PATH-78. First Reported Case of MALAT1-GLI Fusion in a Spinal Cord Astrocytoma

BACKGROUND Spinal cord anaplastic astrocytoma is a rare (incidence 0.4%) CNS tumor with limited molecular characterization compared to intracranial counterparts. While fusions involving GLI family genes have been implicated in other tumor types (Gastroblastoma, Plexiform Fibromyxoma, Malignant Epithelioid Neoplasm with GLI1 fusions), MALAT1-GLI fusions have not previously been reported in spinal gliomas. MALAT1 (Metastasis Associated Lung Adenocarcinoma Transcript 1) is a long non-coding RNA frequently involved in oncogenic rearrangements. We describe the first known case of a MALAT1-GLI fusion in a spinal cord astrocytoma, offering novel insight into the molecular landscape of these tumors. CASE A 43-year-old male presented with progressive lower extremity weakness and numbness. MRI revealed an intramedullary spinal cord lesion extending from C7 to T2. Subtotal resection was performed and revealed a cellular neoplasm with increased mitotic activity and partially compact architecture. The findings were consistent with anaplastic astrocytoma, WHO grade 3. He underwent concurrent radiation therapy and temozolomide and then needed a second surgery for the placement of a shunt due to syrinx. Abnormal tissue was resampled, but only a few atypical cells consistent with residual astrocytoma were observed. He has remained in observation for 8 years without progression. To identify a potential IDH mutation, comprehensive genomic profiling was performed. Surprisingly, a MALAT1-GLI fusion was identified. No other pathogenic mutations or fusions were identified. DISCUSSION The identification of a MALAT1-GLI fusion in a spinal cord astrocytoma is not previously described. The fusion likely results in constitutive activation of GLI1, driving oncogenesis via aberrant Hedgehog pathway signaling. While anaplastic astrocytoma is often associated with a prognosis of 5 years, this patient has survived 8 years at the time of submission. In other cases, there was an association with long term survival. This molecular alteration may represent a novel therapeutic target, should there be recurrence, and given the prolonged progression free survival, it may represent a prognostic marker.