Abstract B002: Transmissible cancer in bivalves: Mutation and selection in cancer lineages and host genomes through hundreds of years of evolution
Notice bibliographique
Résumé
Abstract Transmissible cancers are clonal infectious cancer cell lineages that have evolved into infectious parasitic cell lines that repeatedly engraft from animal to animal through the environment. They occur in dogs, Tasmanian devils and in many species of bivalves (10 species reported so far). The bivalve transmissible neoplasia (BTN) in soft-shell clams was recently identified as transmissible, but the cancer has been observed on the east coast of North America for several decades, causing massive die-offs in populations in New England and Canada in the 1980s and 2000s of up to 90%, but it is currently maintained in those populations at a prevalence of only ∼1-5%. We have assembled a chromosome-scale reference genome for soft-shell clams and have sequenced pure samples of BTN, confirming the clonal nature of these cancers and identifying a deep split between the cancers separated geographically, with distinct sublineages in New England and Prince Edward Island. Using the high-confidence somatic SNVs that occurred since this divergence, we generated a molecular clock that estimates that this cancer lineage is approximately 400 years old. We also observed high levels of genome rearrangement and transposable element activity, as well as a unique mutational signature, likely due to the over-activity of an error-prone polymerase. By following naturally engrafted clams in the lab, we have observed that about half of clams progress to high levels of cancer followed by death, while the other half are long-term non-progressors or are cases in which cancer first grows but then regresses. We are currently conducting analyses to identify loci associated with engraftment by BTN and with severe disease, in order to identify the genetic mechanism of the blocks to cancer progression that appear to have evolved in these population of clams. In contrast to this enzootic maintenance of the disease on the east coast, we have recently discovered an outbreak of this same lineage of BTN in soft-shell clams in Puget Sound, Washington. We have recorded prevalences of >80% in two sites, and local aquaculture and communities are reporting massive die-offs. By comparing the transcriptomic response of the more resistant east coast clams and the more susceptible west coast clams, we will determine what genes are differentially expressed in clams that are able to block cancer growth. Overall, we are using the evolutionary history of these unique models of dramatically long-lived cancer cells to identify genetic mechanisms for blocking cancer. Citation Format: Michael J. Metzger. Transmissible cancer in bivalves: Mutation and selection in cancer lineages and host genomes through hundreds of years of evolution [abstract]. In: Proceedings of the AACR Special Conference in Cancer Research: Cancer Evolution: The Dynamics of Progression and Persistence; 2025 Dec 4-6; Albuquerque, NM. Philadelphia (PA): AACR; Cancer Res 2025;85(23_Suppl):Abstract nr B002.
Récupéré en direct depuis OpenAlex et désinversé. Les résumés ne sont pas conservés dans cette base de données : les index inversés représentent 8,6 Go des 9,3 Go de texte de la base, et le serveur dispose de 13 Go libres.
Comment cette classification a été obtenuedéplier
Prédiction machine sur la base complète
Imitation des enseignantsNi prévalence calibrée, ni vérité terrain. Validation humaine à venir. Le volet Gemma est une étiquette directe du modèle pour chaque travail de la base, lue sur la notice réduite au titre. Le volet Codex est un classifieur appris des 10 348 étiquettes directes de Codex et calibré sur les taux pondérés de l'échantillon; les champs sans appui suffisant ne portent aucun appel Codex. Le mode candidate est l'union des deux volets; le consensus est leur intersection. Ces sorties portent le statut machine_predicted_unvalidated et ne sont pas des étiquettes humaines.
Scores du classifieur distillé par catégorie (deux têtes)
| Catégorie | Codex | Gemma |
|---|---|---|
| Métarecherche | 0,000 | 0,001 |
| Méta-épidémiologie (sens strict) | 0,000 | 0,000 |
| Méta-épidémiologie (sens large) | 0,000 | 0,000 |
| Bibliométrie | 0,001 | 0,001 |
| Études des sciences et des technologies | 0,000 | 0,000 |
| Communication savante | 0,001 | 0,000 |
| Science ouverte | 0,000 | 0,001 |
| Intégrité de la recherche | 0,000 | 0,000 |
| Charge utile insuffisante (le modèle a refusé de juger) | 0,003 | 0,001 |
Scores machine (provisoires)
Les deux têtes enseignantes du modèle étudiant, lues sur ce travail. Un score ordonne la base pour la relecture; il n'affirme jamais une catégorie, et le statut de validation accompagne chaque rangée tel quel.
Scores de référence d'un modèle non mature (critères de maturité non atteints, 7 itérations). Un score ordonne; il n'affirme jamais une catégorie.
score_only:v0-immature-baseline · tel quel depuis la passe de notation : score_only signifie que le nombre peut ordonner les travaux, et qu'aucune étiquette de catégorie n'en découleClassification
machine, non validéePrédiction automatique; un appel candidat d’une seule source (Gemma direct ou Codex distillé), pas un consensus.
Le détail, modèle par modèle et score par score, se trouve en fin de page sous « Comment cette classification a été obtenue ».