Clinical Epigenetics最新文献

{"title":"Maternal asthma and newborn DNA methylation.","authors":"Casper-Emil Tingskov Pedersen, Thanh T Hoang, Jianping Jin, Anna Starnawska, Raquel Granell, Hannah R Elliott, Anke Huels, Heather J Zar, Dan J Stein, Yining Zhang, Herman T den Dekker, Liesbeth Duijts, Janine F Felix, Júlia Sangüesa, Mariona Bustamante, Maribel Casas, Martine Vrijheid, Latha Kadalayil, Faisal I Rezwan, Hasan Arshad, John W Holloway, Stefan Röder, Ana C Zenclussen, Gunda Herberth, Nicklas Heine Staunstrup, Henriette Thisted Horsdal, Jonathan Mill, Eilis Hannon, Isabella Annesi-Maesano, Giancarlo Pesce, Nour Baïz, Barbara Heude, Sahra Hosseinian-Mohazzab, Carrie V Breton, Sophia Harlid, Justin Harbs, Magnus Domellof, Christina West, Edwina Yeung, Xuehuo Zeng, Wenche Nystad, Siri E Håberg, Maria C Magnus, Diana Schendel, Stephanie J London, Klaus Bønnelykke","doi":"10.1186/s13148-025-01858-4","DOIUrl":"https://doi.org/10.1186/s13148-025-01858-4","url":null,"abstract":"<p><strong>Background: </strong>Prenatal exposure to maternal asthma may influence DNA methylation patterns in offspring, potentially affecting their susceptibility to later diseases including asthma.</p><p><strong>Objective: </strong>To investigate the relationship between parental asthma and newborn blood DNA methylation.</p><p><strong>Methods: </strong>Epigenome-wide association analyses were conducted in 13 cohorts on 7433 newborns with blood methylation data from the Illumina450K or EPIC array. We used fixed effects meta-analyses to identify differentially methylated CpGs (DMCs) and comb-p to identify differentially methylated regions (DMRs) associated with maternal asthma during pregnancy and maternal asthma ever. Paternal asthma was analyzed for comparison. Models were adjusted for covariates and cell-type composition. We examined whether implicated sites related to gene expression analyses in publicly available data for childhood blood and adult lung.</p><p><strong>Results: </strong>We identified 27 CpGs associated with maternal asthma during pregnancy at False Discovery Rate < 0.05 but none for maternal asthma ever. Two distinct CpGs were associated with paternal asthma. We observed 5 DMRs associated with maternal asthma during pregnancy 3 associated with maternal asthma ever and 13 DMRs associated with paternal asthma. Gene expression analysis using data in blood from 832 children and lung from 424 adults showed associations between identified DMCs using maternal asthma and expression of several genes, including HLA genes and HOXA5, previously implicated in asthma or lung function.</p><p><strong>Conclusion: </strong>Parental asthma, especially maternal asthma during pregnancy, may be associated with alterations in newborn DNA methylation. These findings might shed light on underlying mechanisms for asthma susceptibility.</p>","PeriodicalId":10366,"journal":{"name":"Clinical Epigenetics","volume":"17 1","pages":"79"},"PeriodicalIF":4.8,"publicationDate":"2025-05-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12065361/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143962242","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Genetic and environmental contributions to epigenetic aging across adolescence and young adulthood.","authors":"Dmitry V Kuznetsov, Yixuan Liu, Alicia M Schowe, Darina Czamara, Jana Instinske, Charlotte K L Pahnke, Markus M Nöthen, Frank M Spinath, Elisabeth B Binder, Martin Diewald, Andreas J Forstner, Christian Kandler, Bastian Mönkediek","doi":"10.1186/s13148-025-01880-6","DOIUrl":"10.1186/s13148-025-01880-6","url":null,"abstract":"<p><strong>Background: </strong>Epigenetic aging estimators commonly track chronological and biological aging, quantifying its accumulation (i.e., epigenetic age acceleration) or speed (i.e., epigenetic aging pace). Their scores reflect a combination of inherent biological programming and the impact of environmental factors, which are suggested to vary at different life stages. The transition from adolescence to adulthood is an important period in this regard, marked by an increasing and, then, stabilizing epigenetic aging variance. Whether this pattern arises from environmental influences or genetic factors is still uncertain. This study delves into understanding the genetic and environmental contributions to variance in epigenetic aging across these developmental stages. Using twin modeling, we analyzed four estimators of epigenetic aging, namely Horvath Acceleration, PedBE Acceleration, GrimAge Acceleration, and DunedinPACE, based on saliva samples collected at two timepoints approximately 2.5 years apart from 976 twins of four birth cohorts (aged about 9.5, 15.5, 21.5, and 27.5 years at first and 12, 18, 24, and 30 years at second measurement occasion).