scholarly journals Methylation of HPV16 genome CpG sites is associated with cervix precancer and cancer

2011 ◽  
Vol 121 (1) ◽  
pp. 59-63 ◽  
Author(s):  
Chang Sun ◽  
Laura L. Reimers ◽  
Robert D. Burk
Keyword(s):  
Cpg Sites ◽  
Hpv16 Genome

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 Human Prehistoric Demography Revealed by the Polymorphic Pattern of CpG Transitions

2020 ◽  
Vol 37 (9) ◽  
pp. 2691-2698 ◽  
Author(s):  
Xiaoming Liu
Keyword(s):  
Population Dynamics ◽  
Population Expansion ◽  
Future Research ◽  
Human Populations ◽  
Neolithic Revolution ◽  
Cpg Sites ◽  
Hunting And Gathering ◽  
Genome Wide ◽  
Polymorphic Pattern ◽  
Improved Model

Abstract The prehistoric demography of human populations is an essential piece of information for illustrating our evolution. Despite its importance and the advancement of ancient DNA studies, our knowledge of human evolution is still limited, which is also the case for relatively recent population dynamics during and around the Holocene. Here, we inferred detailed demographic histories from 1 to 40 ka for 24 population samples using an improved model-flexible method with 36 million genome-wide noncoding CpG sites. Our results showed many population growth events that were likely due to the Neolithic Revolution (i.e., the shift from hunting and gathering to agriculture and settlement). Our results help to provide a clearer picture of human prehistoric demography, confirming the significant impact of agriculture on population expansion, and provide new hypotheses and directions for future research.

scholarly journals MGMT promoter methylation testing to predict overall survival in people with glioblastoma treated with temozolomide: a comprehensive meta-analysis based on a Cochrane Review

2021 ◽  
Author(s):  
Sebastian Brandner ◽  
Alexandra McAleenan ◽  
Claire Kelly ◽  
Francesca Spiga ◽  
Hung-Yuan Cheng ◽  
...  
Keyword(s):  
Overall Survival ◽  
Dna Methyltransferase ◽  
Meta Analysis ◽  
Alkylating Agents ◽  
Cochrane Review ◽  
Predictive Biomarker ◽  
Test Method ◽  
Sufficient Information ◽  
Cpg Sites ◽  
Hazard Ratios

Abstract BACKGROUND The DNA repair protein O6 methylguanine-DNA methyltransferase (MGMT) causes resistance of tumour cells to alkylating agents. It is a predictive biomarker in high grade gliomas treated with temozolomide, however there is no consensus on which test method, methylation sites, and cut-off values to use. METHODS We performed a Cochrane Review to examine studies using different techniques to measure MGMT and predict survival in glioblastoma patients treated with temozolomide. Eligible longitudinal studies included adults with glioblastoma treated with temozolomide with or without radiotherapy, or surgery; where MGMT status was determined in tumour tissue, and assessed by one or more technique; and where overall survival was an outcome parameter, with sufficient information to estimate hazard ratios. Two or more methods were compared in 32 independent cohorts with 3474 patients. RESULTS Methylation-specific PCR (MSP) and pyrosequencing (PSQ) techniques were more prognostic than immunohistochemistry for MGMT protein, and PSQ is a slightly better predictor than MSP. CONCLUSIONS We cannot draw strong conclusions about use of frozen tissue versus formalin-fixed paraffin embedded in MSP and PSQ. Also, our meta-analysis does not provide strong evidence about the best CpG sites or threshold. MSP has been studied mainly for CpG sites 76-80 and 84-87 and Pyrosequencing at CpG sites ranging from 72 to 95. A cut-off threshold of 9% for CpG sites 74-78 performed better than higher thresholds of 28% or 29% in two of three good-quality studies. 190 studies were identified presenting hazard ratios from survival analysis in patients in which MGMT methylation was measured by one technique only.

scholarly journals EXTH-65. USING METHYLATION PROFILES TO GUIDE THE REPURPOSING OF CHEMOTHERAPIES AGAINST HIGH-RISK MENINGIOMAS

2020 ◽  
Vol 22 (Supplement_2) ◽  
pp. ii101-ii101
Author(s):  
Anh Tran ◽  
Denise Scholtens ◽  
Lyndsee Zhang ◽  
Jenny Pokorny ◽  
Aneta Baran ◽  
...  
Keyword(s):  
Apoptotic Cell ◽  
Progression Free Survival ◽  
Brain Structures ◽  
Primary Brain Tumor ◽  
Molecular Characteristics ◽  
Cpg Sites ◽  
Hazard Ratios ◽  
The Us ◽  
Patient Prognosis ◽  
Raloxifene Hydrochloride

