DIPG-27. GLIAL TUMOURS IN CHILDREN AND YOUNG ADULTS: ISOLATED ATRX ALTERATIONS, DO THEY REPRESENT DISTINCT SUBGROUP?

INTRODUCTION: This study is correlation of ATRX-loss with histone and IDH-mutations in astrocytic tumours of children and young adults. MATERIALS AND METHODS: Study sample included: 1. High-grade (HGA) and all non-pilocytic astrocytomas, non-BRAF altered low-grade glial tumours (LGANOS) in ≤39 years, 2. EGFR non-amplified/IDH1/2 wild type midline located HGA with loss of ATRX in 40–55 years. ATRX by immunohistochemistry, H3.3, H3.1 and IDH1R132/IDH2R172 mutations by Sanger sequencing was done. RESULTS: Total cases: 365[1st group: 356 (HGA: 346; LGANOS: 10); 2nd group: 9]. 133 (37.4%), 54 (15.2%) and 51 (14.3%) of 1st group showed IDH-mutations, histone-alterations and isolated ATRX-loss respectively. Of the 2nd group, 2 and 3 cases showed histone-alterations and isolated ATRX-loss respectively. Overall 56 were histone gene-altered - H3.3 (K27M=41, K27E=2, G34R=8, G34V=1), H3.1 (HIST3BK27M=3) and frameshift mutation (n=1). Age-range of H3K27M/K27E (n=46): 1–46 years (0–3: 3, 4–6:2, 7–14: 16, 15–18:5, 19–25:8, 26–30:4, 31–39:6, >39: 2) and G34R/G34V: 7–26 years (7–14:4, 15–18:3, 19–25:1, 26–30:1). 11(24%) K27-mutant and 1 (11%) of G34-mutant were of superficial cerebral hemispheric (SCH) location. Four K27M-mutant were low-grade. 28 histone-altered cases [52%; K27M: 19 (43.2%), G34R/V:8 (89%), Frameshift:1] showed ATRX-loss. Interestingly, 54 (14.8%) cases showed isolated ATRX-loss with age-range 4–43 years (4–6:2, 7–14:11, 15–18:2, 19–25:13, 26–30:11, 31–39:12, >39:3). All were high-grade; 4 were midline while the rest were SCH. CONCLUSIONS: Isolated ATRX-loss, a distinct alteration in HGA of children and young adults. H3K27-mutations can be seen in adults; G34-mutations can be seen in young children and rarely both can be uncommon variants (K27E, G34V).