</p><p><strong>Results: </strong>Half to two-thirds (50-68%) of the differences in epigenetic aging were due to unique environmental factors, indicating the role of life experiences and epigenetic drift, besides measurement error. The remaining variance was explained by genetic (Horvath Acceleration: 24%; GrimAge Acceleration: 32%; DunedinPACE: 47%) and shared environmental factors (Horvath Acceleration: 26%; PedBE Acceleration: 47%). The genetic and shared environmental factors represented the primary sources of stable differences in corresponding epigenetic aging estimators over 2.5 years. Age moderation analyses revealed that the variance due to individually unique environmental sources was smaller in younger than in older cohorts in epigenetic aging estimators trained on chronological age (Horvath Acceleration: 47-49%; PedBE Acceleration: 33-68%). The variance due to genetic contributions, in turn, potentially increased across age groups for epigenetic aging estimators trained in adult samples (Horvath Acceleration: 18-39%; GrimAge Acceleration: 24-43%; DunedinPACE: 42-57%).</p><p><strong>Conclusions: </strong>Transition to adulthood is a period of the increasing variance in epigenetic aging. Both environmental and genetic factors contribute to this trend. The degree of environmental and genetic contributions can be partially explained by the design of epigenetic aging estimators.</p>","PeriodicalId":10366,"journal":{"name":"Clinical Epigenetics","volume":"17 1","pages":"78"},"PeriodicalIF":4.8,"publicationDate":"2025-05-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12060359/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143993745","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Investigating the mechanisms by which low NAT1 expression in tumor cells contributes to chemo-resistance in colorectal cancer.","authors":"Zheng Yuan, Kai Fang, Xinsheng Miao, Yan Zhang, Menghui Gu, Wei Xu, Hao Li, Dawei Zhu, Jiahui Zhou, Jian Sun, Xinhua Gu","doi":"10.1186/s13148-025-01882-4","DOIUrl":"https://doi.org/10.1186/s13148-025-01882-4","url":null,"abstract":"&lt;p&gt;&lt;strong&gt;Background: &lt;/strong&gt;In the therapeutic landscape of colorectal cancer (CRC), chemo-resistance poses a significant and prevalent obstacle that complicates treatment efficacy and patient outcomes. Over time, cancer cells can develop mechanisms to resist the toxic effects of chemo-therapy drugs, leading to reduced sensitivity or complete insensitivity to these agents. The enzyme Arylamine N-acetyltransferase 1 (NAT1) has emerged as a promising target in strategies aimed at overcoming this challenge. NAT1 is involved in the metabolism of various xenobiotics, including some chemotherapeutic agents. Understanding the complex interactions between NAT1 and chemotherapeutic agents, as well as the molecular mechanisms underlying chemo-resistance, is crucial for the development of novel therapeutic approaches.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Objective: &lt;/strong&gt;This study aimed to assess the role of NAT1 in mediating chemo-resistance in CRC, with the goal of identifying novel strategies to overcome this clinical challenge.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Methods: &lt;/strong&gt;We conducted a comprehensive analysis using various bioinformatics tools and in vitro experiments to evaluate the effect of NAT1 expression on chemo-resistance in CRC. Furthermore, we employed a multi-omics approach, including metabolomics and next-generation sequencing, to uncover the mechanisms by which NAT1 influences chemo-resistance. Additionally, we utilized single-cell RNA sequencing (scRNA-seq), the Cellchat assay, and western blot to explore the intercellular communication between tumor and endothelial cells in the context of anti-PD-1 therapy and NAT1's impact.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Results: &lt;/strong&gt;Our study reveals that decreased NAT1 expression in CRC tumor tissues, relative to adjacent normal tissues, is significantly associated with a poorer patient prognosis. Experimental data indicate that silencing NAT1 in CaCO2 and HCT116 cell lines results in heightened resistance to five chemotherapeutic agents: vinblastine, docetaxel, gemcitabine, vincristine, and daporinad. Additionally, NAT1 silencing increases the proportion of LGR5&lt;sup&gt;+&lt;/sup&gt; cells, which are known to be chemo-resistant. Our research further revealed that exposure to these five drugs induces a decrease in NAT1 expression within CRC cells. Mechanistic insights show that NAT1 knockdown triggers a metabolic reprogramming in CRC cells, shifting from oxidative phosphorylation and the tricarboxylic acid cycle to a preference for glycolysis. Furthermore, silencing of NAT1 in CRC cells leads to an up-regulation of VEGFA expression. Notably, the application of anti-PD-1 therapy was demonstrated to significantly disrupt the VEGFA-VEGFR axis signaling, an interaction critical between CRC cells and endothelial cells. This discovery underscores the potential of targeting the VEGFA pathway as a therapeutic approach to mitigate the adverse effects associated with NAT1 down-regulation in CRC.