title: Prognostic implications of the DNA damage response pathway in glioblastoma.
abstract: Genomic instability and resistance to genotoxic therapies for glioblastoma (GBM) suggest aberrant DNA damage response (DDR), since DDR maintains the genomic integrity against genotoxic insults including anti-tumor therapies. To elucidate the biological and clinical meaning of DDR in GBM, we retrospectively investigated the immunohistochemical expression of DDR proteins (ATM, Chk1, Chk2, TopBP1, Rad17, p53, Nbs1, MDC1, γH2AX and RPA1) in 69 GBM surgical samples and their relation with GBM patient survival. Remarkably, higher expression of ATM revealed significantly longer overall survival (OS) and progression-free survival (PFS) (p<0.05). Upon multivariate analysis, expression level of ATM was an independent factor for longer OS (p=0.020) and longer PFS (p=0.019). Since ATM induces cell cycle arrest or apoptosis through cell cycle regulators in response to genotoxic insults, these results indicate that aberrant DDR signaling through ATM in GBM may be associated with resistance to genotoxic anti-tumor therapeutics. Conclusively, we emphasize that the identification of DDR machinery, which can be involved in unstable genomic status or genotoxic therapies in GBM, is very important to predict patient outcome.
authors: Department of Neurosurgery, Samsung Medical Center, Sungkyunkwan University School of Medicine, 50 Ilwon-Dong, Gangnam-Gu, Seoul 135-710, Republic of Korea.
authors: Ho Jun
authors: HJ
authors: Seol
authors: Hae Yong
authors: HY
authors: Yoo
authors: Juyoun
authors: J
authors: Jin
authors: Kyeung Min
authors: KM
authors: Joo
authors: Doo-Sik
authors: DS
authors: Kong
authors: Su Jin
authors: SJ
authors: Yoon
authors: Heekyoung
authors: H
authors: Yang
authors: Wonyoung
authors: W
authors: Kang
authors: Do-Hoon
authors: DH
authors: Lim
authors: Kwan
authors: K
authors: Park
authors: Jong Hyun
authors: JH
authors: Kim
authors: Jung-Ii
authors: JI
authors: Lee
authors: Do-Hyun
authors: DH
authors: Nam