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Exploring DNA methylation profiles in the pathogenesis of human osteoporosis via whole-genome bisulfite sequencing.

Osteoporosis is a widespread metabolic bone disorder characterized by diminished bone mass, deteriorated microarchitecture, and increased bone fragility, resulting in elevated fracture risk. This condition adversely affects quality of life and is associated with higher mortality. Growing evidence indicates that DNA methylation serves as a key epigenetic mechanism regulating bone metabolism-related gene expression and may thereby influence osteoporosis pathogenesis. However, the specific relationship between DNA methylation and osteoporosis remains to be fully elucidated. In this hypothesis‑gen…

Prognostic significance of O6-methylguanine-DNA methyltransferase promoter methylation status in isocitrate dehydrogenase-mutant glioma.

BACKGROUND: The prognostic and predictive value of O6-methylguanine-DNA methyltransferase promoter (MGMTp) methylation is not well established in isocitrate dehydrogenase (IDH)-mutant gliomas. This study evaluates the survival impact of MGMTp and other clinical, molecular, and radiologic variables in low-grade and high-grade IDH-mutant gliomas. METHODS: We retrospectively evaluated 520 consecutive adult patients treated for an initial diagnosis of IDH-mutant glioma, of any histological grade, at two large academic institutions. MGMTp methylation was evaluated by methylation-specific polymeras

DNA methylation-mediated downregulation of MEIS2 correlates with tumor development and progression in gastric cancer.

BACKGROUND: Gastric cancer (GC) is a molecularly heterogeneous disease with poor prognosis. DNA methylation plays a critical role in its pathogenesis, and Homeobox genes are known to be frequently dysregulated through epigenetic mechanisms in various cancers. However, the role of the homeobox gene MEIS2 in GC remains unclear. METHOD: Integrated bioinformatics analysis of RNA-seq and DNA methylation data from TCGA and a K19-Wnt1/C2mE transgenic (Gan) mouse model identified MEIS2 as a candidate gene. Its clinical relevance was assessed using GEO datasets and a clinical cohort of 293 GC patients…

Continuous DNA methylation deconvolution-based surrogate for B-cell differentiation state in chronic lymphocytic leukemia.

BACKGROUND: Chronic lymphocytic leukemia (CLL) is clinically divided categorically into IGHV mutated (M-CLL) and IGHV unmutated (U-CLL) subtypes. We aimed to generate a continuous metric of CLL epigenetic state to correspond to the many steps of B-cell differentiation from which CLL neoplasms may arise. METHODS: We measured genome-scale DNA methylation in purified CLL samples (n = 89) and utilized reference-based cell deconvolution techniques to develop a continuous metric of epigenetic similarity across a B-naive-like to B-memory-like scale (B-Index). We used B-Index to find epigenome-wide c…

A framework for using DNA methylation-based modelling for the clinical management of cranial meningioma.

BACKGROUND: DNA methylation profiling can be used to robustly predict postsurgical outcomes and response to radiotherapy (RT) for meningioma patients. To allow for seamless integration of these complementary models into clinical practice, a practical framework is needed. METHODS: We leveraged a cohort of nearly 2000 surgically-treated meningiomas with DNA methylation profiling and clinical outcomes data. Existing methylation-based prediction models were dichotomized to yield four risk groups: low and high recurrent risk, each with RT sensitive and resistant subgroups. Risk groups were correla…

Detection of recurrent endometrial cancer via DNA methylation analysis of cervicovaginal self-samples and urine.

DNA methylation analysis of self-collected samples has shown potential for primary endometrial cancer detection. Here, we aimed to explore DNA methylation testing as a non-invasive alternative for post-treatment surveillance. Endometrial cancer patients (n = 43) without recurrence collected pre- and post-treatment cervicovaginal self-samples and urine at home. Additionally, 17 patients with recurrence provided these samples at the time of recurrence. Healthy controls were used as reference. In total, 207 cervicovaginal self-samples and 203 urine samples were tested for nine markers (ADCYAP1, B…

Effects of 6-months of SSRI use on DNA-methylation and gene expression in blood.

