Mitochondrial genome sequencing of marine leukaemias reveals cancer contagion between clam species in the Seas of Southern Europe

Abstract

Clonally transmissible cancers are tumour lineages that are transmitted between individuals via the transfer of living cancer cells. In marine bivalves, leukaemia-like transmissible cancers, called hemic neoplasia (HN), have demonstrated the ability to infect individuals from different species. We performed whole-genome sequencing in eight warty venus clams that were diagnosed with HN, from two sampling points located more than 1000 nautical miles away in the Atlantic Ocean and the Mediterranean Sea Coasts of Spain. Mitochondrial genome sequencing analysis from neoplastic animals revealed the coexistence of haplotypes from two different clam species. Phylogenies estimated from mitochondrial and nuclear markers confirmed this leukaemia originated in striped venus clams and later transmitted to clams of the species warty venus, in which it survives as a contagious cancer. The analysis of mitochondrial and nuclear gene sequences supports all studied tumours belong to a single neoplastic lineage that spreads in the Seas of Southern Europe.

Survival and Detection of Bivalve Transmissible Neoplasia from the Soft-Shell Clam Mya arenaria (MarBTN) in Seawater

“…DN was first confirmed to be a transmissible cancer in soft-shell clams ( Mya arenaria ) [ 5 ], and later, multiple independent lineages of transmissible cancer were identified in bivalve species worldwide [ 12 ]. To date, seven lineages of the bivalve transmissible neoplasia (BTN) in eight bivalve species have been reported [ 5 , 12 , 13 , 14 , 15 , 16 , 17 ], showing that the majority of DN cases in bivalves are likely to be a transmissible cancer, although a few cases of primary DN have been reported [ 12 , 14 , 15 ]. Given the rapid discovery of BTN lineages (seven lineages identified since 2015) and the fact that more than 20 bivalve species are known to be affected by DN [ 6 , 7 ], many more BTN lineages are likely to be found.…”

“…In many cases, the BTN that circulates in each species has arisen from a member of that same species. However, increasing cases of cross-species transmission have been reported (one lineage from Venerupis corrugata to Polititapes aureus in Galicia [ 12 ], one from Chamelea gallina to Venus verrucosa in Europe [ 17 ], and a single lineage from Mytilus trossulus now found in four Mytilus species worldwide [ 14 , 15 , 16 ]). Furthermore, in some cases, multiple independently derived lineages of BTN have been identified within the same species (as in Cerastoderma edule and Mytilus trossulus ).…”

“…CTVT and DFTD are well known to be transmitted by close physical contact, during sex and biting, respectively [ 1 , 3 , 23 , 24 , 25 ], but most adult bivalves are sessile or with limited mobility, without direct contact of soft body tissues, making widespread BTN transmission through direct contact unlikely. Since genomic evidence clearly shows that BTN cells are transmissible [ 5 , 12 , 13 , 14 , 15 , 16 , 17 ], they must be able to transmit through a different mechanism than direct physical contact. The most likely route of transmission is the release of the BTN cells into the seawater and uptake of the released cells by naïve animals through filter feeding [ 5 ].…”

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

“…BTN is a transmissible form of DN, and BTN lineages have been found in eight 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 (Metzger et al, 2016); Venus verrucosa from Europe (Garcia‐Souto et al, 2022), and four species of Mytilus mussels from around the world, M . trossulus , M .…”

“…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 & Swift, 2006;Pye et al;, and bivalve transmissible neoplasia (BTN). BTN is a transmissible form of DN, and BTN lineages have been found in eight 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 ; Venus verrucosa from Europe (Garcia-Souto et al, 2022), and four species of Mytilus mussels from around the world, M. trossulus, M. edulis, M. chilensis and M. galloprovincialis (Hammel et al, 2022;Skazina et al, 2021;Yonemitsu et al, 2019).…”