EPIGENETIC ALTERATIONS ASSOCIATED WITH PREMATURE OVARIAN FAILURE

2008 ◽  
Vol 31 (4) ◽  
pp. 11
Author(s):  
Manda Ghahremani ◽  
Courtney W Hannah ◽  
Maria Peneherrera ◽  
Karla L Bretherick ◽  
Margo R Fluker ◽  
...  
Keyword(s):  
Dna Methylation ◽  
Premature Ovarian Failure ◽  
Promoter Region ◽  
Gene Promoter ◽  
Ovarian Failure ◽  
P Value ◽  
Epigenetic Alterations ◽  
Methylation Array ◽  
Cpg Sites ◽  
Deficient Mice

Background/Purpose: Premature ovarian failure (POF) affects 1% of women with a largely idiopathic and poorly understood etiology. The objective of this study was to identify specific epigenetic alterations by measuring DNA methylation of gene regulatory regions in women with POF vs. controls. Methods: Blood samples were collected from idiopathic POFpatients (Amenorrhea for at least 3 months and 2 serum FSH levels of > 40mIU/ml obtained > 1 month apart prior to age 40) and control women (CW) (healthy pregnancy after age 37 with out a pregnancy loss). Genomic DNA was extracted from EDTA anticoagulated blood and bisulfite converted for analysis using the Illumina Golden Gate Methylation Panel which measures DNA methylation at 1506 CpG sites in the promoter regions of 807 genes in 10 POF and 12 CW. Candidate genes with altered epigenetic marks between POF and CW at a nominal P-value < 0.05 were identified using a t-testcomparison within the Illumina bead studio software. Genes of interest were further analyzed for quantitative methylation at specific CpG sites using pyrosequencing in 30 POF and 30 CW. Results: Comparison of DNA methylation profiles of our initial POF and CW groups identified several genes with statistically significanthyper- or hypo- methylation in the POF group (P < 0.05), including the Androgen Receptor (AR)promoter region, which was significantly hypermethylated. To further validate these results, DNA methylation of the AR gene promoter was quantified bypryosequencing in a larger group of POF and CW. Pyrosequencing further confirmed a significantly higher DNA methylation of the AR promoter region inPOF vs. CW (P=0.007). Conclusions: This is a novel study identifying epigenetic alterations in POF. The hypermethylation of the AR gene in POF patients may cause decreased level of the AR in these women. This is especially interesting given a recent report of induced POF in AR deficient mice^1. Specific epigenetic markers, as identified by DNA methylation array profiling in blood, may serve as useful biomarkers for POF and other fertility disorders. However, it will need to be determined if these methylation changes are present prior to diagnosis, or are a consequence of menopause itself. Reference: 1.Hiroko S. et al. Premature ovarian failure in androgenreceptor deficient mice. PNAS;103:224-9

scholarly journals DNA methylation of the KLK8 gene in depression symptomatology

2021 ◽  
Vol 13 (1) ◽  
Author(s):  
Anna Starnawska ◽  
Lina Bukowski ◽  
Ana Chernomorchenko ◽  
Betina Elfving ◽  
Heidi Kaastrup Müller ◽  
...  
Keyword(s):  
Dna Methylation ◽  
Promoter Region ◽  
Multiple Testing ◽  
Monozygotic Twins ◽  
Depression Symptoms ◽  
Methylation Array ◽  
Depression Diagnosis ◽  
Cpg Sites ◽  
Severity Of Depression ◽  
Depression Symptomatology

