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• Kashuba, V
• Dmitriev, A
• Krasnov, G
• Pavlova, T
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• Gerashchenko, A
• Braga, E
• Yenamandra, S
• Lerman, M
• Senchenko, V
• Zabarovsky, E
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• Kashuba, V
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• Krasnov, G
• Pavlova, T
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• Gerashchenko, A
• Braga, E
• Yenamandra, S
• Lerman, M
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• Zabarovsky, E
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Int. J. Mol. Sci. 2012, 13(10), 13352-13377; doi:10.3390/ijms131013352

Article

NotI Microarrays: Novel Epigenetic Markers for Early Detection and Prognosis of High Grade Serous Ovarian Cancer

Vladimir Kashuba ^1,2,† , Alexey A. Dmitriev ^3,† , George S. Krasnov ³ , Tatiana Pavlova ¹ , Ilya Ignatjev ¹ , Vasily V. Gordiyuk ² , Anna V. Gerashchenko ² , Eleonora A. Braga ⁴ , Surya P. Yenamandra ¹ , Michael Lerman ⁵ , Vera N. Senchenko ³  and Eugene Zabarovsky ^1,3,6,*

¹ Department of Microbiology, Tumor and Cell Biology, Karolinska Institute, Stockholm SE-171 77, Sweden ² Department of Molecular Oncogenetics, Institute of Molecular Biology and Genetics, NASU, Kiev 01000, Ukraine ³ Laboratory of Structural and Functional Genomics, Engelhard Institute of Molecular Biology, Russian Academy of Science, Moscow 119991, Russia ⁴ Russian State Genetics Center GosNIIgenetika, Moscow 117545, Russia ⁵ Affina Biotechnologies, Stamford, CT 06902, USA ⁶ Linköping University, Department of Clinical and Experimental Medicine, Linköping SE-581 85, Sweden ^† These authors contributed equally to this work.

* Author to whom correspondence should be addressed.

Received: 10 August 2012; in revised form: 12 September 2012 / Accepted: 12 September 2012 / Published: 18 October 2012

(This article belongs to the Special Issue Cancer Molecules in Ovarian Cancer 2012)

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Abstract: Chromosome 3-specific NotI microarray (NMA) containing 180 clones with 188 genes was used in the study to analyze 18 high grade serous ovarian cancer (HGSOC) samples and 7 benign ovarian tumors. We aimed to find novel methylation-dependent biomarkers for early detection and prognosis of HGSOC. Thirty five NotI markers showed frequency of methylation/deletion more or equal to 17%. To check the results of NMA hybridizations several samples for four genes (LRRC3B, THRB, ITGA9 and RBSP3 (CTDSPL)) were bisulfite sequenced and confirmed the results of NMA hybridization. A set of eight biomarkers: NKIRAS1/RPL15, THRB, RBPS3 (CTDSPL), IQSEC1, NBEAL2, ZIC4, LOC285205 and FOXP1, was identified as the most prominent set capable to detect both early and late stages of ovarian cancer. Sensitivity of this set is equal to (72 ± 11)% and specificity (94 ± 5)%. Early stages represented the most complicated cases for detection. To distinguish between Stages I + II and Stages III + IV of ovarian cancer the most perspective set of biomarkers would include LOC285205, CGGBP1, EPHB1 and NKIRAS1/RPL15. The sensitivity of the set is equal to (80 ± 13)% and the specificity is (88 ± 12)%. Using this technique we plan to validate this panel with new epithelial ovarian cancer samples and add markers from other chromosomes.

Keywords: ovarian cancer; biomarkers; NotI microarrays; epigenetics; early detection of ovarian cancer; prognosis of ovarian cancer

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