Clinical Epigenetics

http://link.springer.com/journal/13148

List of Papers (Total 596)

Analysis of the DNA methylation level of cancer-related genes in colorectal cancer and the surrounding normal mucosa

Background Two molecular pathways promote the development of colorectal cancer (CRC). One is termed “microsatellite stable” (MSS) whereas the other is characterized by “microsatellite instability” (MSI or MIN). In addition, the CpG island methylation phenotype is known to be an important alteration as a third molecular type. Thus, DNA methylation is thought to provide potential...

Epigenome-wide association of myocardial infarction with DNA methylation sites at loci related to cardiovascular disease

Background Development of cardiovascular disease (CVD), including coronary artery disease, arrhythmia, and ischemic stroke, depends on environmental and genetic factors. To investigate the epigenetic basis of myocardial infarction (MI), we performed an epigenome-wide association study for this condition in elderly Japanese subjects. A total of 192 case subjects with MI and 192...

Genetic heterogeneity of patients with suspected Silver-Russell syndrome: genome-wide copy number analysis in 82 patients without imprinting defects

Background Silver-Russell syndrome (SRS) is a rare congenital disorder characterized by pre- and postnatal growth failure and dysmorphic features. Recently, pathogenic copy number variations (PCNVs) and imprinting defects other than hypomethylation of the H19-differentially methylated region (DMR) and maternal uniparental disomy chromosome 7 have been reported in patients with...

Circulating nucleosomes as new blood-based biomarkers for detection of colorectal cancer

Background Colonoscopy is currently widely accepted as the gold standard for detection of colorectal cancer (CRC) providing detection of up to 95% of pre-cancerous lesions during the procedure. However, certain limitations exist in most countries including cost and access to the procedure. Moreover, colonoscopy is an invasive technique with risk inherent to the endoscopic...

Epigenetic modifications of the immune-checkpoint genes CTLA4 and PDCD1 in non-small cell lung cancer results in increased expression

Targeting checkpoint inhibitors using monoclonal antibodies results in significantly better outcome of cancer patients compared to conventional chemotherapy. However, the current companion diagnostics to predict response is so far suboptimal, since they base on more or less reliable immunohistochemical approaches. In order to overcome these limitations, we analyzed epigenetic...

Associations between maternal risk factors of adverse pregnancy and birth outcomes and the offspring epigenetic clock of gestational age at birth

BackgroundA recent study has shown that it is possible to accurately estimate gestational age (GA) at birth from the DNA methylation (DNAm) of fetal umbilical cord blood/newborn blood spots. This DNAm GA predictor may provide additional information relevant to developmental stage. In 814 mother-neonate pairs, we evaluated the associations between DNAm GA and a number of maternal...

Genome-wide DNA methylation analysis reveals loci that distinguish different types of adipose tissue in obese individuals

Background Epigenetic mechanisms provide an interface between environmental factors and the genome and are known to play a role in complex diseases such as obesity. These mechanisms, including DNA methylation, influence the regulation of development, differentiation and the establishment of cellular identity. Here we employ two approaches to identify differential methylation...

Integrated data analysis reveals potential drivers and pathways disrupted by DNA methylation in papillary thyroid carcinomas

Background Papillary thyroid carcinoma (PTC) is a common endocrine neoplasm with a recent increase in incidence in many countries. Although PTC has been explored by gene expression and DNA methylation studies, the regulatory mechanisms of the methylation on the gene expression was poorly clarified. In this study, DNA methylation profile (Illumina HumanMethylation 450K) of 41 PTC...

The CpG island methylator phenotype is concordant between primary colorectal carcinoma and matched distant metastases

Background The CpG island methylator phenotype (CIMP) in stage III colon cancer (CRC) has been associated with improved survival after treatment with adjuvant irinotecan-based chemotherapy. In this analysis, we determine whether CIMP status in the primary CRC is concordant with the CIMP status of matched metastases in order to determine if assessment of CIMP status in the primary...

Regional differences in mitochondrial DNA methylation in human post-mortem brain tissue

Background DNA methylation is an important epigenetic mechanism involved in gene regulation, with alterations in DNA methylation in the nuclear genome being linked to numerous complex diseases. Mitochondrial DNA methylation is a phenomenon that is receiving ever-increasing interest, particularly in diseases characterized by mitochondrial dysfunction; however, most studies have...

Epigenetic changes in blood leukocytes following an omega-3 fatty acid supplementation

Background Omega-3 polyunsaturated fatty acids (n-3 FAs) have several beneficial effects on cardiovascular (CV) disease risk factors. These effects on CV risk profile may be mediated by several factors, including epigenetic modifications. Our objective is to investigate, using genome-wide DNA methylation analyses, methylation changes following an n-3 FA supplementation in...

Circulating unmethylated insulin DNA as a potential non-invasive biomarker of beta cell death in type 1 Diabetes: a review and future prospect

BackgroundThe early detection of type 1 diabetes (T1D) largely depends on a reliable approach to monitor β cell loss. An effective way to evaluate the decline of β cell mass would allow early preventative intervention to preserve insulin secretion.Main bodyRecent progress in the development of novel biomarkers, based on tissue-specific methylation patterns, has inspired relevant...