Abstract Background Depression is a common, complex, and debilitating mental disorder estimated to be under-diagnosed and insufficiently treated in society. Liability to depression is influenced by both genetic and environmental risk factors, which are both capable of impacting DNA methylation (DNAm). Accordingly, numerous studies have researched for DNAm signatures of this disorder. Recently, an epigenome-wide association study of monozygotic twins identified an association between DNAm status in the KLK8 (neuropsin) promoter region and severity of depression symptomatology. Methods In this study, we aimed to investigate: (i) if blood DNAm levels, quantified by pyrosequencing, at two CpG sites in the KLK8 promoter are associated with depression symptomatology and depression diagnosis in an independent clinical cohort and (ii) if KLK8 DNAm levels are associated with depression, postpartum depression, and depression symptomatology in four independent methylomic cohorts, with blood and brain DNAm quantified by either MBD-seq or 450 k methylation array. Results DNAm levels in KLK8 were not significantly different between depression cases and controls, and were not significantly associated with any of the depression symptomatology scores after correction for multiple testing (minimum p value for KLK8 CpG1 = 0.12 for ‘Depressed mood,’ and for CpG2 = 0.03 for ‘Loss of self-confidence with other people’). However, investigation of the link between KLK8 promoter DNAm levels and depression-related phenotypes collected from four methylomic cohorts identified significant association (p value < 0.05) between severity of depression symptomatology and blood DNAm levels at seven CpG sites. Conclusions Our findings suggest that variance in blood DNAm levels in KLK8 promoter region is associated with severity of depression symptoms, but not depression diagnosis.

scholarly journals EGFR DNA Methylation Correlates With EGFR Expression, Immune Cell Infiltration, and Overall Survival in Lung Adenocarcinoma

2021 ◽  
Vol 11 ◽  
Author(s):  
Zhanyu Xu ◽  
Fanglu Qin ◽  
Liqiang Yuan ◽  
Jiangbo Wei ◽  
Yu Sun ◽  
...  
Keyword(s):  
Dna Methylation ◽  
Protein Expression ◽  
Lung Adenocarcinoma ◽  
Methylation Level ◽  
Promoter Region ◽  
Body Region ◽  
Gene Body ◽  
Immune Infiltration ◽  
Cpg Sites ◽  
Gene Body Region

BackgroundThe epidermal growth factor receptor (EGFR) is a primary target of molecular targeted therapy for lung adenocarcinoma (LUAD). The mechanisms that lead to epigenetic abnormalities of EGFR in LUAD are still unclear. The purpose of our study was to evaluate the abnormal methylation of EGFR CpG sites as potential biomarkers for LUAD.MethodsTo assess the differentially methylation CpG sites of EGFR in LUAD, we used an integrative study of Illumina HumanMethylation450K and RNA-seq data from The Cancer Genome Atlas (TCGA). We evaluated and compared EGFR multiple-omics data to explore the role of CpG sites located in EGFR promoter regions and gene body regions and the association with transcripts, protein expression levels, mutations, and somatic copy number variation. We calculated the correlation coefficients between CpG sites of EGFR and immune infiltration fraction (by MCPcounter and ESTIMATE) and immune-related pathways in LUAD. Finally, we validated the differential methylation of clinically and prognostically relevant CpG sites using quantitative methylation-specific PCR (qMSP).ResultsWe found that the methylation level of many EGFR CpGs in the promoter region was negatively correlated with the transcription level, protein expression, and SCNV, while the methylation at the gene body region was positively correlated with these features. The methylation level of EGFR CpGs in the promoter region was positively correlated with the level of immune infiltration and IFN-γ signature, while the opposite was found for methylation of the gene body region. The qMSP results showed that cg02316066 had a high methylation level, while cg02166842 had a low methylation level in LUAD. There was a high degree of co-methylation between cg02316066 and cg03046247.ConclusionOur data indicate that EGFR is an epigenetic regulator in LUAD acting through DNA methylation. Our research provides a theoretical basis for the further detection of EGFR DNA methylation as a predictive biomarker for LUAD survival and immunotherapy.