Abstract Meningioma is the most common primary brain tumor with nearly thirty thousand new cases in the US every year. While most meningiomas grow slowly, hence categorized as benign, they can still impact brain structures and result in disability or lethality. Currently, there is no widely accepted chemotherapy for meningioma, and our understanding of the disease’s molecular characteristics is very limited. In this study, we aimed to identify druggable molecular targets for repurposing of chemotherapies against meningiomas. We analyzed previously published dataset of 493 meningioma patients by Felix Sahm et al (Lancet Oncology, 2017) for association with progression-free survival (PFS) and identified associations of methylation at individual CpG sites as detected by the Illumina 450k platform with PFS. Subsequently, we searched for candidate drugs targeting the pathways linked to poor patient prognosis. Our analyses indicated 981 genes for which methylation of mapped CpG sites was found to be consistently associated with shorter PFS (positive hazard ratios (HRs)) and with longer PFS (negative HRs) at FDR-adjusted p &lt; 0.05. Using Cytoscape/Reactome FI app, we cross-referenced current cancer drugs that target these and identified docetaxel and raloxifene hydrochloride as potential candidates. In our vitro study, docetaxel caused apoptotic cell death in established and primary patient meningioma lines of various grades. IC50s of docetaxel in the sixteen meningioma cell lines tested ranged from 0.8nM to 4.4mM, which partially corresponded to the growth rates of these cells. Our study will advance our understanding of molecular pathways driving meningioma and identify potential targeted therapies to bridge the current gap in treatment of the disease.

scholarly journals Screening the genome for HCC-specific CpG methylation signatures as biomarkers for diagnosis and prognosis evaluation

2021 ◽  
Vol 14 (1) ◽  
Author(s):  
Rui-kun Zhang ◽  
Jia-lin Liu
Keyword(s):  
Cox Regression ◽  
Malignant Tumors ◽  
Gene Expression Omnibus ◽  
The Cancer Genome Atlas ◽  
Survival Prediction ◽  
Training Set ◽  
Cpg Sites ◽  
Diagnosis And Prognosis ◽  
Patient Prognosis ◽  
Prognosis Evaluation

Abstract Background Hepatocellular carcinoma (HCC) is one of the most common and invasive malignant tumors in the world. The change in DNA methylation is a key event in HCC. Methods Methylation datasets for HCC and 17 other types of cancer were downloaded from The Cancer Genome Atlas (TCGA). The CpG sites with large differences in methylation between tumor tissues and paracancerous tissues were identified. We used the HCC methylation dataset downloaded from the TCGA as the training set and removed the overlapping sites among all cancer datasets to ensure that only CpG sites specific to HCC remained. Logistic regression analysis was performed to select specific biomarkers that can be used to diagnose HCC, and two datasets—GSE157341 and GSE54503—downloaded from GEO as validation sets were used to validate our model. We also used a Cox regression model to select CpG sites related to patient prognosis. Results We identified 6 HCC-specific methylated CpG sites as biomarkers for HCC diagnosis. In the training set, the area under the receiver operating characteristic (ROC) curve (AUC) for the model containing all these sites was 0.971. The AUCs were 0.8802 and 0.9711 for the two validation sets from the GEO database. In addition, 3 other CpG sites were analyzed and used to create a risk scoring model for patient prognosis and survival prediction. Conclusions Through the analysis of HCC methylation datasets from the TCGA and Gene Expression Omnibus (GEO) databases, potential biomarkers for HCC diagnosis and prognosis evaluation were ascertained.

scholarly journals Birthweight DNA methylation signatures in infant saliva

2021 ◽  
Vol 13 (1) ◽  
Author(s):  
Chiara Moccia ◽  
Maja Popovic ◽  
Elena Isaevska ◽  
Valentina Fiano ◽  
Morena Trevisan ◽  
...  
Keyword(s):  
Dna Methylation ◽  
Cord Blood ◽  
Gestational Age ◽  
Low Birthweight ◽  
Continuous Variable ◽  
Linear Regression Models ◽  
Association Analyses ◽  
Cpg Sites ◽  
Adverse Health Outcomes ◽  
The Look