Aberrant DNA methylation and expression of SPDEF and FOXA2 in airway epithelium of patients with COPD

Background Goblet cell metaplasia, a common feature of chronic obstructive pulmonary disease (COPD), is associated with mucus hypersecretion which contributes to the morbidity and mortality among patients. Transcription factors SAM-pointed domain-containing Ets-like factor (SPDEF) and forkhead box protein A2 (FOXA2) regulate goblet cell differentiation. This study aimed to (1...

Epigenetic assays for chemical biology and drug discovery

The implication of epigenetic abnormalities in many diseases and the approval of a number of compounds that modulate specific epigenetic targets in a therapeutically relevant manner in cancer specifically confirms that some of these targets are druggable by small molecules. Furthermore, a number of compounds are currently in clinical trials for other diseases including...

Cord blood hematopoietic cells from preterm infants display altered DNA methylation patterns

Background Premature infants are highly vulnerable to infection. This is partly attributable to the preterm immune system, which differs from that of the term neonate in cell composition and function. Multiple studies have found differential DNA methylation (DNAm) between preterm and term infants’ cord blood; however, interpretation of these studies is limited by the confounding...

36 h fasting of young men influences adipose tissue DNA methylation of LEP and ADIPOQ in a birth weight-dependent manner

Background Subjects born with low birth weight (LBW) display a more energy-conserving response to fasting compared with normal birth weight (NBW) subjects. However, the molecular mechanisms explaining these metabolic differences remain unknown. Environmental influences may dynamically affect epigenetic marks, also in postnatal life. Here, we aimed to study the effects of short...

DNA methylation profiling in peripheral lung tissues of smokers and patients with COPD

Background Epigenetics changes have been shown to be affected by cigarette smoking. Cigarette smoke (CS)-mediated DNA methylation can potentially affect several cellular and pathophysiological processes, acute exacerbations, and comorbidity in the lungs of patients with chronic obstructive pulmonary disease (COPD). We sought to determine whether genome-wide lung DNA methylation...

Differential adipokine DNA methylation and gene expression in subcutaneous adipose tissue from adult offspring of women with diabetes in pregnancy

Background Offspring of women with diabetes in pregnancy are at increased risk of type 2 diabetes mellitus (T2DM), potentially mediated by epigenetic mechanisms. The adipokines leptin, adiponectin, and resistin (genes: LEP, ADIPOQ, RETN) play key roles in the pathophysiology of T2DM. We hypothesized that offspring exposed to maternal diabetes exhibit alterations in epigenetic...

Clusterization in head and neck squamous carcinomas based on lncRNA expression: molecular and clinical correlates

Background Long non-coding RNAs (lncRNAs) have emerged as key players in a remarkably variety of biological processes and pathologic conditions, including cancer. Next-generation sequencing technologies and bioinformatics procedures predict the existence of tens of thousands of lncRNAs, from which we know the functions of only a handful of them, and very little is known in cancer...

Assessing alternative base substitutions at primer CpG sites to optimise unbiased PCR amplification of methylated sequences

Background Determining the role of DNA methylation in various biological processes is dependent on the accurate representation of often highly complex patterns. Accurate representation is dependent on unbiased PCR amplification post bisulfite modification, regardless of methylation status of any given epiallele. This is highly dependent on primer design. Particular difficulties...

Aberrant DNA methylation in melanoma: biomarker and therapeutic opportunities

Aberrant DNA methylation is an epigenetic hallmark of melanoma, known to play important roles in melanoma formation and progression. Recent advances in genome-wide methylation methods have provided the means to identify differentially methylated genes, methylation signatures, and potential biomarkers. However, despite considerable effort and advances in cataloging methylation...

Validation of the MethylationEPIC BeadChip for fresh-frozen and formalin-fixed paraffin-embedded tumours

DNA methylation is the most studied epigenetic modification due to its role in regulating gene expression, and its involvement in the pathogenesis of cancer and several diseases upon aberrations in methylation. The method of choice to evaluate genome-wide methylation has been the Illumina HumanMethylation450 BeadChip (450K), but it was recently replaced with the MethylationEPIC...

Interaction between prenatal pesticide exposure and a common polymorphism in the PON1 gene on DNA methylation in genes associated with cardio-metabolic disease risk—an exploratory study

BackgroundPrenatal environmental conditions may influence disease risk in later life. We previously found a gene-environment interaction between the paraoxonase 1 (PON1) Q192R genotype and prenatal pesticide exposure leading to an adverse cardio-metabolic risk profile at school age. However, the molecular mechanisms involved have not yet been resolved. It was hypothesized that...

DNA methylation signatures for 2016 WHO classification subtypes of diffuse gliomas

BackgroundGlioma is the most common of all primary brain tumors with poor prognosis and high mortality. The 2016 World Health Organization classification of the tumors of central nervous system uses molecular parameters in addition to histology to redefine many tumor entities. The new classification scheme divides diffuse gliomas into low-grade glioma (LGG) and glioblastoma (GBM...