Ozkan, DidemAkin, Dilara Fatma2026-04-212026-04-2120262602-30402602-303210.17826/cumj.1850575https://hdl.handle.net/123456789/9104https://doi.org/10.17826/cumj.1850575Purpose: This study investigates the role of the SPIN1 gene from a pan-cancer perspective. Materials and Methods: Genomic data from 10,967 TCGA pan-cancer samples were analyzed to evaluate SPIN1's mutation profile, expression patterns, protein interactions, drug sensitivity, and survival associations. The functional impact of mutations was assessed using PolyPhen-2, SIFT, Mutation Assessor, AlphaMissense, and MUpro. Expression and survival data were obtained from TIMER2.0 and GEPIA, drug sensitivity from GSCALite, and protein-protein interactions from STRING and GeneMANIA. Results: Within the TCGA pan-cancer cohort, a total of 52 somatic mutations were identified in the SPIN1 gene of which 44 were missense mutations, representing 84.6% of all detected variants. The overall somatic mutation frequency of SPIN1 was approximately 0.4%. A substantial proportion of mutations clustered within functionally relevant regions, particularly the intrinsically disordered region (IDR) and the Tudor domains, which are associated with epigenetic regulation and DNA damage response. In silico stability analyses indicated that variants such as p.R158H and p.I253M were associated with a marked reduction in protein stability. Gene expression analyses revealed that SPIN1 was significantly upregulated in AML, breast, gastric, liver, lung, pancreatic and esophageal cancers, with elevated expression showing a trend toward unfavorable prognosis across multiple cancer types. Protein-protein interaction analyses demonstrated strong functional associations between SPIN1 and histone H3 variants as well as members of the SPIN protein family. Conclusion: These findings suggest that SPIN1 is a key regulator in cancer biology and may serve as a potential target for future cancer therapies.eninfo:eu-repo/semantics/openAccessMutationEpigeneticHistone ReaderSPIN1Pan-Cancer AnalysisArticle