Deficiency in Vitamin B12 and Ferritin Is Associated With Epigenetic Alterations in Cancer Patients  

2021 ◽  
Author(s):  
Khaled A. Elawdan ◽  
Sabah Farouk ◽  
Salah Araf ◽  
Hany Khalil
Keyword(s):  
Dna Methylation ◽  
Vitamin B12 ◽  
Cancer Patients ◽  
Promoter Region ◽  
Dna Methyltransferases ◽  
Epigenetic Alterations ◽  
Promoter Regions ◽  
Methylation Sensitive Restriction Enzyme ◽  
Low Levels ◽  
Dna Methylation Analysis

Abstract Background: Cancer is the second-leading cause of death worldwide, caused by several mutations in DNA within the cells including epigenetic alteration. The epigenetic changes are external modifications to the DNA that switch “on” or “off” gene expression. The present study was conducted to investigate the epigenetic modifications and its correlation with the levels of vitamin B12 and ferritin in cancer patients with hepatocellular carcinoma (HCC), breast cancer (BC), lung cancer (LC), or colon cancer (CC). Methods and Results: A total of 200 blood samples were obtained from cancer patients and healthy individuals. The relative expression of DNA methyltransferases (DNMTs), Ten-Eleven translocation (TET), and methionine synthase (MS) was evaluated in patients with the normal level of vitamin B12/ferritin and patients with the deficient levels of them. DNA methylation within the promoter regions was investigated of each indicated genes using the methylation-sensitive restriction enzyme HpaII and bisulfite PCR. Interestingly, the expression of DNMT1, DNMT3a, and DNMT3b was increased in patients with low levels of vitamin B12 and ferritin, while the expression of MS, TET1, and TET3 was significantly decreased. DNA methylation analysis in patients with deficient levels of vitamin B12/ferritin showed a methylated-cytosine within the location 318/CG and 385/CG in the promoter region of TET1 and TET3, respectively. Moreover, the bisulfite PCR assay further confirmed the methylation changes in the promoter region of TET1 and TET3 at the indicated locations. Conclusion: These data indicate that the deficiency in vitamin B12 and ferritin in cancer patients plays a key role in the epigenetic exchanges during cancer development.

scholarly journals P13.15 DNA methylation abnormalities in non-promoter regulatory regions are associated with invasive behavior in pituitary tumors

2019 ◽  
Vol 21 (Supplement_3) ◽  
pp. iii65-iii66
Author(s):  
M Q S Mosella ◽  
T S Sabedot ◽  
T M Malta ◽  
J Rock ◽  
M Felicella ◽  
...  
Keyword(s):  
Dna Methylation ◽  
Target Genes ◽  
Meta Analysis ◽  
Differentially Expressed Gene ◽  
Cell Movement ◽  
Pituitary Tumors ◽  
P Value ◽  
Regulatory Regions ◽  
Cpg Sites ◽  
Invasive Behavior

Abstract BACKGROUND Despite histologically benign, pituitary tumors (PT) may invade important adjacent neurovascular structures which can incur in significant comorbidities preventing a complete surgical resection and contributing to resistance to medical treatment. DNA methylation clearly stratified PT based on their functional status i.e. nonfunctioning PTs (NFPTs) from functioning PT (FPTs). However associations of methylation aberrations with invasive behavior is less clear. MATERIAL AND METHODS In order to evaluate whether DNA methylation alterations in regulatory regions other than promoter and coding regions are associated with invasive behavior we performed a meta-analysis of the genome-wide methylome of three public available PT cohorts plus our own (Illumina HumanMethylation platforms- 450K/EPIC). Pituitary specimens comprised of 43 invasive pituitary tumors (InvPT) and 37 noninvasive (NInvPT); 12 FPT and 68 NFPTs, in addition to 20 non-tumor pituitaries. RNA-seq data were available for one cohort (n=23, 12 InvPT,11NInvPT) and integrated with DNA methylation. Invasiveness criteria was based on Knosp grade >= 2 and/or sphenoid or dural invasion. RESULTS Wilcoxon Rank-sum test; Δβ=0.15; p-value <0.001 identified 58 differentially methylated CpG sites in InvPT that were mainly hypomethylated (95%) in relation to NInvPT. NInvPT methylation profile was similar to non-tumor specimens, despite its heterogeneity. Thirty-four percent (n=20) of the differentially methylated CpG sites were located within predicted enhancer regions distributed in intronic (40%), intergenic (40%) and promoter (20%) regions. Predicted enhancer-target genes were enriched for actin filament cell movement, response to starvation, growth factor stimulus and protein autophosporilation pathways. Among them, ZNF625 and INO80E were found mostly negative correlated among methylation and expression data (-0.50 and -0.48, respectively), besides DOC2A found to be one potentially differentially expressed gene under enhancer control (log2FC > 0.2, pvalue <0.05). CONCLUSION Our results suggest that methylation alterations in predicted regulatory regions, such as enhancers, annotated in non-promoter regions (introns and intergenic) may contribute to the invasive behavior of PT.

