Novel prognostic biomarkers in central neurocytoma

Central neurocytomas (CN) are intraventricular brain tumors predominantly occurring in young adults. Although prognosis is usually favorable, tumor recurrence is common, particularly following subtotal resection (STR). Currently, the risk of progression is evaluated using histopathological criteria, such as atypical features and elevated Ki67 proliferation index. However, these markers lack consistent definitions and application. Genome-wide DNA methylation profiles were examined in 136 tumors histologically classified as CN. Clinical and histopathological characteristics were assessed in 93 and 90 cases, and whole-exome sequencing was conducted in 12 cases. Clinical and molecular characteristics were integrated into a survival model to predict progression-free survival (PFS). A diagnosis of CN was epigenetically confirmed in 125 of 136 cases (92%). No DNA methylation subgroups associated with risk were identified, but global DNA hypomethylation emerged as a hallmark feature of CN. Hypomethylation at the FGFR3 locus, accompanied by increased FGFR3 protein expression, was observed in 97% of cases. Exome-sequencing revealed BCR frameshift mutations in 3/12 cases. Gross total resection was associated with significantly improved PFS compared to subtotal resected tumors (STR), while patients undergoing STR benefited from adjuvant radiotherapy (p = 0.00088). Younger patients were identified as having a higher risk of recurrence (p = 0.026). Patient age and treatment strategy were key factors influencing survival outcomes in this cohort. These findings underscore the importance of closer follow-up for younger patients and recommend radiotherapy for STR cases. Furthermore, FGFR3 represents a hallmark feature and potential therapeutic target warranting further investigation. The cohort (125 cases) comprises 111 primary and 22 recurrent samples (of which 8 were matched with primary samples, including 2 samples from second recurrence).