Abstract LB-80: ATRX loss refines the classification of anaplastic glioma and is a favorable prognostic marker.

Abstract

Mutation / loss of ATRX expression has been described in anaplastic gliomas. The present study explored the role for ATRX status in the molecular classification of anaplastic gliomas and the impact of ATRX status on survival in the biomarker cohort of the NOA-04 trial. Patients (n=123) of the NOA-04 trial were analyzed for ATRX expression using immunohistochemistry. ATRX status was correlated with age, reference histology, IDH, 1p/19q and MGMT status, and the efficacy endpoints of the NOA-04 trial. Loss of ATRX expression was detected in 42% of anaplastic astrocytomas, 24% of anaplastic oligoastrocytomas and 10% of anaplastic oligodendrogliomas. It was restricted to IDH mutated tumors and almost mutually exclusive with 1p/19q co-deletion. Anaplastic oligoastrocytoma harboring ATRX loss shared a similar clinical course with anaplastic astrocytoma. Survival analysis showed a separation of IDH mutant tumors into two groups based on ATRX status: Tumors with ATRX loss have a significantly better prognosis (median time to treatment failure 1758 days [95% CI 1316 days - to not reached] vs. 968 days [95% CI 496 days - to not reached], log rank test, p = 0.0044). Independent of histological subtype, patients whose tumors harbored ATRX loss had a longer overall survival when initially treated with radiotherapy rather than with chemotherapy (p = 0.03). ATRX status helps to re-classify oligoastrocytomas, since ATRX loss is a hallmark of astrocytic tumors. Furthermore, ATRX loss defines a subgroup of tumors with a favorable prognosis and predicts benefit from radiotherapy. Citation Format: Benedikt Wiestler, David Capper, Tim Holland-Letz, Andreas von Deimling, Stefan M. Pfister, Michael Platten, Michael Weller, Wolfgang Wick. ATRX loss refines the classification of anaplastic glioma and is a favorable prognostic marker. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr LB-80. doi:10.1158/1538-7445.AM2013-LB-80

Low Protein Expression of both ATRX and ZNRF3 as Novel Negative Prognostic Markers of Adult Adrenocortical Carcinoma

“…ATRX is suggested to be a suppressor of the ALT pathway [ 47 ]. Cohorts of different malignancies have shown that ATRX alterations have prognostic value [ 54 , 55 , 56 , 57 , 58 , 59 , 60 , 61 , 62 , 63 , 64 , 65 ].…”