@article{d5d3323bd9124169bfdfbc424db1f7c7,
title = "Loss of ATM/Chk2/p53 Pathway Components Accelerates Tumor Development and Contributes to Radiation Resistance in Gliomas",
abstract = "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.",
author = "Massimo Squatrito and Brennan, {Cameron W.} and Karim Helmy and Huse, {Jason T.} and Petrini, {John H.} and Holland, {Eric C.}",
note = "Funding Information: We thank Robert Finney, Quancho Zhang, and Eletha Carbajal for technical support. We thank Diane Domingo for the flow cytometric analysis. We thank members of Holland lab for discussion. We gratefully acknowledge the TCGA Consortium for providing samples, tissues, and data processing and making data and results available. The results published here are in part based upon data generated by The Cancer Genome Atlas pilot project established by the NCI and NHGRI. Information about TCGA and the investigators and institutions who constitute the TCGA research network can be found at http://cancergenome.nih.gov . This work was supported by the Fondazione Italiana Ricerca Cancro and American Brain Tumor Association Research Fellowship in memory of Justin Porter (to M.S.), and a National Brain Tumor Society Grant Award (to E.C.H.). J.H.P. is supported by NIH grants. K.H. is a Howard Hughes Medical Institute Medical Research Training Fellow. ",
year = "2010",
month = dec,
day = "14",
doi = "10.1016/j.ccr.2010.10.034",
language = "English (US)",
volume = "18",
pages = "619--629",
journal = "Cancer cell",
issn = "1535-6108",
publisher = "Cell Press",
number = "6",
}