Prevalence and polymorphism of a mussel transmissible cancer in Europe

Abstract

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.

Horizontal transmission of disseminated neoplasia in the widespread clam Limecola balthica from the Southern Baltic Sea

“…To date there are three recognized types of cancer with transmissible aetiology: canine transmissible venereal tumour (CTVT) (Murgia et al 2006, Rebbeck et al 2009, devil facial tumour disease (DFTD) (Pearse et al 2006), and bivalve transmissible neoplasia (BTN). BTN is a transmissible form of DN, and BTN lineages have been found in seven bivalve species: soft-shell clam M. arenaria from Atlantic coast of North America (Metzger et al 2015); Cerastoderma edule and Polititapes aureus from Galician coast of Spain ; and four species of Mytilus mussels from around the world, M. trossulus , M. edulis , M. chilensis and M. galloprovincialis (Yonemitsu et al 2019, Skazina et al 2021, Hammel et al 2021. DN transmission in the above-mentioned bivalve species was confirmed using polymorphic microsatellite alleles of nuclear DNA and sequence analysis of mitochondrial and nuclear genes.…”

Genotype data not consistent with clonal transmission of sea turtle fibropapillomatosis or goldfish schwannoma

“…While we did not find evidence of transmissible cancer, the genotyping and experimental transmission studies described here are limited to a small set of samples and cannot exclude the existence of different tumour subtypes in these species, some of which may be transmissible. Indeed, the co-occurrence of transmissible and non-transmissible forms of bivalve haemic neoplasia in mussels confirms that larger-scale sampling and genetic identification may be required in order to definitively rule out direct cancer cell transmission 17 , 67 . Furthermore, although care was taken to biopsy neoplastic sites in both cancers, it is worth noting that we were unable to confirm the proportion of neoplastic cells in the samples analysed in this study.…”

“…These clones can ‘metastasize’ within populations, having adapted to transmit across external environments and evade host immune responses. Ten naturally occurring transmissible cancer lineages have been described: one in domestic dogs 9 – 11 , two lineages in Tasmanian devils 12 , 13 as well as multiple independent lineages in marine bivalves 14 – 17 . In this study, we assessed the hypothesis of clonal transmission in two animal cancers.…”

Survival and detection of bivalve transmissible neoplasia from the soft-shell clam Mya arenaria (MarBTN) in seawater

“…A very recent study of the MtrBTN2 lineage of transmissible cancer, known to infect four Mytilus species around the world (14)(15)(16), has shown that these cancer cells also can survive for a few days in seawater (26). The authors assayed cell survival at 18°C; our results showing longer survival of MarBTN at lower temperatures suggest that their finding of 6-day survival may be an underestimate.…”

“…To date, seven lineages of the bivalve transmissible neoplasia (BTN) in eight bivalve species have been reported (5,(12)(13)(14)(15)(16)(17). In many cases, the BTN that circulates in each species has arisen from a member of that same species.…”