Transmissible Cancers in Cockles Analyzed Through Genome Sequencing

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Scientists have sequenced the genomes of contagious cancers found in cockles, discovering exceptional levels of genomic instability not typically found in other cancers.

These transmissible cancers, marine variants that can propagate via water, have been found to persist across cockle populations for possibly thousands of years. A collaborative research effort between the Wellcome Sanger Institute, the CiMUS research center at Universidade de Santiago de Compostela in Spain, and various international institutions observed that these cockle tumors are highly genetically unstable. This results in the cancer cells within a single tumor exhibiting widely varying numbers of chromosomes, a phenomenon unique to these cancers.

The study, published in Nature Cancer, includes the creation of the first high-quality reference genome of the common cockle. This species is among the oldest animal groups, with cockles being small shellfish belonging to bivalve mollusks, a category that has existed for over 500 million years.

Interestingly, cockles can acquire contagious cancers that disperse via living cells through seawater, transferring from one cockle to another. Designated as bivalve transmissible neoplasia (BTN), these cancers infect the cockle's immune cells and exhibit traits akin to leukemia. To date, eight distinct BTN types have been detected in clams, cockles, and mussels globally.

For this study, the focus was on the common cockle (Cerastoderma edule), a species found along the coasts of Europe and northwest Africa. Dr. Zemin Ning of the Wellcome Sanger Institute mentioned, “Our study provides the first quality reference genome of the common cockle, which is vital if we are to understand the genetic alterations present in cockle cancers.”

From around 7,000 cockles collected across 36 sites in 11 countries, the team sequenced the genetics of 61 cockle tumors. They established the existence of two distinct BTN types, with the cell types exhibiting discernible differences. Additionally, some cockles were found to be co-infected by cells from both cancer types simultaneously.

Genetic tracking of tumor evolution revealed several genetic modifications, including instances where the cancer cells acquired mitochondria from their host cockles.

Although determining the exact age of these cockle cancers is challenging, the study indicates they could have arisen centuries or even millennia ago. These cancers have possibly been spreading gradually through European cockle populations, intermittently absorbing mitochondria from host cells when their mitochondria were compromised.

Dr. Alicia Bruzos remarked on the significance of their findings, “Tumors were first found in cockles around 40 years ago, but our study is one of the first to sequence and analyze the whole genomes of these animals. We clarified the existence of two independent transmissible cancers, and we suspect that there are many more different types out there. Having a wider view of the different types of transmissible cancers can give us more insight into the conditions necessary for tumors to evolve and survive long-term.”

The research team noted the remarkable instability of the BTN tumor genomes. Chromosomal variations were evident not only between different tumors but also within the same tumor. Some cells had as few as 11 chromosomes, while others had up to 354, with a normal cockle cell having 38 chromosomes. Dr. Daniel Garcia-Souto commented, “These cancers have been undergoing extreme chromosomal changes and continuous genetic reorganization, probably for hundreds or thousands of years, which challenges the theory that cancers require stable genomes to survive long-term.”

Understanding BTN and its implications is essential for safeguarding future cockle populations. Several factors, including transmissible cancers, can combine to cause mass mortality events, decimating over 90% of cockles in a specific area. Such a loss can have repercussions on food security, employment in the fishing industry, and broader ecological impacts.

Concluding the findings, Dr Adrian Baez-Ortega from the Wellcome Sanger Institute said, “Understanding more about the origins and evolution of cockle transmissible cancers, and how their cells interact with cockle cells and the marine environment, could help protect animal populations in the future, while providing insight into how cancers can survive for thousands of years as marine parasites.”