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- Dmitriev, AA, et al.
(författare)
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Epigenetic alterations of chromosome 3 revealed by NotI-microarrays in clear cell renal cell carcinoma
- 2014
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Ingår i: BioMed research international. - : Hindawi Limited. - 2314-6141 .- 2314-6133. ; 2014, s. 735292-
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Tidskriftsartikel (refereegranskat)abstract
- This study aimed to clarify epigenetic and genetic alterations that occur during renal carcinogenesis. The original method includes chromosome 3 specific NotI-microarrays containing 180 NotI-clones associated with 188 genes for hybridization with 23 paired normal/tumor DNA samples of primary clear cell renal cell carcinomas (ccRCC). Twenty-two genes showed methylation and/or deletion in 17–57% of tumors. These genes include tumor suppressors or candidates (VHL, CTDSPL, LRRC3B, ALDH1L1, andEPHB1) and genes that were not previously considered as cancer-associated (e.g.,LRRN1, GORASP1, FGD5, andPLCL2). Bisulfite sequencing analysis confirmed methylation as a frequent event in ccRCC. A set of six markers (NKIRAS1/RPL15, LRRN1, LRRC3B, CTDSPL, GORASP1/TTC21A, andVHL) was suggested for ccRCC detection in renal biopsies. The mRNA level decrease was shown for 6 NotI-associated genes in ccRCC using quantitative PCR:LRRN1, GORASP1, FOXP1, FGD5, PLCL2,andALDH1L1. The majority of examined genes showed distinct expression profiles in ccRCC and papillary RCC. The strongest extent and frequency of downregulation were shown forALDH1L1gene both in ccRCC and papillary RCC. Moreover, the extent ofALDH1L1mRNA level decrease was more pronounced in both histological types of RCC stage III compared with stages I and II (P=0.03). The same was observed forFGD5gene in ccRCC (P<0.06).
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| 2. |
- Dmitriev, AA, et al.
(författare)
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Identification of Novel Epigenetic Markers of Prostate Cancer by NotI-Microarray Analysis
- 2015
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Ingår i: Disease markers. - : Hindawi Limited. - 1875-8630 .- 0278-0240. ; 2015, s. 241301-
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Tidskriftsartikel (refereegranskat)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, andLMCD1. Three genes (BHLHE40,BCL6, andITGA9) 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, andLRRC58. Moreover, we probabilistically estimated putative functional relations between the genes within each set using the network enrichment analysis.
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