Aka:
- Alpha-thalassemia/mental retardation syndrome
General
- Nondeletion type
- X-Iinked
- ATRX protein is part of the SWI/SNF2 (SWItch/Sucrose Non Fermentable) family of chromatin remodelling proteins,
Function
- Combine with DAXX (death domain associated protein), a transcription cofactor to maintains genomic stability through its deposition of the replication-independent histone variant H3.3 at telomeres and pericentromeric heterochromatin
- There is a correlation between ATRX mutations and Alternative Lengthening of Telomeres (ALT), a non-telomerase-dependent telomere lengthening mechanism
Disease
- ATRX loss
- Diffuse hemispheric glioma, H3 G34-mutant
- Astrocytoma, IDH-mutant (has both loss and mutation)
- In gliomas has been demonstrated to promote ALT
- ATRX deficiency has been shown to impair non-homologous end joining (NHEJ), which may explain increased cellular sensitivity to DNA-damaging agents that induce double-strand DNA breaks
- ATRX gene mutations
- High-grade astrocytoma with piloid features (HGAP)
- Astrocytoma, IDH-mutant (has both loss and mutation)
- Are strongly coupled to IDH & TP53 mutations
- Secondary GBM and its precursors (grade Il & grade Ill gliomas)
- ATRX mutations confer a better progression free and overall survival in low grade glioma harboring IDH mutations without 1p/19q co-deletion
- Uncommon in oligodendrogliomas and secondary GBMs
- ATRX Retained
Presence in tumour
- ATRX is rarely mutated in glioblastoma, but it is more common in younger adult patients with lower grade gliomas
- With respect to glioblastoma, ATRX expression is varied.
- Lower ATRX expression has been observed more commonly in primary GBM and anaplastic gliomas relative to grade II gliomas, implicating its status as a marker of malignancy
Test
- PCR and IHC stains
- Easy reliable test
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