BI-30 * CHARACTERIZATION OF L1CAM AS A CLINICAL MARKER FOR THE C11orf95-RELA FUSION IN SUPRATENTORIAL EPENDYMOMAS

Abstract

BACKGROUND: Recently, a novel oncogenic fusion involving C11orf95 and RELA genes was described in a subset of supratentorial ependymoma causing aberrant activation of the NF-κB pathway. METHODS: We evaluated a cohort of 83 supratentorial ependymomas from the CERN tissue repository using RNAseq, RT-PCR and Illumina 450k profiling. RESULTS: RNAseq expression profiling identified L1CAM, a neuronal cell adhesion protein, as the most differentially expressed gene between fusion-positive and fusion-negative cases, with a 200 fold higher expression in the fusion-positive subgroup. Testing for the 2 most common fusion types showed positivity in 29/83 cases for an aberrant transcript and L1CAM IHC showed a concordance between IHC and fusion transcript status (positive IHC/fusion positive and negative IHC/fusion-negative) in 58/83 cases. Since prior work has shown a relationship between global methylation profile and fusion status, genome-wide DNA methylation (Illumina, 450K) was performed on a subset of 71 of the 83 cases and of these 38/71 showed methylation profiles consistent with the presence of a fusion-positive tumor. Concordance of predicted fusion with L1CAM IHC was very high, with 66/71 cases showing concordance of positive staining with predicted fusion and negative staining with absence of fusion. As a test case, we recently were made aware of a case of malignant sarcoma in a patient with a prior supratentorial ependymoma. L1CAM staining was positive, as was L1CAM IHC from the original ependymoma from the same patient, suggesting that the sarcoma-like recurrent tumor likely derived from the ependymoma. Sanger sequencing of the DNA from both the tumors confirmed the presence of the fusion, indicating potential utility of the L1CAM IHC marker. CONCLUSION: This study provides preliminary evidence for the use of L1CAM as a surrogate marker for the presence of the C11orf95-RELA fusion in supratentorial ependymoma that can be considered in a clinical diagnostic lab setting.