Abstract PR017: Progression and regression dynamics of bivalve transmissible neoplasia in the soft-shell clam (Mya arenaria) after both natural and experimental exposure

Abstract

Abstract In nature, cancer is not typically contagious – cancer lives and dies within a host. However, there are three known forms of clonal cancer lineages, in which the cancer cells themselves spread throughout populations by “jumping” from one animal to another. In mammals, there are two species known to be affected by these transmissible cancers – Tasmanian devils (Tasmanian Devil Facial Tumor Disease) and dogs (Canine Transmissible Venereal Tumor). In bivalves, transmissible cancers are found in at least six different species around the world, in which there are at least seven independently derived clonal neoplastic lineages. Mya arenaria (the soft-shell clam) is the first of these bivalve species confirmed to be affected by a Bivalve Transmissible Neoplasia (BTN). BTN was originally described as disseminated neoplasia when first documented in the 1970s. This disease is characterized by high numbers of rounded, polyploid, non-adherent neoplastic cells in the circulatory fluid (hemolymph) of animals that later disseminate into tissues during the final stages of disease, often proving fatal. In this emerging field, there is still much that is unknown regarding the dynamics of disease progression in vivo. I sought to define these dynamics for the first time. I analyzed hemolymph samples from both naturally infected and experimentally infected soft-shell clams, collected from Maine, USA, over the course of disease progression. Every two weeks, hemolymph was drawn from each animal, and the DNA was analyzed using a cancer-specific qPCR assay, which quantifies the copy number of a cancer-specific target (Steamer) and a control target (N1N2). I used the two values to determine the fraction of neoplastic cells found in the hemolymph of each animal at every two-week timepoint. I have observed three main disease outcomes for both naturally and experimentally infected animals - 1) progression to death; 2) regression; and 3) long-term non-progression. My observation of significant regression and non-progression in clams exposed to BTN contrasts earlier reports suggesting near complete lethality of the disease. This finding may suggest that clam populations have evolved resistance to this cancer. Interestingly, I additionally observed a consistent long latent period after injection in the experimentally infected animals where neoplastic cells were undetectable in the hemolymph for a period of 16-20 weeks before progression. Based on my findings of this latent period, where no cancer is detectable in the hemolymph of infected animals, I hypothesize that the cells may be engrafting into a solid tissue rather than solely dividing and circulating in the hemolymph itself as originally hypothesized. These findings are a significant starting point in understanding how BTN can transmit both within individuals and throughout populations, potentially providing remarkable insight into cancer evolution and host resistance. Citation Format: Rachael M. Giersch, Marisa A. Yonemitsu, Samuel F.M. Hart, Michael J. Metzger. Progression and regression dynamics of bivalve transmissible neoplasia in the soft-shell clam (Mya arenaria) after both natural and experimental exposure [abstract]. In: Proceedings of the AACR Special Conference on the Evolutionary Dynamics in Carcinogenesis and Response to Therapy; 2022 Mar 14-17. Philadelphia (PA): AACR; Cancer Res 2022;82(10 Suppl):Abstract nr PR017.