PO-222 Molecular characterisation of low grade lymphoma in northern sea otters (Enhydra lutris kenyoni)

Abstract

IntroductionLymphoid cancers are a biologically diverse group of neoplasms. Disease aetiology is multifactorial, implicating viral and infectious agents, immune dysfunction, and genetic factors. Lymphoid cancers affect domestic and laboratory animals; among members of Mustelidae, lymphoma has been reported in domestic ferrets, yet rarely in sea otters, with only 3 reported cases since 2002. However, since 2006, 3 sea otters at the Vancouver Aquarium (British Columbia, Canada) developed lymphoma. All 3 sea otters were rescued as young animals and have lived at the aquarium for the majority of their lives. A 21 year old female was diagnosed with chronic lymphocytic leukaemia, while 2 males, aged 12 and 16, were diagnosed with lymphoma. Both males received chemotherapy before being humanely euthanized due to declining quality of life. A high rate of blood cancers in this population motivated the molecular characterisation of the most recent lymphoma.Material and methodsWhole genome sequencing was performed on peripheral blood and a lymphoma needle biopsy. The tumour biopsy was sequenced on the Illumina HiSeq X and Oxford Nanopore MinION, generating 264.5 and 4.63 passed filtered Gbp, respectively. De novo assembly was performed on the Illumina DNA and RNA data using ABySS 1.3.4. Structural variants were called with trans-abyss 1.4.10. Somatic variants were called by Strelka (v1.0.15) using matched tumour-normal samples aligned against the Enhydra lutris kenyoni reference genome. Variants were annotated by snpEFF (v4.3) using an in-house custom gene annotation database. The mutations in the sea otter tumour were subsequently compared to human and canine lymphomas.Results and discussionsThe sea otter genome contains 24 129 genes, of which 17 421 were mapped to the human genome. We identified several mutated genes with a known involvement in human lymphomas. We observed a stop-gain mutation in EP400, a paralog of human EP300. EP300 is a tumour suppressor which has been previously implicated in human Diffuse Large B-Cell and Follicular lymphomas. We also observed an indel in SPEN, a NOTCH pathway regulator, the deregulation of which is associated with human hematopoietic neoplasms.ConclusionThese observations suggest gene and pathway deregulation are a shared genetic commonality between sea otter and human lymphomas. Comparing the mutational spectrum in human, canine, and sea otter lymphoid cancers may elucidate aetiology and treatment options, and facilitate a One Health approach to neoplasia.