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 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.
Engelhardt Institute of Molecular Biology, Russian Academy of Sciences, Moscow 119991, Russia ; P.A. Herzen Moscow Cancer Research Institute, Ministry of Healthcare of the Russian Federation, Moscow 125284, Russia.
Alexey A
AA
Dmitriev
Institute of Molecular Biology and Genetics, National Academy of Sciences of Ukraine, Kiev 03680, Ukraine.
Eugenia E
EE
Rosenberg
Engelhardt Institute of Molecular Biology, Russian Academy of Sciences, Moscow 119991, Russia.
George S
GS
Krasnov
Institute of Molecular Biology and Genetics, National Academy of Sciences of Ukraine, Kiev 03680, Ukraine.
Ganna V
GV
Gerashchenko
Institute of Molecular Biology and Genetics, National Academy of Sciences of Ukraine, Kiev 03680, Ukraine.
Vasily V
VV
Gordiyuk
Department of Microbiology, Tumor and Cell Biology, Karolinska Institute, 17177 Stockholm, Sweden.
Tatiana V
TV
Pavlova
Engelhardt Institute of Molecular Biology, Russian Academy of Sciences, Moscow 119991, Russia.
Anna V
AV
Kudryavtseva
Engelhardt Institute of Molecular Biology, Russian Academy of Sciences, Moscow 119991, Russia.
Artemy D
AD
Beniaminov
Engelhardt Institute of Molecular Biology, Russian Academy of Sciences, Moscow 119991, Russia.
Anastasia A
AA
Belova
Institute of Urology, National Academy of Medical Sciences of Ukraine, Kiev 04053, Ukraine.
Yuriy N
YN
Bondarenko
Institute of Urology, National Academy of Medical Sciences of Ukraine, Kiev 04053, Ukraine.
Rostislav O
RO
Danilets
Department of Molecular Biology, Kurchatov NBIC Centre NRC "Kurchatov Institute", Moscow 123182, Russia.
Alexander I
AI
Glukhov
Institute of Molecular Biology and Genetics, National Academy of Sciences of Ukraine, Kiev 03680, Ukraine.
Aleksandr G
AG
Kondratov
Bioinformatics Infrastructure for Life Sciences, Science for Life Laboratory, Karolinska Institute, 17177 Stockholm, Sweden.
Andrey
A
Alexeyenko
P.A. Herzen Moscow Cancer Research Institute, Ministry of Healthcare of the Russian Federation, Moscow 125284, Russia.
Boris Y
BY
Alekseev
Department of Microbiology, Tumor and Cell Biology, Karolinska Institute, 17177 Stockholm, Sweden.
George
G
Klein
Engelhardt Institute of Molecular Biology, Russian Academy of Sciences, Moscow 119991, Russia.
Vera N
VN
Senchenko
Institute of Molecular Biology and Genetics, National Academy of Sciences of Ukraine, Kiev 03680, Ukraine ; Department of Microbiology, Tumor and Cell Biology, Karolinska Institute, 17177 Stockholm, Sweden.
Vladimir I
VI
Kashuba
D014408:Biomarkers, Tumor / Q000235:genetics*; D016022:Case-Control Studies; D019175:DNA Methylation; D044127:Epigenesis, Genetic; D017353:Gene Deletion; D053263:Gene Regulatory Networks; D006801:Humans; D008297:Male; D020411:Oligonucleotide Array Sequence Analysis; D011471:Prostatic Neoplasms / Q000235:genetics* / Q000473:pathology
D014408:Biomarkers, Tumor