Letter | Published:

Widespread transmission of independent cancer lineages within multiple bivalve species

Nature volume 534, pages 705709 (30 June 2016) | Download Citation

Abstract

Most cancers arise from oncogenic changes in the genomes of somatic cells, and while the cells may migrate by metastasis, they remain within that single individual. Natural transmission of cancer cells from one individual to another has been observed in two distinct cases in mammals (Tasmanian devils1 and dogs2,3), but these are generally considered to be rare exceptions in nature. The discovery of transmissible cancer in soft-shell clams (Mya arenaria)4 suggested that this phenomenon might be more widespread. Here we analyse disseminated neoplasia in mussels (Mytilus trossulus), cockles (Cerastoderma edule), and golden carpet shell clams (Polititapes aureus) and find that neoplasias in all three species are attributable to independent transmissible cancer lineages. In mussels and cockles, the cancer lineages are derived from their respective host species; however, unexpectedly, cancer cells in P. aureus are all derived from Venerupis corrugata, a different species living in the same geographical area. No cases of disseminated neoplasia have thus far been found in V. corrugata from the same region. These findings show that transmission of cancer cells in the marine environment is common in multiple species, that it has originated many times, and that while most transmissible cancers are found spreading within the species of origin, cross-species transmission of cancer cells can occur.

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Accessions

Primary accessions

GenBank/EMBL/DDBJ

Data deposits

Sequences generated in this work have been deposited in GenBank under accession numbers KX018521KX018605.

References

  1. 1.

    & Allograft theory: transmission of devil facial-tumour disease. Nature 439, 549 (2006)

  2. 2.

    , , , & Clonal origin and evolution of a transmissible cancer. Cell 126, 477–487 (2006)

  3. 3.

    , , , & Origins and evolution of a transmissible cancer. Evolution 63, 2340–2349 (2009)

  4. 4.

    , , & Horizontal transmission of clonal cancer cells causes leukemia in soft-shell clams. Cell 161, 255–263 (2015)

  5. 5.

    Neoplastic diseases of commercially important marine bivalves. Aquat. Living Resour. 17, 449–466 (2004)

  6. 6.

    , , & Neoplastic diseases of marine bivalves. J. Invertebr. Pathol. 131, 83–106 (2015)

  7. 7.

    , , & Alternate pathogenesis of systemic neoplasia in the bivalve mollusc Mytilus. J. Invertebr. Pathol. 58, 231–243 (1991)

  8. 8.

    & Using flow cytometry to detect haemic neoplasia in mussels (Mytilus trossulus) from the Pacific Coast of Southern British Columbia, Canada. J. Invertebr. Pathol. 117, 68–72 (2014)

  9. 9.

    , , & Variations in p53-like cDNA sequence are correlated with mussel haemic neoplasia: a potential molecular-level tool for biomonitoring. Mutat. Res. 701, 145–152 (2010)

  10. 10.

    , & Disseminated neoplasia and large foci indicating heavy haemocytic infiltration in cockles Cerastoderma edule from Galicia (NW Spain). Dis. Aquat. Organ. 46, 213–216 (2001)

  11. 11.

    , , & Long-term epidemiological study of disseminated neoplasia of cockles in Galicia (NW Spain): temporal patterns at individual and population levels, influence of environmental and cockle-based factors and lethality. J. Fish Dis. (2016)

  12. 12.

    , , & Disseminated neoplasia in clams Venerupis aurea from Galicia (NW Spain): histopathology, ultrastructure and ploidy of the neoplastic cells, and comparison of diagnostic procedures. J. Invertebr. Pathol. 112, 16–19 (2013)

  13. 13.

    , , , & Parasites and pathologic conditions of the cockle Cerastoderma edule populations of the coast of Galicia (NW Spain). J. Invertebr. Pathol. 78, 87–97 (2001)

  14. 14.

    Estudio Patológico de las Poblaciones de Berberecho Cerastoderma edule (L.) de Galicia. Ph.D. thesis, Univ. Santiago do Compostela (2006)

  15. 15.

    , , , & Development of twelve polymorphic microsatellite markers in the edible cockle Cerastoderma edule (Bivalvia: Cardiidae). Conserv. Genet. Resour. 1, 107–109 (2009)

  16. 16.

    , & Poppr: an R package for genetic analysis of populations with clonal, partially clonal, and/or sexual reproduction. PeerJ 2, e281 (2014)

  17. 17.

    & Inheritance of microsatellite loci in the white sturgeon (Acipenser transmontanus). Genome 45, 1064–1076 (2002)

  18. 18.

    et al. Activation of transcription and retrotransposition of a novel retroelement, Steamer, in neoplastic hemocytes of the mollusk Mya arenaria. Proc. Natl Acad. Sci. USA 111, 14175–14180 (2014)

  19. 19.

    et al. A second transmissible cancer in Tasmanian devils. Proc. Natl Acad. Sci. USA 113, 374–379 (2016)

  20. 20.

    & Transmission of transmissible venereal tumor of the dog to the coyote. Am. J. Vet. Res. 40, 409–410 (1979)

  21. 21.

