Identification of Novel Epigenetic Markers of Prostate Cancer by NotI-Microarray Analysis
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 f...
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doaj-7b1427a5dd6245bdb8bdce3751d0a1b32020-11-24T23:58:50ZengHindawi LimitedDisease Markers0278-02401875-86302015-01-01201510.1155/2015/241301241301Identification of Novel Epigenetic Markers of Prostate Cancer by NotI-Microarray AnalysisAlexey A. Dmitriev0Eugenia E. Rosenberg1George S. Krasnov2Ganna V. Gerashchenko3Vasily V. Gordiyuk4Tatiana V. Pavlova5Anna V. Kudryavtseva6Artemy D. Beniaminov7Anastasia A. Belova8Yuriy N. Bondarenko9Rostislav O. Danilets10Alexander I. Glukhov11Aleksandr G. Kondratov12Andrey Alexeyenko13Boris Y. Alekseev14George Klein15Vera N. Senchenko16Vladimir I. Kashuba17Engelhardt Institute of Molecular Biology, Russian Academy of Sciences, Moscow 119991, RussiaInstitute of Molecular Biology and Genetics, National Academy of Sciences of Ukraine, Kiev 03680, UkraineEngelhardt Institute of Molecular Biology, Russian Academy of Sciences, Moscow 119991, RussiaInstitute of Molecular Biology and Genetics, National Academy of Sciences of Ukraine, Kiev 03680, UkraineInstitute of Molecular Biology and Genetics, National Academy of Sciences of Ukraine, Kiev 03680, UkraineDepartment of Microbiology, Tumor and Cell Biology, Karolinska Institute, 17177 Stockholm, SwedenEngelhardt Institute of Molecular Biology, Russian Academy of Sciences, Moscow 119991, RussiaEngelhardt Institute of Molecular Biology, Russian Academy of Sciences, Moscow 119991, RussiaEngelhardt Institute of Molecular Biology, Russian Academy of Sciences, Moscow 119991, RussiaInstitute of Urology, National Academy of Medical Sciences of Ukraine, Kiev 04053, UkraineInstitute of Urology, National Academy of Medical Sciences of Ukraine, Kiev 04053, UkraineDepartment of Molecular Biology, Kurchatov NBIC Centre NRC “Kurchatov Institute”, Moscow 123182, RussiaInstitute of Molecular Biology and Genetics, National Academy of Sciences of Ukraine, Kiev 03680, UkraineBioinformatics Infrastructure for Life Sciences, Science for Life Laboratory, Karolinska Institute, 17177 Stockholm, SwedenP.A. Herzen Moscow Cancer Research Institute, Ministry of Healthcare of the Russian Federation, Moscow 125284, RussiaDepartment of Microbiology, Tumor and Cell Biology, Karolinska Institute, 17177 Stockholm, SwedenEngelhardt Institute of Molecular Biology, Russian Academy of Sciences, Moscow 119991, RussiaInstitute of Molecular Biology and Genetics, National Academy of Sciences of Ukraine, Kiev 03680, UkraineA 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.http://dx.doi.org/10.1155/2015/241301 |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Alexey A. Dmitriev Eugenia E. Rosenberg George S. Krasnov Ganna V. Gerashchenko Vasily V. Gordiyuk Tatiana V. Pavlova Anna V. Kudryavtseva Artemy D. Beniaminov Anastasia A. Belova Yuriy N. Bondarenko Rostislav O. Danilets Alexander I. Glukhov Aleksandr G. Kondratov Andrey Alexeyenko Boris Y. Alekseev George Klein Vera N. Senchenko Vladimir I. Kashuba |
spellingShingle |
Alexey A. Dmitriev Eugenia E. Rosenberg George S. Krasnov Ganna V. Gerashchenko Vasily V. Gordiyuk Tatiana V. Pavlova Anna V. Kudryavtseva Artemy D. Beniaminov Anastasia A. Belova Yuriy N. Bondarenko Rostislav O. Danilets Alexander I. Glukhov Aleksandr G. Kondratov Andrey Alexeyenko Boris Y. Alekseev George Klein Vera N. Senchenko Vladimir I. Kashuba Identification of Novel Epigenetic Markers of Prostate Cancer by NotI-Microarray Analysis Disease Markers |
author_facet |
Alexey A. Dmitriev Eugenia E. Rosenberg George S. Krasnov Ganna V. Gerashchenko Vasily V. Gordiyuk Tatiana V. Pavlova Anna V. Kudryavtseva Artemy D. Beniaminov Anastasia A. Belova Yuriy N. Bondarenko Rostislav O. Danilets Alexander I. Glukhov Aleksandr G. Kondratov Andrey Alexeyenko Boris Y. Alekseev George Klein Vera N. Senchenko Vladimir I. Kashuba |
author_sort |
Alexey A. Dmitriev |
title |
Identification of Novel Epigenetic Markers of Prostate Cancer by NotI-Microarray Analysis |
title_short |
Identification of Novel Epigenetic Markers of Prostate Cancer by NotI-Microarray Analysis |
title_full |
Identification of Novel Epigenetic Markers of Prostate Cancer by NotI-Microarray Analysis |
title_fullStr |
Identification of Novel Epigenetic Markers of Prostate Cancer by NotI-Microarray Analysis |
title_full_unstemmed |
Identification of Novel Epigenetic Markers of Prostate Cancer by NotI-Microarray Analysis |
title_sort |
identification of novel epigenetic markers of prostate cancer by noti-microarray analysis |
publisher |
Hindawi Limited |
series |
Disease Markers |
issn |
0278-0240 1875-8630 |
publishDate |
2015-01-01 |
description |
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. |
url |
http://dx.doi.org/10.1155/2015/241301 |
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