ATRX mutations and glioblastoma: Impaired DNA damage repair, alternative lengthening of telomeres, and genetic instability.
Alpha thalassemia/mental retardation syndrome X-linked (ATRX) is mutated in nearly a third of pediatric glioblastoma (GBM) patients. We developed an animal model of ATRX-deficient GBM. Using this model combined with analysis of multiple human glioma genome-wide datasets, we determined that ATRX mutation leads to genetic instability, impaired non-homologous end joining, and alternate lengthening of telomeres (ALT).
Department of Pediatrics, Division of Pediatric Hematology-Oncology, University of Michigan School of Medicine, Ann Arbor, MI, USA; Department of Neurosurgery and Department of Cell and Developmental Biology, University of Michigan School of Medicine, Ann Arbor, MI, USA.
Carl
C
Koschmann
Department of Neurosurgery and Department of Cell and Developmental Biology, University of Michigan School of Medicine , Ann Arbor, MI, USA.
Pedro R
PR
Lowenstein
Department of Neurosurgery and Department of Cell and Developmental Biology, University of Michigan School of Medicine , Ann Arbor, MI, USA.
Maria G
MG
Castro
Chromatin; NHEJ; histone mutations; homologous recombination; pediatric GBM