Abstract A003: Genome evolution of a transmissible cancer in the soft-shell clam (Mya arenaria)

Abstract

Abstract A small number of transmissible cancer lineages exist in which cancer cells metastasize repeatedly to new hosts and live past the death of their original hosts. Transmissible cancers have been observed in the dog, Tasmanian devil, and most recently in numerous bivalves species, including one lineage that has spread through the soft-shell clam (Mya arenaria) population along the east coast of North America. We assembled a highly contiguous 1.2 Gb soft-shell clam reference genome and characterized the genome evolution of this transmissible cancer lineage. Our analyses confirm that all cancer samples descended from a single founder clam, but cluster in two geographically separated sub-lineages. In both sub-lineages, we observe high somatic mutation density, widespread copy number gain, structural rearrangement and transposable element activity, all indicative an unstable cancer genome. We also discovered a novel mutational signature generating mutations at a stable rate, predicting the cancer to be 344 to 877 years old and indicating it spread undetected long before it was first observed in the 1970s. Citation Format: Samuel F.M. Hart, Rachael M. Giersch, Marisa A. Yonemitsu, Brian Beal, Stephen P. Goff, Michael J. Metzger. Genome evolution of a transmissible cancer in the soft-shell clam (Mya arenaria) [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 A003.