DNAR-01. CHROMOTHRIPSIS, ONE MAJOR GENETIC INSTABILITY FACTOR IN GLIOBLASTOMA, IS RARE IN IDH-MUTANT GLIOMAS. (14th November 2022) - Sourty, Baptiste
Abstract: INTRODUCTION: Adult-type diffuse gliomas comprise IDH -mutant astrocytomas, IDH -mutant 1p/19q codeleted oligodendrogliomas, and IDH -wildtype glioblastomas (GBM). GBM display genomic instability, which is favored by two genetic events leading to massive chromosomal alterations: chromothripsis (CT) and whole-genome duplication (WGD). Those events are scarcely described in IDH -mutant gliomas. The better prognosis of IDH -mutant gliomas may be in part related to their greater genomic stability compared to GBM. METHODS: Pangenomic profiles of 301 adult diffuse gliomas were analyzed at initial diagnosis by SNP arrays, including 196 GBM and 105 IDH -mutant gliomas (61 astrocytomas and 44 oligodendrogliomas). We further analyzed 16 IDH -mutant recurrent gliomas (11 astrocytomas and 5 oligodendrogliomas). Tumor ploidy was assessed with Genome Alteration Print and CT events with CTLPScanner and through manual screening. Survival data were compared using Kaplan-Meier method and categorical variables using Chi 2 test. RESULTS: At initial diagnosis, 37 GBM (18.8%) displayed CT (mainly affecting chromosomes 12, 9 and 7) versus five IDH -mutant gliomas (4.8%) (p = 0.0007). The latter were all high-grade astrocytomas. No oligodendroglioma or grade 2 astrocytoma displayed CT. There was a trend towards higher occurrence of CT in GBM versus high-grade IDH -mutant astrocytomas (p = 0.0589). WGD was detected at initial diagnosis in 18 GBM (9.2%) and 9 IDH -mutant gliomas (of any subtype and grade; 8.6%). Over 75% of chromosomal losses occurred after WGD. Neither CT nor WGD was associated with overall survival in GBM. At recurrence, one grade 4 IDH -mutant astrocytoma displayed CT and another one, WGD with CT. CONCLUSION: CT is rare in IDH -mutant gliomas compared to GBM. The absence of CT in oligodendrogliomas and grade 2 astrocytomas may contribute to their greater genomic stability and better prognosis. CT occurrence in high-grade IDH -mutant astrocytomas may underlie aggressive biological behavior. WGD is a rare early event occurring equally in IDH -mutant gliomas and GBM.