BACKGROUND: Selective serotonin reuptake inhibitors (SSRIs) are a recommended first line medication for the treatment of major depressive disorder, due to higher tolerability and lower risk of adverse effects than other antidepressants. The mechanisms by which SSRIs reduce depressive symptoms are not well understood, but are hypothesised to include direct effects on serotonin signalling and synaptic remodelling, and indirect effects on inflammation. Indirect or off-target effects may be detectable in blood and can be investigated using methylome- and transcriptome-wide approaches. METHODS: Th

Challenging anatomical paradigms: unexpected supratentorial localization of posterior fossa B ependymomas identified by DNA methylation.

Molecular subgroups of ependymomas are strongly associated with their primary anatomical compartments, namely the supratentorial region, posterior fossa and spine locations. Although it is generally accepted that posterior fossa ependymomas may arise from radial glia-like progenitor cells, the precise cellular origin of the distinct posterior fossa molecular subgroups remains to be determined. Given that DNA methylation profile strongly recapitulates developmental lineage and the cell of origin, the characterization of unexpectedly located molecular subgroups of ependymomas may provide insight…

Integrative genetic analysis identifies shared regulation of DNA methylation and gene expression in migraine risk.

BACKGROUND: Migraine affects approximately 14% of adults, but the molecular mechanisms underlying susceptibility remain incompletely understood. Although genome-wide association studies (GWAS) have identified many migraine risk loci, translating these associations into biological insight remains challenging. Environmental and physiological migraine triggers, including hormones, diet and stress, may act partly through epigenetic mechanisms such as DNA methylation. Because many migraine risk variants are non-coding and may influence disease through regulatory effects, integrating genetic associa…

Can DNA Methylation in Peritumoral and Contralateral Breast Tissue Predict Recurrence or Second Breast Cancers?

Despite major advances in early breast cancer detection and therapeutic strategies, locoregional and distant recurrences, as well as the dev … tissue, which may harbor clinically relevant molecular alterations. Emerging evidence suggests that DNA methylation changes can be detected in the adjacent and contralateral breast tissue and reflect early steps of carcinogenesis or predisposition to tumor development. This phenomenon, often referred to as field cancerization, raises new questions about the dynam …

The Double-Edged Sword of Genomic DNA Methylation: Orchestrating Gastric Carcinogenesis and Shaping Precision Oncology.

This article systematically elaborates on the dual role of DNA methylation in the initiation and progression of gastric cancer and its potential clinical applications in precision oncology. As a core epigenetic mechanism, DNA methylation drives the multistage development of gastric cancer through the coordinated dysregulation of genome-wide hypomethylation and promoter-specific hypermethylation, playing a key role in chronic inflammation and epigenetic reprogramming, particularly in the context of Helicobacter pylori infection. The article focuses on analyzing the central pathogenic mechanisms…

Площадь метилирования ДНК клеток цереброспинальной жидкости в множестве склероза: исследование эпигеномной ассоциации.

Множественный склероз (MS) является хроническим воспалительным заболеванием центральной нервной системы, в которой метилация ДНК может увязывать генетические и экологические факторы риска. Methods: Мы профилировали содержание метилации ДНК по всему геному в клетках цереброспиновой жидкости (CSF) у людей с MS (pwMS) и совпадающими контрольными устройствами. Дифференцированные метилированные позиции (DMP) и регионы (DMR) были интегрированы с транскриптомными данными, аннотациями клеточного хроматина Т и анализом путей. Выражение гамма-протокадерина (ПХДГ) было оценено в первичных подмножествах C

Совпадение в аннотации оригинала
BACKGROUND: Multiple sclerosis (MS) is a chronic inflammatory disease of the central nervous system in which DNA methylation may link genetic and environmental risk factors. METHODS: We profiled genome-wide DNA methylation in cerebrospinal fluid (CSF) cells from people with MS (pwMS) and matched controls. Differentially methylated positions (DMPs) and regio…

Maternal per- and polyfluoroalkyl substance concentrations and placental DNA methylation of thyroid hormone-related genes.

