GENO-08
NEXT GENERATION SEQUENCING REVEALS DISTINCT PROGNOSTIC CLASSES AMONG GRADE II/III GLIOMAS Free

BACKGROUND: WHO grade II and III gliomas are heterogeneous both genotypically and phenotypically. Genomic characterization and prognostic classification of grade II and III gliomas has only recently begun to be elucidated. Therefore, we retrospectively analyzed an institutional cohort of grade II/III gliomas (n = 62). METHODS: A custom Ion Torrent next generation sequencing panel was used to sequence IDH1, IDH2, CIC, FUBP1, and ATRX. TERT promoter mutations were analyzed by Sanger sequencing. 1p/19q co-deletion status was determined by the Illumina 450K Array and the Affymetrix Oncoscan platform (in select cases). Each marker was analyzed for prognostic significance by logrank tests and multivariate (MVA) Cox regression analysis. RESULTS: The cohort consisted of 22 grade II and 40 grade III tumors. IDH1/2 mutations were found in 87% (54/62), ATRX mutations in 24% (15/62), CIC/FUBP1 mutations in 39% (24/62), and TERT mutations in 52% (27/52) of the cases. 1p/19q co-deletions were found in 51% (31/61) of the cases. Regarding classification of 1p/19q co-deletion, four cases were discordant between FISH compared to the 450K array or Oncoscan likely due to high heterogeneity in these cases and more information gained with high-density platforms. In the logrank tests, 1p/19q co-deletion (HR 2.0; p = 0.019) and IDH1/2 mutations (HR = 8.7; p < 0.001) were associated with better PFS. IDH1/2 mutations (p < 0.001), CIC/FUBP1 mutations (p = 0.021), and 1p/19q co-deletion (p < 0.001) were found to be significantly correlated with OS. In MVA, IDH mutation and 1p/19q co-deletion were independent prognostic factors for both OS and PFS after adjustment for age and grade. Three prognostic groups were also examined (IDHwt, IDHmut/non-co-del, and IDHmut/co-del) and were found to be significantly associated (p < 0.05) with PFS and OS upon MVA. CONCLUSIONS: Our findings confirm the favorable prognostic information of IDH mutations and 1p/19q co-deletion independent of grade in gliomas. The predictive value of these molecular alterations remains to be determined.