ATRX alterations are strongly associated with the presence of the alternative lengthening of telomeres (ALT) phenotype, and within the central nervous system they tend to occur in subsets of gliomas, including those with IDH, NF1, or histone (H3 K27M or G34) mutations.
ATRX loss induces multiple hallmarks of the alternative lengthening of telomeres (ALT) phenotype in human glioma cell lines in a cell line-specific manner.
These include the alternative lengthening of telomeres (ALT) phenotype associated with mutations in the ATRX and DAXX genes and recurrent point mutations in the TERT gene promoter.
Forced resolution of sister telomere cohesion induces excessive recombination between non-homologs, genomic instability, and impaired cell growth, indicating the ATRX-macroH2A1.1-tankyrase axis as a potential therapeutic target in ALT tumors.