Detection of methylation in the CpG islands of the RASSF1A and RAR2b gene promoters in breast cancer (BC)

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. e14632-e14632
Author(s):  
K. Desiris ◽  
S. Voyatzi ◽  
P. Stravoravdi ◽  
I. Boukovinas ◽  
A. Kiziridou ◽  
...  
Keyword(s):  
Retinoic Acid Receptor ◽  
Cpg Islands ◽  
Clinicopathological Features ◽  
Epigenetic Mechanism ◽  
Aberrant Methylation ◽  
Gene Promoters ◽  
Benign Lesions ◽  
Rassf1a Gene ◽  
Specific Pcr ◽  
Er Status

e14632 Background: Aberrant methylation of CpG islands of cancer-related genes has emerged as an important epigenetic mechanism during carcinogenesis. We examined the methylation of RASSF1A (Ras-association domain family 1, isoform A) and RAR2b (Retinoic Acid Receptor 2b) genes in BC. The knowledge of their role in BC is limited and confused to date. Methods: Promoter methylation was measured in 37 pts, 26 with BC and 11 with benign lesions. The specimens were obtained from archive formalin-fixed paraffin-embedded tumors. After DNA extraction, the methylation was determined by chemical modification of DNA with sodium bisulfite and subsequent double “hot start” Methylation-Specific PCR (MSP), followed by detection on agarose gel. Results: Methylation of at least one of the genes was observed in 18/26 pts (p<0.05). Methylation of RASSF1A gene was observed in 15/26 and RAR2b in 11/26 pts. Both genes were methylated in 8/26 pts. Correlation between methylation and clinicopathological features revealed an association of the RASSF1A gene with T2 tumors (12/15 pts, p<0.05) and ER (+) status (12/15 pts, p<0.05). T2 tumors and ER (+) status presented together in 9/15 pts. The methylation of RAR2b gene was not associated with any known clinicopathological features. In benign lesions methylation of at least one of the genes was observed in 8/11 pts (p<0.05). Methylation of RASSF1A gene was observed in 5/11 pts and RAR2b in 7/11 pts. Both genes were methylated in 4/11 pts. Conclusions: Both genes are frequently methylated in both benign and malignant breast lesions. The association of methylation of RASSF1A gene with tumor size and ER status is noteworthy. The small number of pts does not allow us to confirm the exact role of gene methylation in BC yet. Larger studies are required in order to assess if these epigenetic alterations point out new BC markers, which could be helpful for BC control. No significant financial relationships to disclose.

Do age-related changes in DNA methylation play a role in the development of age-related diseases?

2013 ◽  
Vol 41 (3) ◽  
pp. 803-807 ◽  
Author(s):  
Sanne D. van Otterdijk ◽  
John C. Mathers ◽  
Gordon Strathdee
Keyword(s):  
Gene Expression ◽  
Dna Methylation ◽  
Cpg Islands ◽  
Large Body ◽  
Epigenetic Mechanism ◽  
Aberrant Methylation ◽  
Gene Promoters ◽  
Cpg Sites ◽  
Pathological Conditions ◽  
Age Related

DNA methylation is an important epigenetic mechanism in mammalian cells. It occurs almost exclusively at CpG sites and has a key role in a number of biological processes. It plays an important part in regulating chromatin structure and has been best studied for its role in controlling gene expression. In particular, hypermethylation of gene promoters which have high levels of CpG sites, known as CpG islands, leads to gene inactivation. In healthy cells, however, it appears that only a small number of genes are controlled through promoter hypermethylation, such as genes on the inactivated X-chromosome or at imprinted loci, and most promoter-associated CpG islands remain methylation-free regardless of gene expression status. However, a large body of evidence has now shown that this protection from methylation not only breaks down in a number of pathological conditions (e.g. cancer), but also already occurs during the normal process of aging. The present review focuses on the methylation changes that occur during healthy aging and during disease development, and the potential links between them. We focus especially on the extent to which the acquisition of aberrant methylation changes during aging could underlie the development of a number of important age-related pathological conditions.

