EPEN-41. C11orf95-RELA FUSION REGULATES ABERRANT GENE EXPRESSION THROUGH THE UNIQUE GENOMIC BINDING SITES FOR EPENDYMOMA FORMATION. (4th December 2020)

• Record Type: Journal Article
• Authors: Ozawa, Tatsuya; Kaneko, Syuzo; Takadera, Mutsumi; Holland, Eric; Hamamoto, Ryuji; Ichimura, Koichi
• Is Part Of: Neuro-oncology. Volume 22(2020)Supplement 3
• Page Start: iii316
• Page End: iii316
• Publication Date: 2020-12-04
• Subjects: Brain Neoplasms -- Periodicals; Brain -- Tumors -- Periodicals; Brain -- Cancer -- Periodicals; Nervous system -- Cancer -- Periodicals; 616.99481
• DOI: 10.1093/neuonc/noaa222.175
• Languages: English
• ISSNs: 1522-8517

Abstract

Abstract: A majority of supratentorial ependymoma is associated with recurrent C11orf95-RELA fusion (RELA FUS ). The presence of RELA as one component of the RELA FUS leads to the suggestion that NF-kB activity is involved in the ependymoma formation, thus being a viable therapeutic target in these tumors. However, the oncogenic role of another C11orf95 component in the tumorigenesis is not still determined. In this study, to clarify the molecular mechanism underlying tumorigenesis of RELA FUS, we performed RELA FUS -ChIP-Seq analysis in cultured cells expressing the RELA FUS protein. Genomic profiling of RELA FUS binding sites pinpointed the transcriptional target genes directly regulated by RELA FUS . We then identified a unique DNA binding motif of the RELA FUS different from the canonical NF-kB motif in de novo motif discovery analysis. Significant responsiveness of RELA FUS but not RELA to the motif was confirmed in the reporter assay. An N-terminal portion of C11orf95 was sufficient to localize in the nucleus and recognizes the unique motif. Interestingly, the RELA FUS peaks concomitant with the unique motif were identified around the transcription start site in the RELA FUS target genes as previously reported. These observations suggested that C11orf95 might have served as a key determinant for the DNA binding sites of RELA FUS, thereby induced aberrant gene expression necessary for ependymoma formation. Our results will give insights into the development of new ependymoma therapy.