P04.01 * RELA FUSION DEFINES CLINICOPATHOLOGIC SUBSETS OF SUPRATENTORIAL EPENDYMOMA: A STUDY FROM THE COLLABORATIVE EPENDYMOMA RESEARCH NETWORK

Abstract

A novel fusion involving C11ORF95 and RelA was recently described in supratentorial ependymomas. We sought to further characterize the clinical relevance of this fusion. We evaluated a cohort of 98 supratentorial ependymomas from the collaborative ependymoma research network (CERN) tissue repository. Screening of fusion transcripts from FFPE-derived RNA for the 2 most common fusion breakpoints (representing over 90% of cases when a fusion is present), we found 30 fusion-positive cases and 68 cases in which either fusion transcript was not present. With a goal of comparing fusion-positive vs. fusion negative cases, we found that fusion positive-cases were most likely to be diagnosed as anaplastic-grade III compared to fusion-negative cases (67% vs. 41%, respectively). The median patient age of fusion-positive cases was younger than fusion-negative cases (9.5 vs. 24.7 years). Overall, 20/52 (38%) of pediatric cases (age <21), were fusion-positive, compared with 10/46 (22%) of adult cases. Patient outcomes (overall- and progression-free survival) were not significantly different between fusion-positive and fusion-negative cases. Thirty-six of the 98 cases included in this study were examined for changes in DNA copy number (using Oncoscan, performed by Affymetrix) showing that patterns of copy number changes differed based on fusion status: losses in 9p, 11q and 14q and gains of 16q were significantly more common in fusion- positive cases. Conversely gains in 12, 18q and 20p were more common in fusion-negative cases: for example, loss of 9p was found in 38% of fusion-positive cases but only 6% of fusion-negative cases; conversely gain of 12q was not found in fusion-positive cases but was present in 30% of fusion-negative cases. Overall, this study extends the findings of the RelA fusion in supratentorial ependymoma by showing that it is nearly twice as common in pediatric cases, tends to present more frequently as WHO grade III and exhibits distinct patterns of DNA copy number aberration. These results identify clinical, pathologic and molecular correlates of RelA fusion status and extends the findings originally reported to robustly to define 2 major molecular subgroups of supratentorial ependymoma.