PATH-105. GTAKA (Glioneuronal Tumor with ATRX Alteration, Kinase Fusion, and Anaplastic Features): A Novel Central Nervous System Entity with Distinct Clinicopathologic, Molecular Profiles, and Prognosis

OBJECTIVE To investigate the clinicopathological, immunohistochemistry, molecular characteristics, and prognosis of new entity-GTAKA (Glioneuronal tumor with ATRX alteration, kinase fusion and anaplastic features). METHODS Seven GTAKA cases were collected and analyzed through histomorphological evaluation, immunohistochemistry (IHC), DNA methylation profiling, DNA&RNA sequencing and prognosis. A review of 28 reported cases (including our 7 cases) was conducted to compare clinicopathological and molecular features. RESULTS GTAKA predominantly affected children or young adults (median age: 18), with supratentorial localization. Histopathological patterns were identified: (1)Central neurocytoma-like; (2)Non-neurocytoma-like. IHC character: GFAP positive (7/7,100%), Olig2 positive (7/7,100%), Syn partly positive (7/7,100%), ATRX negative (5/7,71.4%), NKX2.2 positive (7/7,100%) and SOX10 positive (7/7,100%). Molecular profiling revealed all the cases have NTRK fusion and ATRX mutation. Methylation analysis revealed all the 7 cases were classified as “GTAKA” cluster. Survival outcome revealed GTAKA was worse than atypical central neurocytoma in our cohort (median OS: 35 VS. 78 months, P<0.001). CONCLUSION CNS GTAKA tumors exhibit distinct clinicopathological and molecular profiles, with DNA methylation profiling aiding accurate classification. The double strong positivity of NKX2.2 and SOX10 can be used as an immunohistochemical feature to assist in the diagnosis of GTAKA. Targeted NTRK inhibition is a promising therapeutic option. This study underscores the importance of recognizing GTAKA as a unique entity, providing critical insights for classification, prognostication, and personalized treatment.