Ependymoma

Supratentorial ependymomas with ZFTA-RELA fusions represent a highly aggressive pediatric brain tumor subtype, yet the post-transcriptional mechanisms driving their malignancy remain unclear. This study fills a critical gap by systematically profiling miRNA expression in fusion-positive and fusion-negative supratentorial ependymomas, revealing a distinct fusion-associated miRNA signature. The identification of hsa-miR-138-5p upregulation and hsa-miR-135b-5p/hsa-miR-216a-3p downregulation, converging on key oncogenic nodes such as TERT, YAP1, RELA, and TP53, provides novel mechanistic insight into how fusion-driven miRNA dysregulation enhances epithelial-mesenchymal transition and stemness. The findings suggest that miRNA-fusion interactions play an important role in tumor aggressiveness and highlight hsa-miR-138-5p as a potential biomarker for disease progression. Clinically, the work advances understanding of fusion-driven ependymoma biology and lays the foundation for developing miRNA-based diagnostic and therapeutic strategies targeting molecular mechanisms of tumor progression.

P=N/A, N=94, Recruiting, Tata Memorial Centre | Phase classification: P3 --> P=N/A

P1/2, N=63, Active, not recruiting, Centre Oscar Lambret | Trial primary completion date: May 2025 --> Dec 2025

P1, N=71, Active, not recruiting, National Cancer Institute (NCI) | N=110 --> 71 | Trial completion date: Dec 2025 --> Jan 2027

P=N/A, N=600, Completed, West China Hospital

While H3K27M mutations are hallmark features of diffuse midline gliomas, rare cases of posterior fossa ependymomas harboring these mutations have been reported. Recent studies suggest molecular similarities between diffuse midline gliomas and posterior fossa ependymomas expressing H3K27M and EZHIP, potentially reflecting shared hindbrain developmental programs in their biological origins.

Furthermore, we found that high circRMST expression and low promoter methylation levels are associated with poor prognosis. In conclusion, this study identifies circRMST as a novel oncogene in PF EPN.

P2, N=1376, Active, not recruiting, National Cancer Institute (NCI) | Trial completion date: May 2026 --> Jan 2027

P3, N=94, Recruiting, Tata Memorial Centre

These findings support the concept that conventional histology can capture relevant heterogeneity and may complement molecular studies. The recognition of such features may help refine histopathological assessment and provide practical prognostic insights, particularly in resource-limited settings where molecular testing is not universally available.

Pediatric ependymomas are not uniformly immune-silent. ZFTA-RELA and recurrent tumors exhibit a "primed but suppressed" immune phenotype, where the immune machinery is present but functionally restrained, suggesting greater susceptibility to ICB, whereas PF-A tumors remain immune-excluded and may require microenvironmental modulation to achieve immunotherapy benefit.

P1, N=12, Active, not recruiting, University of Florida | Recruiting --> Active, not recruiting