4.4 Article

Expression analyses of 27 DNA repair genes in astrocytoma by TaqMan low-density array

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NEUROSCIENCE LETTERS
卷 409, 期 2, 页码 112-117

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ELSEVIER IRELAND LTD
DOI: 10.1016/j.neulet.2006.09.038

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astrocytoma; DNA repair; low-density array : real-time PCR

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DNA repair systems act to maintain genome integrity in the face of replication errors, environmental insults, and the cumulative effects of age. The mRNA expressions of 27 genes of the DNA repair system as well as their correlation with the clinical characteristics were studied in human astrocytoma. We applied TaqMan low-density array to investigate the mRNA expressions of 27 DNA repair genes in 40 astrocytoma tissues (10 of grade II, 10 of grade III, and 20 of grade IV, according to the WHO Grading System). And the normal brain tissues front 10 non-astrocytoma patients were collected as the control. In addition, correlation of their mRNA levels with clinical characteristics was also analyzed. We found that the expression of the 13 genes were significantly (P < 0.01) down-regulated in grade II, III, IV of astrocytoma compared to normal brain tissues, including ERCC 1, ERCC2, ERCC3, ERCC4, MGMT, MLH1, MLH3, NTHL1, OGG1, RAD50, SMUG 1, XRCC4 and XRCC5. Meanwhile, we found that the expression of MSH2, MSH6, NUDT1 and XRCC3 were only significantly lower in grade 11 and III of astrocytoma, and the expression of MRE11A and MUS81 were only significantly lower in grade III and IV. But the expression of MPG, MSH3, MUTHY and RAD51 were not changed in any grade of astrocytoma. Furthermore, we found that the decrease expression of eight genes was significantly (P < 0.05) associated with a poor prognosis, including ERCC3, ERCC4, MLH3, MRE1A, NTHL1, RAD50, XRCC4 and XRCC5. We suggest that TaqMan low-density array is an effective multivariate technique to examine the expression of DNA repair genes in astrocytomas, which can be applied to identify tumor-specific genes. We also suggest that the down-regulation of some DNA repair genes may be associated with pathogenesis and poor prognosis of astrocytoma. (c) 2006 Elsevier Ireland Ltd. All rights reserved.

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