Abstract Background Low birthweight has been repeatedly associated with long-term adverse health outcomes and many non-communicable diseases. Our aim was to look-up cord blood birthweight-associated CpG sites identified by the PACE Consortium in infant saliva, and to explore saliva-specific DNA methylation signatures of birthweight. Methods DNA methylation was assessed using Infinium HumanMethylation450K array in 135 saliva samples collected from children of the NINFEA birth cohort at an average age of 10.8 (range 7–17) months. The association analyses between birthweight and DNA methylation variations were carried out using robust linear regression models both in the exploratory EWAS analyses and in the look-up of the PACE findings in infant saliva. Results None of the cord blood birthweight-associated CpGs identified by the PACE Consortium was associated with birthweight when analysed in infant saliva. In saliva EWAS analyses, considering a false discovery rate p-values < 0.05, birthweight as continuous variable was associated with DNA methylation in 44 CpG sites; being born small for gestational age (SGA, lower 10th percentile of birthweight for gestational age according to WHO reference charts) was associated with DNA methylation in 44 CpGs, with only one overlapping CpG between the two analyses. Despite no overlap with PACE results at the CpG level, two of the top saliva birthweight CpGs mapped at genes associated with birthweight with the same direction of the effect also in the PACE Consortium (MACROD1 and RPTOR). Conclusion Our study provides an indication of the birthweight and SGA epigenetic salivary signatures in children around 10 months of age. DNA methylation signatures in cord blood may not be comparable with saliva DNA methylation signatures at about 10 months of age, suggesting that the birthweight epigenetic marks are likely time and tissue specific.

scholarly journals Age-related differences in monocyte DNA methylation and immune function in healthy Kenyan adults and children

2021 ◽  
Vol 18 (1) ◽  
Author(s):  
Katherine R. Dobbs ◽  
Paula Embury ◽  
Emmily Koech ◽  
Sidney Ogolla ◽  
Stephen Munga ◽  
...  
Keyword(s):  
Gene Expression ◽  
Dna Methylation ◽  
Young Adults ◽  
Expression Profiles ◽  
Gene Expression Profiles ◽  
Innate Immune ◽  
Inflammatory Gene Expression ◽  
Cpg Sites ◽  
Age Related ◽  
Adults And Children

Abstract Background Age-related changes in adaptive and innate immune cells have been associated with a decline in effective immunity and chronic, low-grade inflammation. Epigenetic, transcriptional, and functional changes in monocytes occur with aging, though most studies to date have focused on differences between young adults and the elderly in populations with European ancestry; few data exist regarding changes that occur in circulating monocytes during the first few decades of life or in African populations. We analyzed DNA methylation profiles, cytokine production, and inflammatory gene expression profiles in monocytes from young adults and children from western Kenya. Results We identified several hypo- and hyper-methylated CpG sites in monocytes from Kenyan young adults vs. children that replicated findings in the current literature of differential DNA methylation in monocytes from elderly persons vs. young adults across diverse populations. Differentially methylated CpG sites were also noted in gene regions important to inflammation and innate immune responses. Monocytes from Kenyan young adults vs. children displayed increased production of IL-8, IL-10, and IL-12p70 in response to TLR4 and TLR2/1 stimulation as well as distinct inflammatory gene expression profiles. Conclusions These findings complement previous reports of age-related methylation changes in isolated monocytes and provide novel insights into the role of age-associated changes in innate immune functions.

scholarly journals DNA Methylation in LIME1 and SPTBN2 Genes Is Associated with Attention Deficit in Children

Children ◽  
2021 ◽  
Vol 8 (2) ◽  
pp. 92
Author(s):  
Sung-Chou Li ◽  
Ho-Chang Kuo ◽  
Lien-Hung Huang ◽  
Wen-Jiun Chou ◽  
Sheng-Yu Lee ◽  
...  
Keyword(s):  
Dna Methylation ◽  
Attention Deficit ◽  
Performance Test ◽  
Neurodevelopmental Disorder ◽  
Continuous Performance Test ◽  
Attention Deficits ◽  
Clinical Settings ◽  
Hyperactivity Disorder ◽  
Cpg Sites ◽  
Healthy Control

DNA methylation levels are associated with neurodevelopment. Attention-deficit/hyperactivity disorder (ADHD), characterized by attention deficits, is a common neurodevelopmental disorder. We used methylation microarray and pyrosequencing to detect peripheral blood DNA methylation markers of ADHD. DNA methylation profiling data from the microarray assays identified potential differentially methylated CpG sites between 12 ADHD patients and 9 controls. Five candidate CpG sites (cg00446123, cg20513976, cg07922513, cg17096979, and cg02506324) in four genes (LIME1, KCNAB2, CAPN9, and SPTBN2) were further examined with pyrosequencing. The attention of patients were tested using the Conners’ Continuous Performance Test (CPT). In total, 126 ADHD patients with a mean age of 9.2 years (78.6% males) and 72 healthy control subjects with a mean age of 9.3 years (62.5% males) were recruited. When all participants were categorized by their CPT performance, the DNA methylation levels in LIME1 (cg00446123 and cg20513976) were found to be significantly higher and those in SPTBN2 (cg02506324) were significantly lower in children with worse CPT performance. Therefore, DNA methylation of two CpG sites in LIME1 and one CpG site in SPTBN2 is associated with attention deficits in children. DNA methylation biomarkers may assist in identifying attention deficits of children in clinical settings.

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