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Widespread transmission of independent cancer lineages within multiple bivalve species


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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Figure 1: Analysis of tissue and haemocyte genotypes of normal mussels (M. trossulus) and mussels with disseminated neoplasia using mitochondrial and nuclear DNA markers.
Figure 2: Analysis of lineages of transmissible neoplasia in cockles (C. edule).
Figure 3: Phylogenetic analysis of neoplastic cells in P. aureus and quantification of V. corrugata cell engraftment in normal and diseased animals.

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


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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

Authors and Affiliations



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.

Additional information

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.

Extended data figures and tables

Extended Data Figure 1 Analysis of mtCOI amplified from tissue and haemocyte DNA of normal and diseased mussels (M. trossulus).

A partial region of the mtCOI gene was amplified from genomic DNA of solid tissue and haemocytes from mussels (M. trossulus) and directly sequenced (Fig. 1b). Trace images show a region flanking a representative SNP marked with an open triangle (tissue) or closed triangle (haemocytes). a, b, In normal mussels, tissue and haemocyte alleles match (with G496 at all positions). ce, In mussels with disseminated neoplasia, the tissue and haemocyte alleles are different. Neoplastic haemocytes have A at position 496 and G in tissue, with some A observable in tissue, probably because of infiltration of neoplastic haemocytes.

Extended Data Figure 2 Quantification of Steamer-like element genomic copy number in mussels (M. trossulus), cockles (C. edule), and golden carpet shell clams (P. aureus).

ad, Fragments from the SLE reverse transcriptase region and EF1α genes were cloned from each species. Haploid copy numbers of Steamer-like elements (SLE) were quantified by determining the ratio of SLE/EF1a in genomic DNA from haemocytes. Single species-specifc SLEs were analysed in (a) mussels (M. trossulus) and (b) cockles (C. edule). c, d, In golden carpet shell clams, one SLE (SLE-Pa) was cloned from a normal P. aureus (clam N2) and a different one (SLE-Vc) was cloned from neoplastic cells (clam H2). Both SLEs could be found in both species, and qPCR analysis confirmed that SLE-Pa is more highly amplified in P. aureus and has fewer copies in V. corrugata and in the neoplastic cells derived from V. corrugata.

Extended Data Table 1 Morphometric analysis of type A and type B cockle (C. edule) neoplasia
Extended Data Table 2 Primers used in PCR and qPCR

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Metzger, M., Villalba, A., Carballal, M. et al. Widespread transmission of independent cancer lineages within multiple bivalve species. Nature 534, 705–709 (2016).

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