Study on DNA Methylation Status of WT1 Gene in Its Promoter Region in Hematologic Neoplasm Cell Lines.

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 4386-4386
Author(s):  
Ye Zhao ◽  
Zi-xing Chen ◽  
Shao-yan Hu ◽  
Jian-nong Cen
Keyword(s):  
Gene Expression ◽  
Dna Methylation ◽  
Cell Lines ◽  
Promoter Region ◽  
U937 Cell ◽  
Methylation Status ◽  
Gene Promoter ◽  
Epigenetic Mechanism ◽  
Wt1 Gene ◽  
Gene Promoter Region

Abstract The methylation at CpG island in the promoter region of a gene is one of the important epigenetic mechanism which regulates the gene activity. To study the DNA methylation pattern of WT1 gene promoter region within hematologic neoplastic cell lines and its correlation with WT1 gene expression by using the PCR-based methods. RT-PCR and Methylation-specific PCR were performed to study the WT1 gene expression in 8226, HL-60, Jurkat, K562, KG-1, NB4, Raji, SHI-1, U266 and U937 cell lines and the DNA methylation status in promoter region of WT1 gene. After treatment of U937 cell line by 5-aza-CdR, a demethylation inducing agent, the changes of WT1 gene expression level and the methylation status in its promter region in U937 cells was determined. Our Results showed that HL-60, K562, KG-1, NB4, SHI-1 cell lines demonstrated higher level of WT1 expression, while extremely low level was found in 8226, Jurkat, Raji, U266 and U937. The DNA hypermethylation in WT1 gene promoter region was identified in 8226, Jurkat, Raji, U266 and U937 cell lines. The WT1 gene expression in U937 was markedly enhanced after treatment with 5-aza-CdR in company with the decrease of methylated level and the increase of unmethylated level in its promoter region. These results indicate that modulation of the DNA methylation in WT1 promoter region is one of the epigenetic mechanisms to regulate its expression.

DNA methylation in the androgen receptor gene promoter region in rat prostate cancers

The Prostate ◽  
2002 ◽  
Vol 52 (1) ◽  
pp. 82-88 ◽  
Author(s):  
Satoru Takahashi ◽  
Shingo Inaguma ◽  
Michihisa Sakakibara ◽  
Young-Man Cho ◽  
Shugo Suzuki ◽  
...  
Keyword(s):  
Dna Methylation ◽  
Androgen Receptor ◽  
Promoter Region ◽  
Receptor Gene ◽  
Gene Promoter ◽  
Androgen Receptor Gene ◽  
Rat Prostate ◽  
Prostate Cancers ◽  
Gene Promoter Region

Epigenetic alterations associated with premature ovarian failure

2008 ◽  
Vol 90 ◽  
pp. S122-S123
Author(s):  
M. Ghahremani ◽  
C.W. Hanna ◽  
K.L. Bretherick ◽  
M.S. Penaherrera ◽  
M.R. Fluker ◽  
...  
Keyword(s):  
Premature Ovarian Failure ◽  
Ovarian Failure ◽  
Epigenetic Alterations
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