ATRX plays a role in chromatin regulation and maintenance of telomeres. It regulates incorporation of histone H3.3 into telomeric chromatin (1). ATRX is also a major component of various essential cellular pathways such as DNA replication and repair, chromatin higher-order structure regulation, gene transcriptional regulation, etc. (2) ATRX loss was observed in grades II/III astrocytomas, oligoastrocytomas, oligodendrogliomas, and glioblastomas. In grades II/III gliomas, most ATRX‐ loss cases had IDH1/2 mutations (3). ATRX mutations accompanied by an alternative lengthening of telomeres (ALT), impacted favorable survival of patients with astrocytic tumors (4). Assessment of ATRX loss by immunohistochemical staining captures the majority of mutations, indicating that the use of immunohistochemical testing in routine neuropathology diagnostics gives a reasonable sensitivity (5). ATRX mutation is also detected in neuroblastoma, osteosarcoma, and pancreatic neuro-endocrine tumors (6).
1. Lu HC, et al. Aberrant ATRX protein expression is associated with poor overall survival in NF1-MPNST. Oncotarget. 2018 May; 9:23018-28.
2. Haase S, et al. Mutant ATRX: uncovering a new therapeutic target for glioma. Expert Opin Ther Targets. 2018 Jul;22(7):599-613.
3. Ikemura M, et al. Utility of ATRX immunohistochemistry in diagnosis of adult diffuse gliomas. Histopathology. 2016 Aug;69(2):260-7.
4. Cai J, et al. Detection of ATRX and IDH1-R132H immunohistochemistry in the progression of 211 paired gliomas. Oncotarget. 2016 Mar;7(13):16384- 95.
5. Cai J, et al. ATRX, IDH1-R132H and Ki-67 immunohistochemistry as a classification scheme for astrocytic tumors. Oncoscience. 2016 Sep ;3(7- 8):258-65.
6. Koschmann C, et al. ATRX loss promotes tumor growth and impairs nonhomologous end joining DNA repair in glioma. Sci Transl Med. 2016 Mar;8(328):328ra28.
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8. Clinical and Laboratory Standards Institute (CLSI). Protection of Laboratory Workers from Occupationally Acquired Infections; Approved Guideline-Fourth Edition CLSI document M29-A4 Wayne, PA 2014.