GEOapplication/xmlftp://ftp.ncbi.nlm.nih.gov/geo/series/GSE345nnn/GSE345045/primaryOK200OtherHomo sapiensOtherhttps://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE345045GEOGSEfalseComparative transcriptomic and immune profiling identifies a shared molecular identity in clear cell odontogenic carcinoma and hyalinizing clear cell carcinoma [1]Clear cell odontogenic carcinoma (CCOC) and hyalinizing clear cell carcinoma (HCCC) are rare head-and-neck malignancies with recurrent EWSR1::CREB family fusions that show overlapping morphology and immunophenotype, but whose molecular relationship to each other and to relevant differential diagnoses has remained poorly defined due to tissue rarity. No standardized systemic therapy exists for either tumor. We performed spatial transcriptomic profiling (NanoString GeoMx Whole Transcriptome Atlas), multiplex immunofluorescence, and RNA in situ hybridization on 80 FFPE tumor samples spanning CCOC, HCCC, clear cell sarcoma, and six additional head-and-neck comparator tumors (squamous cell carcinoma, ameloblastoma, adenoid cystic carcinoma, myoepithelial carcinoma, Ewing sarcoma, and prostate carcinoma as an outgroup). CCOC and HCCC showed highly concordant, overlapping global transcriptomic profiles and converged on a shared epithelial-secretory program, with strong enrichment of IGF2 and candidate therapeutic targets including TACSTD2 (TROP2), FGFR2, FOLR1, KDR, MSLN, and MUC1. Clear cell sarcoma, despite sharing the same fusion family, remained transcriptomically distinct. Immune profiling revealed a cold tumor microenvironment in CCOC/HCCC, with low B2M and HLA class I expression, sparse lymphoid infiltration, and minimal PD-L1 expression, consistent with impaired antigen presentation. These findings indicate that CCOC and HCCC share a common molecular identity distinct from other relevant head-and-neck tumors, particularly myoepithelial carcinoma and squamous cell carcinoma, providing a framework to improve diagnostic classification and prioritize therapeutic targets for these exceptionally rare cancers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9992097GSM9992098GSM999180037309345045Homo sapiens