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.

Highlights

  • Cancers are clonal cell lineages that arise due to somatic changes that promote cell proliferation and survival (Stratton et al, 2009)

  • We investigated the prevalence of Hemic neoplasia (HN) in the warty venus clam (V. verrucosa), a saltwater bivalve found in the Atlantic Coast of Europe and the Mediterranean Sea

  • Three HN-p­ ositive specimens (ERVV17-2­ 995, ERVV17-­2997, and ERVV17-3­ 193) were collected in Galicia, northwest of the Iberian Peninsula in the Atlantic Ocean, and another five specimens (EMVV18-3­ 73, EMVV18-3­ 76, EMVV18-3­ 91, EMVV18-3­ 95, and EMVV18-­400) were collected in the Balearic Islands, bathed by the Mediterranean Sea (Figure 1a; Supplementary file 1). Four of these specimens (ERVV17-­2995, ERVV17-3­ 193, EMVV18-3­ 91, and EMVV18-­395) showed a severe form of the disease – classified as N3 stage – which is characterized by high levels of neoplastic cells infiltrating the gills, different levels of infiltration of the digestive gland and gonad, and low/very low infiltration of the mantle and foot (Figure 1d,e; Figure 1—figure supplement 1); one specimen (EMVV18-­400) was found that was affected with an intermediate form of the disease – N2 stage – characterized by low levels of neoplastic cells infiltrating the gill vessels, eLife digest In humans and other animals, cancer cells divide excessively, forming tumours or flooding the blood, but they rarely spread to other individuals

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Summary

Introduction

Cancers are clonal cell lineages that arise due to somatic changes that promote cell proliferation and survival (Stratton et al, 2009). Despite the observation that leukaemic cells are typically transmitted between individuals from the same species, on occasion they can infect and propagate across populations from a second, different bivalve species (Metzger et al, 2016; Yonemitsu et al, 2019). These cancers represent a potential threat for the ecology of the marine environment, which argues for the necessity of their identification and characterization for their monitoring and prevention. We use multiplatform next-g­ eneration genome sequencing technologies, including Illumina short reads and Oxford Nanopore long reads, together with cytogenetics, electron microscopy, and cytohistological approaches to identify, characterize, and decipher the evolutionary origin of a new marine leukaemia that is transmitted between two different clam species that inhabit the Seas of Southern Europe, namely warty venus (Venus verrucosa) and striped venus (Chamelea gallina)

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