{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,25]],"date-time":"2026-05-25T15:05:02Z","timestamp":1779721502639,"version":"3.53.1"},"reference-count":23,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,4,28]],"date-time":"2026-04-28T00:00:00Z","timestamp":1777334400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Oncol."],"abstract":"<jats:p>TNF \u03b1 inhibitors such as adalimumab are widely used for autoimmune diseases, yet their long-term impact on tumor development in genetically susceptible individuals remains incompletely defined. Glioblastoma (GBM) is an aggressive IDH wild-type tumor with recurrent molecular alterations; however, comprehensive genomic analyses of GBM arising in patients treated with TNF-\u03b1 inhibitors are extremely limited. We examined the genomic features of a GBM developing after prolonged TNF-\u03b1 inhibitor therapy to explore potential links between TNF-\u03b1 blockade, and tumor evolution. Tumor tissue was analyzed using immunohistochemistry, targeted next-generation sequencing, and copy number analysis performed at two independent clinical laboratories. Genomic findings were interpreted in the context of TNF \u03b1 pathway biology and tumor microenvironment interactions relevant to GBM progression. The tumor demonstrated GFAP and OLIG positivity, a Ki-67 index of 45%, and strong p53 expression (&amp;gt;90%). Genomic profiling revealed hallmark alterations of IDH wild-type GBM, including CDKN2A\/B deletions, PTEN deletion, and a TP53 mutation. Additional findings included a KDM6A frameshift variant, an ATRX variant of uncertain significance, and loss of PDPK1. No TERT promoter mutation was detected, suggesting a potential alternative telomere maintenance mechanism. The combination of PTEN loss, TP53 mutation, and CDKN2A\/B deletion is consistent with an aggressive molecular phenotype associated with immune evasion. This case highlights genomic features of an IDH\u2212wild\u2212type glioblastoma arising after prolonged TNF\u2212\u03b1 inhibitor exposure. While no causal inference can be made, this analysis identifies both canonical and atypical genomic alterations in a GBM arising after prolonged TNF-\u03b1 targeted therapy. This temporal relationship provides a basis for studying possible convergence between TNF-\u03b1 signaling and GBM-associated pathways, and underscores the importance of genomic risk stratification when considering TNF-\u03b1 inhibitor therapy.<\/jats:p>","DOI":"10.3389\/fonc.2026.1788983","type":"journal-article","created":{"date-parts":[[2026,4,28]],"date-time":"2026-04-28T04:55:47Z","timestamp":1777352147000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Genomic profile of an IDH\u2212wild\u2212type glioblastoma diagnosed following TNF\u2212\u03b1 inhibitor therapy: a molecular case study"],"prefix":"10.3389","volume":"16","author":[{"given":"Suryanarayan","family":"Mohapatra","sequence":"first","affiliation":[{"name":"Internal Medicine, Kaiser Permanente - Mid-Atlantic Permanente Medical Group","place":["Silver Spring, MD, United 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