, Jose, additional, Sadia, Haleema, additional, Schmeling, Sheila K, additional, Shamanova, Olga, additional, Ssuna, Richard K, additional, Steenland-Smit, Audrey E, additional, Svitich, Alla, additional, Thoya Ngoka, Ismail, additional, Vițălaru, Bogdan A, additional, de Vos, Anna P, additional, de Vos, Johan P, additional, Walkinton, Oliver, additional, Wedge, David C, additional, Wehrle-Martinez, Alvaro S, additional, van der Wel, Mirjam G, additional, Widdowson, Sophie AE, additional, and Murchison, Elizabeth P, additional

Published
2016
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