Cross-species genomics reveals oncogenic dependencies in ZFTA/C11orf95 fusion-positive supratentorial ependymomas.

摘要: Molecular groups of supratentorial ependymomas comprise tumors with ZFTA-RELA or YAP1-involving fusions and fusion-negative subependymoma. However, occasionally cannot be readily assigned to any these due lack detection a typical fusion and/or ambiguous DNA methylation-based classification. An unbiased approach cohort unprecedented size revealed distinct methylation clusters composed ependymal but also various other histological features containing alternative translocations that shared ZFTA as partner gene. Somatic overexpression ZFTA-associated genes in the developing cerebral cortex is capable inducing tumor formation vivo, cross-species comparative analyses identified GLI2 key downstream regulator tumorigenesis all tumors. Targeting arsenic trioxide caused extended survival tumor-bearing animals, indicating potential therapeutic vulnerability fusion-positive