| First Author | Koschmann C | Year | 2016 |
| Journal | Sci Transl Med | Volume | 8 |
| Issue | 328 | Pages | 328ra28 |
| PubMed ID | 26936505 | Mgi Jnum | J:247300 |
| Mgi Id | MGI:5922286 | Doi | 10.1126/scitranslmed.aac8228 |
| Citation | Koschmann C, et al. (2016) ATRX loss promotes tumor growth and impairs nonhomologous end joining DNA repair in glioma. Sci Transl Med 8(328):328ra28 |
| abstractText | Recent work in human glioblastoma (GBM) has documented recurrent mutations in the histone chaperone protein ATRX. We developed an animal model of ATRX-deficient GBM and showed that loss of ATRX reduces median survival and increases genetic instability. Further, analysis of genome-wide data for human gliomas showed that ATRX mutation is associated with increased mutation rate at the single-nucleotide variant (SNV) level. In mouse tumors, ATRX deficiency impairs nonhomologous end joining and increases sensitivity to DNA-damaging agents that induce double-stranded DNA breaks. We propose that ATRX loss results in a genetically unstable tumor, which is more aggressive when left untreated but is more responsive to double-stranded DNA-damaging agents, resulting in improved overall survival. |
