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Genomics unveils the evolution of a cancer transmitted at sea

  • USC CiMUS researchers have sequenced for the first time the genomes of transmissible cockle cancers, revealing an unstructured genome not observed in other cancers and mechanisms used by cancer cells to avoid extinction.
  • The study sheds light on several aspects of the evolution of these tumours: from the tissue of origin to mutations similar to those found in human cancers.
  • This research, published today in Nature cancer, is part of the Scuba Cancers project led by CiMUS principal investigator Jose Tubío and funded by the European Research Council (ERC) with €1.5M.

 

Contagious cancers have only recently been discovered thanks to advances in the field of genetics that allow us to determine in which individual a cancer cell originated. Contagious cancers are currently known only in dogs, Tasmanian devils and several marine species. For the first time, transmissible cancers in cockles that can spread through water have been sequenced, uncovering new insights into how these cancers have spread among animal populations for hundreds, possibly thousands, of year.

The study, conducted by CiMUS researchers at the University of Santiago de Compostela and collaborators from several countries, found that these cockle tumours are highly genetically unstable. The work found that these cockle tumours have a highly unstructured genome, allowed them to describe the tissue in which these contagious cancers originated and some mechanisms that contagious cancer cells use to prevent their extinction.  

The importance of this study has led the journal Nature Cancer, which until now only included studies on humans or, at most, on model organisms, to publish for the first time a study carried out on an invertebrate species that does not represent a typical model, such as the cockle. The research shares pages in this journal with another study of similar characteristics, but carried out on another species, the North American clam.

The team led by Jose Tubío also created the first high quality reference genome of the cockle that will allow future studies on other genetic questions of the species.

 

Cancers that can survive high levels of chromosomal instability

Cockles belong to one of the oldest groups of animals on Earth, the bivalve molluscs, which have inhabited the Earth for more than 500 million years and first appeared about 300 million years before the dinosaurs. These animals can contract transmissible cancers that are spread by live cancer cells, which are passed from one cockle to another through seawater. The cancers cannot be transmitted to humans and only spread between susceptible cockles.

This study focused on the common cockle (Cerastoderma edule) and researchers collected around 7,000 cockles from 36 locations in 11 countries across the European and North African coastline, from Morocco to Russia, in the search for these tumours, finding infected animals in Spain, Portugal, France, England and Ireland. Interestingly, the researchers also identified several cockles that had unexpectedly been co-infected by cells from two types of cancer at the same time.

The most unexpected finding was that these cockle tumours had a highly unstructured genome. Cancer cells within a single tumour contain very different numbers of chromosomes, something not seen in other contagious cancers. Some cells contained as few as 11 chromosomes and others as many as 354, while the number of chromosomes in the healthy cells of a normal cockle is always 38. This is surprising, as human cancer cells cannot survive high levels of chromosomal instability, although moderate levels often make tumours more likely to spread to other organs and become resistant to treatment. The researchers will continue to study the genomics of these cancers to understand how contagious cockle cancer cells survive the effects of genomic instability to understand this in all forms of cancer, including human cancer. They also observed a mutational signature described in the human brain and myeloid tumours.


Ancient tumours

Genetic analysis of tumour evolution also allowed the researchers to find strategies that cancer uses to avoid extinction, for example, evidence that cancer cells have stolen mitochondria (the small organelles that generate the cell's energy) from their cockle hosts at least seven times in the past.

As for the origin, the researchers found that the two contagious cancers in cockles are leukaemias, i.e. they originated in the haemolymph tissue (the "blood" of cockles). This suggests that the cancer takes advantage of the opportunity offered by the haemolymph to spread throughout the body. While it is difficult to accurately estimate the age of cockle cancers, the findings of this study suggest that these cancers probably arose centuries or even millennia ago.

In conclusion, these contagious cancers are thought to have originated in the haemolymph, and have spread slowly through European cockle populations by accumulating diverse mutations and occasionally capturing mitochondria from host cells as replacements for their own when damaged.

These results have been generated in the framework of the European Scuba Cancers project (www.scubacancers.org) which was funded by the European Research Council (ERC) with 1.5 million euros to investigate the genetic causes that cause a cancer cell to spread from one individual to another.

 

Reference scientific article:

A.L. Bruzos, M. Santamarina, D. Garcia-Souto, et al. (2023). Somatic evolution of marine transmissible leukaemias in the common cockle, Cerastoderma edule. Nature Cancer. DOI: 10.1038/s43018-023-00641-9

 

About CiMUS

The Singular Centre for Research in Molecular Medicine and Chronic Diseases (CiMUS) of the University of Santiago de Compostela is part of the network of research centres with a new organisational and operational model, which constitutes the fundamental element of the R&D strategy of the CAMPUS VIDA project (Campus of International Excellence, MEC-MICINN, 2009). The mission of CiMUS is to carry out basic research of proven quality, with the aim of achieving advances in the prevention, understanding and treatment of chronic disease. The centre has been awarded CIGUS recognition by the Xunta de Galicia, which accredits the quality and impact of its research. More information on the website https://cimus.usc.gal/ or follow us on social media @cimususc (Twitter, Instagram and LinkedIn).