Biopolym. Cell. 2006; 22(1):38-48.
Molecular Biomedicine
Overexpression of genes at different stages of astrocytic glioma development
1Dmytrenko V. V., 1Boyko O. I., 1Shostak K. O., 1Symyrenko O. E., 1Bukreyeva T. V., 2Rozumenko V. D., 2Malysheva T. A., 2Shamaev M. I., 2Zozulya Y. P., 1Kavsan V. M.
  1. Institute of Molecular Biology and Genetics, NAS of Ukraine
    150, Akademika Zabolotnoho Str., Kyiv, Ukraine, 03680
  2. Institute of Neurosurgery named after A. P. Romodanov, NAMS of Ukraine
    32, Manuilskogo Str., Kyiv, Ukraine, 04050

Abstract

Public database of Serial Analysis of Gene Expression (SAGE) was used for identification of potential human astrocytic glioma molecular markers. The comparison of nine glioblastoma SAGE-libraries, eleven anaplastic astrocytoma SAGE-libraries, eight diffusive astrocytoma SAGE-libraries, and five human normal brain SAGE-libraries revealed 57 genes with more than 5-fold increase of expression in astrocytic gliomas (P≤0.05) comparing to the human normal brain. Besides the genes expression changes which occur at the early stage of astrocytomas formations and are revealed also during the subsequent stages of progression, some changes are characteristic only of highly malignant stages of tumor development while they are absent in the tumors of low stage of malignancy. The analysis of revealed genes expression can be used for glial tumor molecular classification, diagnosis, prognostic evaluation and determination of potential targets for anticancer therapy.
Keywords: SAGE, differential expression, astrocytic glioma, molecular markers

References

[1] Kleihues P, Louis DN, Scheithauer BW, Rorke LB, Reifenberger G, Burger PC, Cavenee WK. The WHO classification of tumors of the nervous system. J Neuropathol Exp Neurol. 2002;61(3):215-25; discussion 226-9.
[2] Watanabe T, Nakamura M, Kros JM, Burkhard C, Yonekawa Y, Kleihues P, Ohgaki H. Phenotype versus genotype correlation in oligodendrogliomas and low-grade diffuse astrocytomas. Acta Neuropathol. 2002;103(3):267-75.
[3] Okamoto Y, Di Patre PL, Burkhard C, Horstmann S, Jourde B, Fahey M, Schüler D, Probst-Hensch NM, Yasargil MG, Yonekawa Y, Lütolf UM, Kleihues P, Ohgaki H. Population-based study on incidence, survival rates, and genetic alterations of low-grade diffuse astrocytomas and oligodendrogliomas. Acta Neuropathol. 2004;108(1):49-56.
[4] Negm RS, Verma M, Srivastava S. The promise of biomarkers in cancer screening and detection. Trends Mol Med. 2002;8(6):288-93.
[5] Huang H, Okamoto Y, Yokoo H, Heppner FL, Vital A, Fevre-Montange M, Jouvet A, Yonekawa Y, Lazaridis EN, Kleihues P, Ohgaki H. Gene expression profiling and subgroup identification of oligodendrogliomas. Oncogene. 2004;23(35):6012-22.
[6] Shai R, Shi T, Kremen TJ, Horvath S, Liau LM, Cloughesy TF, Mischel PS, Nelson SF. Gene expression profiling identifies molecular subtypes of gliomas. Oncogene. 2003;22(31):4918-23.
[7] Shostak K, Labunskyy V, Dmitrenko V, Malisheva T, Shamayev M, Rozumenko V, Zozulya Y, Zehetner G, Kavsan V. HC gp-39 gene is upregulated in glioblastomas. Cancer Lett. 2003;198(2):203-10.
[8] Dmitrenko V, Shostak K, Boyko O, Khomenko O, Rozumenko V, Malisheva T, Shamayev M, Zozulya Y, Kavsan V. Reduction of the transcription level of the mitochondrial genome in human glioblastoma. Cancer Lett. 2005;218(1):99-107.
[9] Kavsan V, Shostak K, Dmitrenko V, Chausovskiy T, Zozulya Y, Demotes-Mainard J. Peculiarities of molecular events in human glial tumors revealed by serial analysis of gene expression (SAGE). Exp Oncol. 2004;26(3):196-204.
[10] Loging WT, Lal A, Siu IM, Loney TL, Wikstrand CJ, Marra MA, Prange C, Bigner DD, Strausberg RL, Riggins GJ. Identifying potential tumor markers and antigens by database mining and rapid expression screening. Genome Res. 2000;10(9):1393-402.
[11] Ljubimova JY, Lakhter AJ, Loksh A, Yong WH, Riedinger MS, Miner JH, Sorokin LM, Ljubimov AV, Black KL. Overexpression of alpha4 chain-containing laminins in human glial tumors identified by gene microarray analysis. Cancer Res. 2001;61(14):5601-10.
[12] Cheng Y, Ng HK, Ding M, Zhang SF, Pang JC, Lo KW. Molecular analysis of microdissected de novo glioblastomas and paired astrocytic tumors. J Neuropathol Exp Neurol. 1999;58(2):120-8.
[13] Zhang L, Zhou W, Velculescu VE, Kern SE, Hruban RH, Hamilton SR, Vogelstein B, Kinzler KW. Gene expression profiles in normal and cancer cells. Science. 1997;276(5316):1268-72.