A Cancer Spreading Through a Fish Population: The Mystery of Brown Bullhead Melanoma

Beginning in 2012, large numbers of brown bullheads (Ameiurus nebulosus) with dark skin lesions were observed in Lake Memphremagog, which straddles the border between Vermont in the United States and Quebec in Canada. Some lesions appeared as flat, darkly pigmented patches, while others developed into conspicuous raised masses, including lesions around the eyes, opercula and mouth. Histopathological examination confirmed that the raised lesions were malignant melanomas. Among fish sampled between 2014 and 2017, the prevalence of these lesions reached 23–37%, far exceeding the rates reported from other bodies of water.

Lake Memphremagog（Image source：Curd EE et al. (2026)， CC BY-NC-ND 4.0 ）

Brown bullhead (Ameiurus nebulosus)（Image source：Unknown，CC0 1.0 ）

Melanoma lesions（Image source：Curd EE et al. (2026)， CC BY-NC-ND 4.0 ）

The outbreak was initially viewed as a warning sign of deteriorating water quality. Brown bullheads are widely distributed across eastern North America and are often used as indicators of aquatic environmental quality. In 2011, Tropical Storm Irene caused extensive flooding in the region, raising the possibility that surface runoff had carried contaminants into the lake. Researchers therefore had to consider whether carcinogenic chemicals or infectious pathogens might be responsible. Because Lake Memphremagog supplies drinking water to more than 175,000 people, the cause of cancer in the fish was relevant not only to wildlife health but also to public concerns about environmental safety.

Genomic analyses of the tumours later pointed to a far more unusual explanation: the cancer cells themselves might be spreading from one fish to another. Conventional cancers arise when cells within an individual accumulate mutations. Tumours that develop independently in different animals therefore remain genetically most similar to their respective hosts and generally cannot survive after entering another individual. A transmissible cancer, by contrast, originates in a single founder animal. Cancer cells leave that original host, enter other individuals, continue proliferating and form new tumours. The genomes of these tumours retain a close relationship to the original host and remain clearly distinct from the genomes of their subsequent hosts, allowing the cancer to persist as a parasitic lineage composed of living cells.

The researchers compared tumours from affected brown bullheads with normal tissues from the same fish. They also included healthy fish from Lake Memphremagog and reference populations from other waters in Vermont, New Hampshire and Maine. The dataset included RNA-sequencing samples collected in 2015 and whole-genome sequencing data obtained in 2019 and 2023. The sampled lesions ranged from flat melanistic areas containing proliferating melanocytes but no developed tumour mass to advanced melanomas in which the normal architecture of the skin had disappeared. In severe cases, tumour cells had invaded the underlying muscle and, in a small number of fish, metastasized to other organs.

The first major line of evidence came from mitochondrial DNA. All tumour samples showed heteroplasmy, meaning that two or more slightly different mitochondrial DNA sequences were present within the same tissue. The tumours contained approximately 32–37 variant sites relative to normal tissue from their hosts. Many of the same variants occurred in tumours collected from different fish, indicating that these tumours had inherited characteristic mitochondrial DNA variants from the cancer cells of the same original host.

Mitochondrial DNA from different tumours is highly similar but differs from the normal tissue of the respective hosts. (a) A phylogenetic tree constructed from mitochondrial DNA sequences. Red indicates normal tissue (N) from affected fish, blue indicates tumour tissue (T) from the same fish, and grey indicates healthy reference fish from other bodies of water. Samples positioned on nearby branches have more similar mitochondrial DNA sequences. The labels at the tips of the tree are tissue sample identifiers. (b) Single-nucleotide variants in the mitochondrial DNA of each sample relative to the healthy reference fish HL4. Each short line represents a variant site. The presence of variants at many of the same positions across different tumour samples indicates that the tumours originated from the same cancer cell lineage（Image source：Curd EE et al. (2026)， CC BY-NC-ND 4.0 ）

The researchers then used mitochondrial genome sequences to construct a phylogenetic tree. Tumours sampled in 2015, 2019 and 2023 all formed a single monophyletic clade. In other words, their mitochondrial genomes shared a common ancestor, showing that the cancer cells belonged to one clonal lineage that had already arisen before 2015.

The nuclear genome provided further support. The researchers analysed 686,296 single-nucleotide variant sites, and the tumour samples once again formed a distinct monophyletic clade in the phylogenetic analysis. Among 245,189 tumour-specific variants, 59% were found in tumours from at least 14 brown bullheads. Such extensive sharing indicates that the tumours have a highly consistent common origin. Nuclear genome analysis also showed that the tumour cells were genetically more closely related to healthy reference fish from New Hampshire and Maine than to most brown bullheads from Lake Memphremagog. This pattern suggests that the cancer lineage may have originated outside the lake before entering the local population.

A neighbour-joining phylogenetic tree constructed from single-nucleotide variants in the nuclear genome. Red indicates normal tissue from 16 affected fish, blue indicates melanistic lesion tissue from the same fish, and grey indicates 12 healthy reference fish collected from other locations. Samples positioned on nearby branches have more similar patterns of DNA variation. Tumour samples from different fish cluster together as a distinct group rather than clustering with normal tissue from their respective hosts, supporting the conclusion that these tumours originated from the same cancer cell lineage（Image source：Curd EE et al. (2026)， CC BY-NC-ND 4.0 ）

Exactly how the cancer cells pass between fish remains unknown. This type of melanoma has not been documented in fish younger than reproductive age, which may indicate a long latent period or a connection with reproduction or ageing. During the spawning season, adult brown bullheads gather within relatively small areas and come into frequent physical contact, creating opportunities for the direct transfer of cancer cells. The aquatic environment may also allow shed tumour cells to reach a new host through the gills, skin or mouth.

Brown bullheads are scaleless, benthic fish that spend much of their time close to the lake bottom. Cancer cells deposited in the sediment might therefore come into contact with passing fish. Reproductive hormones also modulate immune responses in fish, while pollutants or hormonal imbalances could further weaken their ability to resist tumour cells. Under such conditions, foreign cancer cells may be more likely to survive, engraft and continue proliferating in a new host.

The cancer lineage was not present at conspicuous levels before 2012, yet by 2015 it had affected approximately 30% of the brown bullheads in Lake Memphremagog, indicating rapid transmission through the population. Whether the disease is lethal, whether tumours can regress spontaneously and whether the lineage has already spread to other North American waters remain unknown. The consequences of transmissible cancers vary greatly among host species. Tasmanian devil (Sarcophilus harrisii) facial tumour disease is nearly always fatal and has contributed to population declines of about 90%. Canine transmissible venereal tumours commonly regress on their own. Bivalve populations, meanwhile, may persist despite widespread transmissible cancer, although localized mortality events have also been recorded.

Melanomas in North American brown bullheads were reported more than a century ago. Those earlier cases may have belonged to the same ancient cancer lineage, represented a separate transmissible lineage, or simply been conventional cancers. Future studies will require broader geographic sampling, molecular-clock estimates of the lineage's age and clearer measurements of its lethality and transmissibility. These data will be essential for determining whether restrictions on fish movement, stocking or other human activities are needed to prevent viable cancer cells from being carried into previously unaffected waters.

Author: Shui-Ye You

Reference:

Curd EE et al. (2026). Brown bullhead catfish melanoma represents a novel transmissible cancer. Nature.