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Disease Markers
Volume 2015 (2015), Article ID 241301, 13 pages
http://dx.doi.org/10.1155/2015/241301
Research Article

Identification of Novel Epigenetic Markers of Prostate Cancer by NotI-Microarray Analysis

1Engelhardt Institute of Molecular Biology, Russian Academy of Sciences, Moscow 119991, Russia
2P.A. Herzen Moscow Cancer Research Institute, Ministry of Healthcare of the Russian Federation, Moscow 125284, Russia
3Institute of Molecular Biology and Genetics, National Academy of Sciences of Ukraine, Kiev 03680, Ukraine
4Department of Microbiology, Tumor and Cell Biology, Karolinska Institute, 17177 Stockholm, Sweden
5Institute of Urology, National Academy of Medical Sciences of Ukraine, Kiev 04053, Ukraine
6Department of Molecular Biology, Kurchatov NBIC Centre NRC “Kurchatov Institute”, Moscow 123182, Russia
7Bioinformatics Infrastructure for Life Sciences, Science for Life Laboratory, Karolinska Institute, 17177 Stockholm, Sweden

Received 9 February 2015; Revised 11 July 2015; Accepted 14 July 2015

Academic Editor: Stamatios Theocharis

Copyright © 2015 Alexey A. Dmitriev et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

A significant need for reliable and accurate cancer diagnostics and prognosis compels the search for novel biomarkers that would be able to discriminate between indolent and aggressive tumors at the early stages of disease. The aim of this work was identification of potential diagnostic biomarkers for characterization of different types of prostate tumors. NotI-microarrays with 180 clones associated with chromosome 3 genes/loci were applied to determine genetic and epigenetic alterations in 33 prostate tumors. For 88 clones, aberrations were detected in more than 10% of tumors. The major types of alterations were DNA methylation and/or deletions. Frequent methylation of the discovered loci was confirmed by bisulfite sequencing on selective sampling of genes: FGF12, GATA2, and LMCD1. Three genes (BHLHE40, BCL6, and ITGA9) were tested for expression level alterations using qPCR, and downregulation associated with hypermethylation was shown in the majority of tumors. Based on these data, we proposed the set of potential biomarkers for detection of prostate cancer and discrimination between prostate tumors with different malignancy and aggressiveness: BHLHE40, FOXP1, LOC285205, ITGA9, CTDSPL, FGF12, LOC440944/SETD5, VHL, CLCN2, OSBPL10/ZNF860, LMCD1, FAM19A4, CAND2, MAP4, KY, and LRRC58. Moreover, we probabilistically estimated putative functional relations between the genes within each set using the network enrichment analysis.