Prognostic implications of the DNA damage response pathway in glioblastoma

  • Authors:
    • Ho Jun Seol
    • Hae Yong Yoo
    • Juyoun Jin
    • Kyeung Min Joo
    • Doo-Sik Kong
    • Su Jin Yoon
    • Heekyoung Yang
    • Wonyoung Kang
    • Do-Hoon Lim
    • Kwan Park
    • Jong Hyun Kim
    • Jung-II Lee
    • Do-Hyun Nam
  • View Affiliations

  • Published online on: May 26, 2011     https://doi.org/10.3892/or.2011.1325
  • Pages: 423-430
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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.

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August 2011
Volume 26 Issue 2

Print ISSN: 1021-335X
Online ISSN:1791-2431

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Spandidos Publications style
Seol HJ, Yoo HY, Jin J, Joo KM, Kong D, Yoon SJ, Yang H, Kang W, Lim D, Park K, Park K, et al: Prognostic implications of the DNA damage response pathway in glioblastoma. Oncol Rep 26: 423-430, 2011
APA
Seol, H.J., Yoo, H.Y., Jin, J., Joo, K.M., Kong, D., Yoon, S.J. ... Nam, D. (2011). Prognostic implications of the DNA damage response pathway in glioblastoma. Oncology Reports, 26, 423-430. https://doi.org/10.3892/or.2011.1325
MLA
Seol, H. J., Yoo, H. Y., Jin, J., Joo, K. M., Kong, D., Yoon, S. J., Yang, H., Kang, W., Lim, D., Park, K., Kim, J. H., Lee, J., Nam, D."Prognostic implications of the DNA damage response pathway in glioblastoma". Oncology Reports 26.2 (2011): 423-430.
Chicago
Seol, H. J., Yoo, H. Y., Jin, J., Joo, K. M., Kong, D., Yoon, S. J., Yang, H., Kang, W., Lim, D., Park, K., Kim, J. H., Lee, J., Nam, D."Prognostic implications of the DNA damage response pathway in glioblastoma". Oncology Reports 26, no. 2 (2011): 423-430. https://doi.org/10.3892/or.2011.1325