A new study reveals unexpected levels of genomic instability not seen in other cancers and how these cancers have spread for hundreds, possibly thousands, of years.
For the first time, scientists have decoded the genomes of marine cancers that spread through water in shellfish, uncovering a remarkable degree of genetic fluctuation that sets them apart from other known cancers.
The team of researchers from institutions like the Wellcome Sanger Institute and the CiMUS research center at the Universidade de Santiago de Compostela, alongside international collaborators, dived deep into the transmissible cancers in cockles. These marine cancers can proliferate in water, giving clues to their potential dispersion across marine life over centuries, even millennia.
Their findings, released on 2nd October 2023 in Nature Cancer, highlighted the unique genetic fluidity of these cockle tumors. Astonishingly, the number of chromosomes within individual cancer cells of a single tumor varied dramatically, a phenomenon not observed in other cancer types.
Moreover, in a groundbreaking achievement, the research group generated the first detailed reference genome for the common cockle. This creature, belonging to one of Earth’s most ancient animal classes*, has had its genetic structure and evolutionary path charted for the first time.
By understanding how these marine cancer cells handle such genome volatility, scientists believe there’s a potential to enhance our comprehension of similar phenomena across various cancer types, including those in humans. This knowledge can also aid in safeguarding cockle populations down the line.
Although cockles have been on the planet far longer than dinosaurs, they are susceptible to contagious cancers, specifically bivalve transmissible neoplasia (BTN). These cancers, which don’t affect humans, are transmitted among cockles via seawater.
BTN primarily targets the cockle’s immune cells, resulting in a condition resembling leukemia. This condition, known to have eight distinct types, spreads within the organism and is typically fatal. The global existence of this disease spans clams, cockles, and mussels.
This particular study spotlighted the commonly consumed cockle, Cerastoderma edule, which thrives along the coastlines of Europe and northwest Africa. The researchers developed a detailed genome of this species, a critical move for understanding the evolution of its cancers.
Dr. Zemin Ning of the Wellcome Sanger Institute emphasized, “Marine transmissible cancers are less well-understood than contagious cancers in species like dogs and Tasmanian devils, due to the lack of robust reference genomes of the animals they impact. Our study provides the first quality reference genome of the common cockle, which is vital if we are to uncover and understand the genetic changes seen in cockle cancers. To keep learning about transmissible cancers, it is important to continue to provide quality genetic data on the affected species.”
Researchers from various institutions embarked on an extensive project, gathering about 7,000 cockles from 36 diverse spots across 11 nations like Spain, Ireland, and Morocco. Of these, 61 cockle tumors were genetically mapped, revealing two distinct forms of BTN cancers, distinguishable under microscopic observation.
Interestingly, several cockles appeared to have dual infections, harboring cells from both cancer types simultaneously.
The team’s genetic investigations into the tumor lineage detected various genetic shifts. For instance, the cancerous cells seem to have absorbed mitochondria, the energy-producing structures within cells, from their cockle hosts on at least seven occasions in history.
Estimating the age of these cockle cancers is tricky, but the research infers their emergence might date back several centuries, if not longer. These cancers seem to have propagated gradually among European cockle communities, at times commandeering mitochondria from host cells, particularly when their own got impaired.
Dr. Alicia Bruzos, once affiliated with CiMUS – Universidade de Santiago de Compostela during the research, remarked, “Tumours 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.”
A striking discovery was the pronounced genetic instability of BTN tumor genomes. There were significant disparities in the chromosome count, both among different tumors and within the same tumor. For context, while a typical cockle cell has 38 chromosomes, some tumor cells have as few as 11 or as many as 354.
This kind of “chromosomal instability” surpasses what’s seen in human cancers. It implies that a stable genetic makeup might not be crucial for these marine cancers’ longevity. This defies conventional understanding since human cancer cells usually can’t withstand excessive genetic instability.
Gleaning more about how these BTN cells cope could offer novel tactics to combat human cancers.
Dr. Daniel Garcia-Souto, formerly with the Wellcome Sanger Institute and now at CiMUS-Universidade de Santiago de Compostela, shared, “Our study showed that the cells in these cockle tumors contain highly variable amounts of genetic material, which is very unusual compared to other types of cancer. 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.”
Furthermore, the significance of understanding BTN is underscored by its potential to safeguard cockle communities. At times, contagious cancers, along with other environmental threats like pollution and rising ocean temperatures, can lead to mass die-offs, wiping out over 90% of cockles in certain regions.
Such a drastic reduction in cockle numbers jeopardizes the food chain, and employment in fisheries, and has broader ecological repercussions. Future endeavors to study infectious cancers in cockles could guide preventive measures against these devastating events, which seem to be on the rise.
Dr. Adrian Baez-Ortega from the Wellcome Sanger Institute emphasized, “Cockles are an important part of life for many people in Europe, and are a crucial part of coastal ecosystems. They have been around for many millions of years, but now they face a variety of threats of which transmissible cancers are only one example. 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.”
Source: 10.1038/s43018-023-00641-9
Image Credit: Getty