Studies suggested that per- and polyfluoroalkyl substances (PFAS) may have adverse effects on fetus by altering placental DNA methylation. In the study, we explored associations of maternal PFAS concentrations with placental DNA methylation of thyroid hormone (TH)-related genes and the potential mediating role of DNA methylation levels in PFAS-fetal TH associations. We measured PFAS concentrations in maternal plasma in early pregnancy and levels of total triiodothyronine (TT3), total thyroxine (TT4), free triiodothyronine (FT3), free thyroxine (FT4), and thyroid stimulating hormone (TSH) in co…

Mapping the landscape of cell type-dependent genetic regulation of DNA methylation across human tissues.

DNA methylation (DNAm) is an epigenetic modification involved in gene regulation. DNAm quantitative trait loci (mQTLs) have been identified in many tissues, but bulk-tissue studies obscure cell type-specific effects. Here, we present the first multi-tissue landscape of cell type-dependent regulation of DNAm in humans by mapping cell type-interaction mQTLs (imQTLs) across seven tissue types (breast, colon, lung, ovary, prostate, kidney, and whole blood), identifying 3,150 imQTLs. Inter-individual variability in cell type proportion, rather than mean proportion, was most associated with imQTL di…

DNA methylation-induced suppression of PRDM16 in colorectal cancer metastasis through the PPARγ/EMT pathway.

BACKGROUND: PR/SET domain 16 (PRDM16) is an important transcription factor in the differentiation process of brown adipocytes, which plays a … study found that methylation level of PRDM16 was associated with CRC and lung metastasis of CRC by DNA methylation sequencing. Furthermore, we identified methylation sites within the promoter region of PRDM16. PRDM16 expression was significantly lower in human CRC tissue samples and dramatically associated with tumor size, T stage, overall survival rates and dis …

Generation of Insulin-Producing Alpha TC1-6 Cells Using EpiCRISPR System for Targeted DNA Methylation.

Diabetes lacks concrete curative strategies due to diverse aetiologies and, therefore, represents the perfect candidate for cell replacement … new beta cells. In this protocol, we used the modular epigenetic CRISPR/dCas9 toolbox for targeted DNA methylation (EpiCRISPR) and silencing of the Arx gene (Aristaless Related Homeobox, Arx), which is essential for the maintenance of alpha cell identity. Methylation-based silencing of Arx initiates the reprogramming of pancreatic alpha cells into insulin-produc …

Genome-Wide Blood DNA Methylation Profiling in Birch Pollen Allergic Patients Undergoing Allergen-Specific Immunotherapy.

BACKGROUND: Until now, no study has investigated the impact of allergen immunotherapy (AIT) on genome-wide DNA methylation in a longitudinal set-up. Herein, we investigated whether differences in DNA methylation occur in birch pollen allergic patients undergoing 6 months of birch pollen AIT, assessed alterations in methylation-based blood cell type composition, and correlated DNA methylation to serological AIT biomarkers. METHODS: We performed genome-wide DNA-methylation analysis on bisulfite-converted DNA derived from whole blood samples of 16 birch pollen-allergic patients (pre-/post-birch …

DNA methylation-based forensic framework for age prediction and body fluid identification using nanopore sequencing.

Forensic DNA phenotyping applies genetic and epigenetic markers to infer biogeographical ancestry, physical appearance traits, and biological age, particularly when conventional methods fail to identify a suspect or victim. DNA methylation, a key epigenetic modification, is especially valuable for age estimation and due to its tissue-specific patterns also for body fluid identification, with the latter aiding in crime scene reconstruction. Current MPS-based methylation sample analyses require time-consuming, multi-step processing, while Nanopore sequencing offers a promising alternative by ena…