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Aims: Dermatomyositis (DM) is a progressive, idiopathic inflammatory myopathy with poorly understood pathogenesis. A hallmark of DM is an increased risk for developing breast, ovarian, and lung cancer. Since autoantibodies against anti-TIF-1-γ, a member of the tripartite motif (TRIM) proteins, has a strong association with malignancy, we examined expression of the TRIM gene family to identify pathways that may be contributing to DM pathogenesis. Materials and methods: We employed the Search Tag Analyze Resource for GEO platform to search the NCBI Gene Expression Omnibus to elucidate TRIM family gene expression as well as oncogenic drivers in DM pathology. We conducted meta-analysis of the data from human skin (60 DM vs 34 healthy) and muscle (71 DM vs 22 healthy). Key findings: We identified genes involved in innate immunity, antigen presentation, metabolism, and other cellular processes as facilitators of DM disease activity and confirmed previous observations regarding the presence of a robust interferon signature. Moreover, analysis of DM muscle samples revealed upregulation of TRIM14, TRIM22, TRIM25, TRIM27, and TRIM38. Likewise, analysis of DM skin samples showed upregulation of TRIM5, TRIM6, TRIM 14, TRIM21, TRIM34, and TRIM38 and downregulation of TRIM73. Additionally, we noted upregulation of oncogenes IGLC1, IFI44, POSTN, MYC, NPM1, and IDO1 and related this change to interferon signaling. While the clinical data associated with genetic data that was analyzed did not contain clinical data regarding malignancy in these cohorts, the observed genetic changes may be associated with homeostatic and signaling changes that relate to the increased risk in malignancy in DM. Significance: Our results implicate previously unknown genes as potential drivers of DM pathology and suggest certain TRIM family members may have disease-specific roles with potential diagnostic and therapeutic implications.