scholarly journals Influence of DAT1 Promotor Methylation on Sports Performance

Genes ◽  
2021 ◽  
Vol 12 (9) ◽  
pp. 1425
Author(s):  
Anna Grzywacz ◽  
Krzysztof Chmielowiec ◽  
Agnieszka Boroń ◽  
Monika Michałowska-Sawczyn ◽  
Jolanta Chmielowiec ◽  
...  
Keyword(s):  
Dna Methylation ◽  
Cpg Islands ◽  
Epigenetic Mechanism ◽  
Control Group ◽  
Sports Performance ◽  
European Origin ◽  
Specific Pcr ◽  
Dat1 Gene ◽  
Male Subjects

In the mammalian genome, DNA methylation is an epigenetic mechanism involving the transfer of a methyl group onto the C5 position of the cytosine to form 5-methylcytosine. DNA methylation regulates gene expression by recruiting proteins involved in gene repression or by inhibiting the binding of transcription factors (TFs) to DNA. As there are still many questions concerning the role of methylation in creating personality, we concentrated on searching for such associations. The research group was 100 sports male subjects (mean age = 22.88, SD = 6.35), whereas the control group included 239 healthy male volunteers matched for age (mean age = 21.69, SD = 3.39), both of European origin. The methods used in our research were as follows: DNA isolation, methylation-specific PCR, sequencing chromatophores, all conducted according to the manufacturer’s procedure. To evaluate personality traits, the NEO Five-Factor Personality Inventory (NEO-FFI) and STAI Inventory were used. We observed the existence of a statistically significant correlation for all the aspects of personality covered and CpG islands’ methylation. Nonetheless, we think that the tested group and the number of tested promotor islands in the DAT1 gene are still too small to make explicit conclusions, so it needs further profound analysis.

scholarly journals HYPERMETHYLATED DNA AS BIOMARKER FOR NASOPHARYNGEAL CANCER DETECTION

2018 ◽  
Vol 11 (9) ◽  
pp. 68
Author(s):  
Thuan Duc Lao ◽  
Thuy Ai Huyen Le
Keyword(s):  
Southern China ◽  
Cpg Islands ◽  
Nasopharyngeal Cancer ◽  
Pyrimidine Ring ◽  
Epigenetic Mechanism ◽  
Epstein Barr Virus Infection ◽  
Aberrant Methylation ◽  
Environmental Carcinogens ◽  
Dna Hypermethylation ◽  
Potential Biomarker

Backgroud: Nasopharyngeal carcinoma (NPC) is a malignancy with remarkable geographic and distribution worldwide, toward in Southern China and Southern Asia. In addition to Epstein–Barr virus infection, environmental carcinogens, the development of NPC involves the cumulative genetic as well as epigenetic alteration. More recently, it has been reported that DNA hypermethylation, an epigenetic mechanism, that occurred by the addition of a methyl group at 5’ position of the pyrimidine ring of cytosine residues at CpG islands, has been considered as the cause of nasopharyngeal tumorigenesis. In recent years, many reports have focused on the identification, evaluation of aberrant methylation of target tumor suppressor genes’ promoters, such as RASSF1A, BLU, DLEC, RARβ, p16, p15, p14, and MGMT in the NPC development.Objective: We focused on the description and exemplification of the DNA hypermethylation changes in nasopharyngeal carcinoma.Conclusion: we highlighted the DNA hypermethylation as a potential biomarker applied in monitoring, screening, and early diagnosis for cancer of nasopharynx.

scholarly journals ChIP-seq Profiling Identifies Histone Deacetylase 2 Targeting Genes Involved in Immune and Inflammatory Regulation Induced by Calcitonin Gene-Related Peptide in Microglial Cells

