Phenotypic variation in tumors may arise from environmental variation or differences in host immune response that were undetectable in lip biopsies, potentially reflecting variation in host-tumor coevolutionary relationships among sites that differ in the time since DFTD arrival. ConclusionsĮxpression variation among localities may reflect morphological differences in tumors that alter ratios of normal-to-tumor cells within biopsies. No mRNA sequence variants were associated with expression variation. Pathways that were up- or downregulated in DFTD tumors relative to normal tissues exhibited the same patterns of expression with greater intensity in tumors from localities that experienced DFTD for longer. However, 4088 genes were differentially expressed in tumors among our sampling localities. We found minimal variation in gene expression of devil lip tissues, either with respect to DFTD infection status or sex. We sequenced transcriptomes from healthy and DFTD-infected devils, as well as DFTD tumors, to characterize host responses to DFTD infection, identify differing host-tumor molecular interactions between sexes, and investigate the extent to which tumor gene expression varies among host populations. However, the processes underlying this variation remain unknown. Despite initial predictions of extinction, populations have persisted at low levels, due in part to heterogeneity in host responses, particularly between sexes. Tasmanian devils have been impacted dramatically by a transmissible cancer (devil facial tumor disease DFTD) that has led to widespread population declines. More generally, transcriptomics studies of infectious diseases characterize interactions between host, pathogen, and environment to better predict population-level outcomes. In oncology, transcriptomics studies, which characterize the expression of thousands of genes, have identified processes leading to heterogeneity in cancer phenotypes and individual prognoses. Transmissible cancers lie at the intersection of oncology and infectious disease, two traditionally divergent fields for which gene expression studies are particularly useful for identifying the molecular basis of phenotypic variation.
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