Abstract B029: Centuries of genome instability and evolution in soft-shell clam (Mya arenaria) transmissible cancer

Abstract

Abstract Transmissible cancers are infectious parasitic clones that metastasize to new hosts, living past the death of the founder animal in which the cancer initiated. Using genomic and transcriptomic analyses, we investigated the evolutionary history of a recently identified transmissible cancer lineage that has spread though the soft-shell clam (Mya arenaria) population. We first assembled a chromosome-scale soft-shell clam reference genome and characterized somatic mutations in the cancer lineage, discovering a novel mutational signature that estimates the lineage to be >200 years old and observing a wide variety of mutation types indicative of an extremely unstable cancer genome. We next quantified gene expression, observing differential expression of stereotypical cancer hallmarks in addition to key pathways that may have facilitated the cancer’s ability to survive seawater transfer to new hosts and evade immune rejection. Finally, we developed genetic assays to track bivalve transmissible neoplasia in the soft-shell clam and identify a novel lineage in the Baltic clam (Macoma balthica). Taken together, this study reveals the long-term survival of an invertebrate cancer lineage and identifies adaptive mechanisms to evade physical and immune barriers to cancer transmission, which may have been facilitated in part by the adaptive potential of its unstable genome. Citation Format: Samuel F.M. Hart, Michael J. Metzger. Centuries of genome instability and evolution in soft-shell clam (Mya arenaria) transmissible cancer [abstract]. In: Proceedings of the AACR Special Conference in Cancer Research: Translating Cancer Evolution and Data Science: The Next Frontier; 2023 Dec 3-6; Boston, Massachusetts. Philadelphia (PA): AACR; Cancer Res 2024;84(3 Suppl_2):Abstract nr B029.