2020 ◽  
Vol 2020 ◽  
pp. 1-10
Author(s):  
Xingjing Guo ◽  
Dan Chen ◽  
Shuhong An ◽  
Zhaojin Wang
Keyword(s):  
Signaling Pathway ◽  
Histone Deacetylase ◽  
Calcitonin Gene Related Peptide ◽  
Epigenetic Mechanism ◽  
Microglial Cells ◽  
Transcriptional Level ◽  
Gene Promoters ◽  
Histone Deacetylase 2 ◽  
Related Peptide ◽  
Calcitonin Gene

Calcitonin gene-related peptide (CGRP) is a mediator of microglial activation at the transcriptional level. The involvement of the epigenetic mechanism in this process is largely undefined. Histone deacetylase (HDAC)1/2 are considered important epigenetic regulators of gene expression in activated microglia. In this study, we examined the effect of CGRP on HDAC2-mediated gene transcription in microglial cells through the chromatin immunoprecipitation sequencing (ChIP-seq) method. Immunofluorescence analysis showed that mouse microglial cells (BV2) expressed CGRP receptor components. Treatment of microglia with CGRP increased HDAC2 protein expression. ChIP-seq data indicated that CGRP remarkably altered promoter enrichments of HDAC2 in microglial cells. We identified 1271 gene promoters, whose HDAC2 enrichments are significantly altered in microglia after CGRP treatment, including 1181 upregulating genes and 90 downregulating genes. Bioinformatics analyses showed that HDAC2-enriched genes were mainly associated with immune- and inflammation-related pathways, such as nitric oxide synthase (NOS) biosynthetic process, retinoic acid-inducible gene- (RIG-) like receptor signaling pathway, and nuclear factor kappa B (NF-κB) signaling pathway. The expression of these key pathways (NOS, RIG-I, and NF-κB) were further verified by Western blot. Taken together, our findings suggest that genes with differential HDAC2 enrichments induced by CGRP function in diverse cellular pathways and many are involved in immune and inflammatory responses.

Aberrant methylation of CpG islands in intraductal papillary mucinous neoplasms of the pancreas

2002 ◽  
Vol 123 (1) ◽  
pp. 365-372 ◽  
Author(s):  
Norihiro Sato ◽  
Takashi Ueki ◽  
Noriyoshi Fukushima ◽  
Christine A. Iacobuzio–Donahue ◽  
Ralph H. Hruban ◽  
...  
Keyword(s):  
Cpg Islands ◽  
Aberrant Methylation ◽  
Intraductal Papillary Mucinous Neoplasms ◽  
Mucinous Neoplasms

Aberrant Genes Promoter Methylation in Neural Crest-Derived Tumors

2012 ◽  
Vol 27 (4) ◽  
pp. 389-394 ◽  
Author(s):  
Annamaria La Torre ◽  
Lucia Anna Muscarella ◽  
Paola Parrella ◽  
Teresa Balsamo ◽  
Michele Bisceglia ◽  
...  
Keyword(s):  
Small Bowel ◽  
Neural Crest ◽  
Promoter Methylation ◽  
Methylation Status ◽  
Cpg Islands ◽  
Aberrant Methylation ◽  
Tumor Type ◽  
Epigenetic Landscape ◽  
Molecular Biomarker

Disturbances in the epigenetic landscape by aberrant methylation of CpG islands can lead to inactivation of cancer-related genes in solid tumors. We analyzed the promoter methylation status of 6 genes previously reported as cancer-specific methylated (MCAM, SSBP2, NISCH, B4GALT1, KIF1A and RASSF1A) in 38 neural crest-derived tumors by quantitative methylation-specific real-time PCR (QMSP). The results demonstrated that the determination of the methylation status of RASSF1A is able to distinguish between normal and tumor samples in cutaneous melanomas, lung carcinoids and small bowel carcinoids. MCAM methylation levels were significantly higher in lung carcinoids tumors (p=0.001), suggesting that this alteration may represent a molecular biomarker in this tumor type.

scholarly journals Suppression of canonical TGF-β signaling enables GATA4 to interact with H3K27me3 demethylase JMJD3 to promote cardiomyogenesis

