MPTH-30ATRX CAN OCCUR IN IDH WILD-TYPE GBM

Abstract

BACKGROUND: ATRX (alpha thalassemia/ mental retardation syndrome X-linked) is a transcriptional regulatory protein which contains an ATPase/helicase domain. In gliomas loss of ATRX expression has been recently described and is mostly restricted to IDH mutant tumors who seem to have a significantly better prognosis. ATRX loss is thought to be extremely rare in IDH wild type (WT) tumors and in that setting one group reported H3F3A mutation. METHODS: Tissue samples of 23 patients with IDH wild-type malignant gliomas were analyzed for ATRX expression using immunohistochemistry. ATRX status was associated with clinical characteristics, histology and other molecular markers (MGMT, BRAF, EGFR). RESULTS: Median age in all patients was 49,3 years. Loss of ATRX expression was detected in 4 out of 23 patient tumors. All ATRX loss patients were primary glioblastomas. Median survival in ATRX mutated gliomas is 237 weeks which was longer than overall survival in gliomas with retained ATRX (88 weeks). All of our patients underwent concurrent chemoradiotherapy with temozolomide. One out of four ATRX loss tumors was BRAF mutated, three out of four ATRX loss patients tested for EGFR were found to be wild type and the two ATRX mutated patients tested for MGMT were methylated. CONCLUSION: ATRX mutation can occur in IDH wild-type patients. In that setting it appears to be associated with a better outcome. Our data is hypothesis generating. Tumors with IDH WT/ ATRX loss should be evaluated prospectively in a larger cohort and possibly checked for H3F3A mutation.