Capicua (CIC) mutations in gliomas in association with MAPK activation for exposing a potential therapeutic target.
Medical oncology (Northwood, London, England)
california; psjhc; pacific neurosci; Capicua; Clinical oncology; Glioma; MAPK; Molecular oncology; Targeted medicine; Humans; Oligodendroglioma; Repressor Proteins; Glioma; Mutation; Treatment Outcome; Brain Neoplasms
Gliomas are the most prevalent neurological cancer in the USA and care modalities are not able to effectively combat these aggressive malignancies. Identifying new, more effective treatments require a deep understanding of the complex genetic variations and relevant pathway associations behind these cancers. Drawing connections between gene mutations with a responsive genetic target can help drive therapy selections to enhance patient survival. We have performed extensive molecular profiling of the Capicua gene (CIC), a tumor and transcriptional suppressor gene, and its mutation prevalence in reference to MAPK activation within clinical glioma tissue. CIC mutations occur far more frequently in oligodendroglioma (52.1%) than in low-grade astrocytoma or glioblastoma. CIC-associated mutations were observed across all glioma subtypes, and MAPK-associated mutations were most prevalent in CIC wild-type tissue regardless of the glioma subtype. MAPK activation, however, was enhanced in CIC-mutated oligodendroglioma. The totality of our observations reported supports the use of CIC as a relevant genetic marker for MAPK activation. Identification of CIC mutations, or lack thereof, can assist in selecting, implementing, and developing MEK/MAPK-inhibitory trials to improve patient outcomes potentially.
Neurosciences (Brain & Spine)
Darabi, Sourat; Xiu, Joanne; Samec, Timothy; Kesari, Santosh; Carrillo, Jose; Aulakh, Sonikpreet; Walsh, Kyle M; Sengupta, Soma; Sumrall, Ashley; Spetzler, David; Glantz, Michael; and Demeure, Michael J, "Capicua (CIC) mutations in gliomas in association with MAPK activation for exposing a potential therapeutic target." (2023). Articles, Abstracts, and Reports. 7478.