ATRX mutations and glioblastoma: Impaired DNA damage repair, alternative lengthening of telomeres, and genetic instability

Carl Koschmann; Pedro R Lowenstein; Maria G Castro

doi:10.1080/23723556.2016.1167158

ATRX mutations and glioblastoma: Impaired DNA damage repair, alternative lengthening of telomeres, and genetic instability

Mol Cell Oncol. 2016 Apr 27;3(3):e1167158. doi: 10.1080/23723556.2016.1167158. eCollection 2016 May.

Authors

Carl Koschmann¹, Pedro R Lowenstein², Maria G Castro²

Affiliations

¹ 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.
² Department of Neurosurgery and Department of Cell and Developmental Biology, University of Michigan School of Medicine , Ann Arbor, MI, USA.

Abstract

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).

Keywords: Chromatin; NHEJ; histone mutations; homologous recombination; pediatric GBM.

Abstract

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