期刊
CANCER CELL
卷 18, 期 6, 页码 619-629出版社
CELL PRESS
DOI: 10.1016/j.ccr.2010.10.034
关键词
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资金
- Fondazione Italiana Ricerca Cancro
- American Brain Tumor Association
- National Brain Tumor Society
- NIH
- Associazione Italiana per la Ricerca sul Cancro Funding Source: Custom
Maintenance of genomic integrity is essential for adult tissue homeostasis and defects in the DNA-damage response (DDR) machinery are linked to numerous pathologies including cancer. Here, we present evidence that the DDR exerts tumor suppressor activity in gliomas. We show that genes encoding components of the DDR pathway are frequently altered in human gliomas and that loss of elements of the ATM/Chk2/p53 cascade accelerates tumor formation in a glioma mouse model. We demonstrate that Chk2 is required for glioma response to ionizing radiation in vivo and is necessary for DNA-damage checkpoints in the neuronal stem cell compartment. Finally, we observed that the DDR is constitutively activated in a subset of human GBMs, and such activation correlates with regions of hypoxia.
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