    Recherches Experimentales sur le Sarcome de Sticker. Docteur ès Sciences Naturalles thesis, Univ. Paris (1965)

  22. 22.

    Transplantables Rundzellensarkom des Hundes. Z. Krebsforsch. 4, 227–314 (1906)

  23. 23.

    An experimental investigation of infective sarcoma of the dog, with a consideration of its relationship to cancer. J. Pathol. Bacteriol. 12, 384–425 (1908)

  24. 24.

    Biologie des Rundzellensarkoms des Hundes. Munch. med. Wochenschr. No. 5, 238–239 (1912)

  25. 25.

    & The changing global distribution and prevalence of canine transmissible venereal tumour. BMC Vet. Res. 10, 168 (2014)

  26. 26.

    , & Field and laboratory transmission studies of haemic neoplasia in the soft-shell clam, Mya arenaria, from Atlantic Canada. J. Fish Dis. (2015)

  27. 27.

    , , & Failure of transmission of hemic neoplasia of bay mussels, Mytilus trossulus, to other bivalve species. J. Invertebr. Pathol. 57, 435–436 (1991)

  28. 28.

    , , & Molecular data from the 16S rRNA gene for the phylogeny of Veneridae (Mollusca: Bivalvia). Mar. Biol. 142, 1125–1130 (2003)

  29. 29.

    et al. Malignant transformation of Hymenolepis nana in a human host. N. Engl. J. Med. 373, 1845–1852 (2015)

  30. 30.

    , & Invertebrate p53-like mRNA isoforms are differentially expressed in mussel haemic neoplasia. Mar. Environ. Res. 66, 412–421 (2008)

  31. 31.

    , , & NOAA Technical Memorandum NOS NCCOS Vol. 5 (NOAA/National Centers for Coastal Ocean Science, 2004)

  32. 32.

    , , & Expression of mutant protein p53 and Hsp70 and Hsp90 chaperones in cockles Cerastoderma edule affected by neoplasia. Dis. Aquat. Organ. 90, 215–222 (2010)

  33. 33.

    , , , & DNA primers for amplification of mitochondrial cytochrome c oxidase subunit I from diverse metazoan invertebrates. Mol. Mar. Biol. Biotechnol. 3, 294–299 (1994)

  34. 34.

    & Contrasting morphological and molecular variation in Coralliophila meyendorffii (Muricidae, Coralliophilinae). J. Molluscan Stud. 67, 243–245 (2001)

  35. 35.

    & Molecular phylogenetics in 2D: ITS2 rRNA evolution and sequence-structure barcode from Veneridae to Bivalvia. Mol. Phylogenet. Evol. 65, 792–798 (2012)

  36. 36.

    et al. New algorithms and methods to estimate maximum-likelihood phylogenies: assessing the performance of PhyML 3.0. Syst. Biol. 59, 307–321 (2010)

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Acknowledgements

M.J.M. and S.P.G. were supported by the Howard Hughes Medical Institute and Training Grant T32 CA009503. D.I., M.J.C., and A.V. were supported by the Consellería do Mar da Xunta de Galicia, through the project PGIDIT-CIMA 13/03. We thank J. Ausió for help in collection of M. trossulus from Vancouver Island.

Author information

Affiliations

  1. Department of Biochemistry and Molecular Biophysics, Columbia University, New York 10032, USA

    • Michael J. Metzger
    •  & Stephen P. Goff
  2. Howard Hughes Medical Institute, New York, New York 10032, USA

    • Michael J. Metzger
    •  & Stephen P. Goff
  3. Centro de Investigacións Mariñas, Consellería do Mar, Xunta de Galicia, Vilanova de Arousa 36620, Spain

    • Antonio Villalba
    • , María J. Carballal
    •  & David Iglesias
  4. Department of Life Sciences, University of Alcalá, Alcalá de Henares 28871, Spain

    • Antonio Villalba
  5. Environment Canada, Water Science & Technology Directorate, Burlington, Ontario L7R 4A6, Canada

    • James Sherry
    •  & Carol Reinisch
  6. Chemical and Biological Engineering, University of British Columbia, Vancouver V6T 1Z3, Canada

    • Annette F. Muttray
    •  & Susan A. Baldwin
  7. SLR Consulting Canada Ltd., Vancouver V6J 1V4, Canada

    • Annette F. Muttray
  8. Department of Microbiology and Immunology, Columbia University, New York, New York 10032, USA

    • Stephen P. Goff

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Contributions

M.J.M. and S.P.G. wrote the manuscript. M.J.M. conducted molecular analyses. A.F.M. and S.A.B. collected and diagnosed M. trossulus from West Vancouver. J.S. and C.R. collected and diagnosed M. trossulus from Vancouver Island. D.I., M.J.C., and A.V. collected and diagnosed C. edule and P. aureus. M.J.C. produced micrographs of C. edule neoplastic haemocytes, and D.I. conducted morphometric analysis.

Corresponding author

Correspondence to Stephen P. Goff.

Reviewer Information Nature thanks E. Murchison, S. O’Brien, G. De Vico, R. A. Weiss and the other anonymous reviewer(s) for their contribution to the peer review of this work.

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DOI

https://doi.org/10.1038/nature18599

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