2020 ◽  
Author(s):  
Andrew S. Riching ◽  
Etienne Danis ◽  
Yuanbiao Zhao ◽  
Yingqiong Cao ◽  
Congwu Chi ◽  
...  
Keyword(s):  
Transforming Growth Factor Beta ◽  
Target Genes ◽  
Transforming Growth Factor ◽  
Epigenetic Mechanism ◽  
Gene Promoters ◽  
Pathway Activation ◽  
Cardiac Gene ◽  
Growth Factor Beta ◽  
Heart Injury ◽  
Cardiac Transcription Factors

SummaryDirect reprogramming of fibroblasts into cardiomyocytes (CMs) represents a promising strategy to regenerate CMs lost after ischemic heart injury. Overexpression of GATA4, HAND2, MEF2C, TBX5, miR-1, and miR-133 (GHMT2m) along with transforming growth factor beta (TGF-β) inhibition efficiently promotes reprogramming. However, the mechanisms by which TGF-β blockade promotes cardiac reprogramming remain unknown. Here, we identify interactions between the histone H3 lysine 27 trimethylation (H3K27me3) – demethylase JMJD3, the SWI/SNF remodeling complex subunit BRG1, and cardiac transcription factors. Furthermore, canonical TGF-β signaling regulates the interaction between GATA4 and JMJD3. TGF-β activation impairs the ability of GATA4 to bind target genes and prevents demethylation of H3K27 at cardiac gene promoters during cardiac reprogramming. Finally, a mutation in GATA4 (V267M) exhibits reduced binding to JMJD3 and impaired cardiomyogenesis. Thus, we have identified an epigenetic mechanism wherein canonical TGF-β pathway activation impairs cardiac gene programming by interfering with GATA4-JMJD3 interactions.

scholarly journals Landscape Of HOXA Genes Methylation in Colorectal Cancer

2020 ◽  
Vol 3 (1) ◽  
Author(s):  
Muhiddin Ishak ◽  
Rashidah Baharudin ◽  
Loh Teng-Hern Tan ◽  
Learn-Han Lee ◽  
Nurul-Syakima Ab Mutalib
Keyword(s):  
Colorectal Cancer ◽  
Cancer Susceptibility ◽  
Cpg Islands ◽  
Methylation Pattern ◽  
Gene Promoters ◽  
Normal Tissues ◽  
Genes Encoding ◽  
Hoxa Genes ◽  
A Minor ◽  
Hoxa Gene

Colorectal cancer (CRC) is among the most common cancers worldwide and the second leading cause of cancer-related death in Malaysia. The HOXA gene cluster is a family of Homeobox A genes encoding transcriptional regulators that play vital roles in cancer susceptibility and progression. Dysregulated HOXA expression influences various aspects of carcinogenesis processes. Therefore, this study aims to elucidate the methylation landscape of HOXA genes in CRC. Twelve pairs of CRC — adjacent normal tissues were subjected to Infinium DNA MethyEPIC array. Differentially methylatedregions were identified using the ChAMP Bioconductor and methylation levels of HOXA genes were manually curated. We identified 100 significantly differentially methylated probes annotated to HOXA genes. HOXA3 has the highest number of differentially methylated probes (n=27), followed by HOXA2 (n=20) and HOXA4 (n=14). The majority (43%) of the probes were located at the transcription start site (TSS) 200, which is one of the gene promoters. In respect to CpG islands (CGI), the probes were equally located in the island and shore regions (47% each) while a minor percentage was in the shelf (6%). Our work gave a comprehensive assessment of the DNA methylation pattern of HOXA genes and provide the first evidence of HOXA2, HOXA3 and HOXA4 differential methylation in Malaysian CRC. The new knowledge from this study can be utilized to further increase our understanding of CRC methylomics, particularly on the homeobox A genes. The prognostic and diagnostic roles of the differentially methylated HOXA genes warrant future investigations.

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