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Conclusion: &lt;/strong&gt;Our study underscores the multif","PeriodicalId":10366,"journal":{"name":"Clinical Epigenetics","volume":"17 1","pages":"77"},"PeriodicalIF":4.8,"publicationDate":"2025-05-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12053866/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143984281","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Recent advances on gene-related DNA methylation in cancer diagnosis, prognosis, and treatment: a clinical perspective.","authors":"Alessandro Lavoro, Daria Ricci, Giuseppe Gattuso, Federica Longo, Graziana Spoto, Anastasia Cristina Venera Vitale, Maria Chiara Giuliana, Luca Falzone, Massimo Libra, Saverio Candido","doi":"10.1186/s13148-025-01884-2","DOIUrl":"https://doi.org/10.1186/s13148-025-01884-2","url":null,"abstract":"<p><p>Recent advances in screening programs and the development of innovative therapeutic strategies have significantly improved the clinical outcomes of cancer patients. However, many patients still experience treatment failure, primarily due to inherent or acquired drug resistance mechanisms. This challenge underscores the urgent need for novel therapeutic targets for the effective treatment of malignancies, as well as cancer-specific biomarkers to enhance early diagnosis and guide interventions. Epigenetic mechanisms, including DNA methylation, have recently garnered growing interest as key regulators of gene expression under both physiological and pathological conditions. Although epigenetic dysregulations are reliable tumor hallmarks, DNA methylation is still not routinely integrated into clinical practice, highlighting the need for further research to translate preclinical findings from the bench to the bedside. On these bases, the present review aims to illustrate the state of the art regarding the role of DNA methylation in cancer, describing the technologies currently available for DNA methylation profiling. Furthermore, the latest evidence on the application of DNA methylation hotspots in cancer diagnosis and prognosis, as well as the impact of epidrugs in cancer care, is discussed to provide a comprehensive overview of the potential clinical relevance of DNA methylation in advancing personalized medicine.</p>","PeriodicalId":10366,"journal":{"name":"Clinical Epigenetics","volume":"17 1","pages":"76"},"PeriodicalIF":4.8,"publicationDate":"2025-05-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12054201/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143988700","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Causal associations between epigenetic age and thromboembolism: a bi-directional two-sample Mendelian randomization study.","authors":"Bowen Jin, Yunyan Li, Dingyang Li, Chi Jing, Qunshan Sheng","doi":"10.1186/s13148-025-01875-3","DOIUrl":"https://doi.org/10.1186/s13148-025-01875-3","url":null,"abstract":"<p><strong>Background: </strong>Thromboembolism is one of the most prevalent cardiovascular conditions affecting the elder population. The associations between epigenetic aging and thromboembolism risks remain incompletely elucidated. Through Mendelian randomization (MR), this research seeks to assess the causal links between genetically determined epigenetic aging factors and thromboembolism.</p><p><strong>Results: </strong>Genetic variants were extracted from genome-wide association studies (GWAS) under stringent threshold as instrumental variables (IVs). Bi-directional two-sample MR analyses were conducted to determine the direction of causal associations. We employed the inverse variance weighted (IVW), weighted median, weighted mode and MR Egger to estimate the causal effect, with sensitivity analyses such as Cochran's Q tests, MR-PRESSO and leave-one-out performed to avoid potential heterogeneity and pleiotropy. Our MR analysis revealed a causal association between intrinsic epigenetic age acceleration and deep vein thrombosis of lower extremities (IVW: OR 0.963, 95% CI 0.934-0.992, P = 0.014), and between the genetically determined levels of plasminogen activator inhibitor-1 and other arterial embolism and thrombosis (IVW: OR 1.000, 95% CI 1.000-1.0005, P = 0.029). Causality was also identified between the genetically predicted levels of FGF23 and other arterial embolism and thrombosis (IVW: OR: 1.661, 95% CI 1.051-2.624, P = 0.029) and arterial embolism and thrombosis of lower extremity artery (IVW: OR 1.68, 95% CI 1.031-2.725, P = 0.037). Moreover, bi-directional MR showed reverse effects between portal vein thrombosis and PhenoAge (IVW: OR 0.871, 95% CI 0.765-0.992, P = 0.037) and between venous thromboembolism and GrimAge (IVW: OR 1.186, 95% CI 1.048-1.341, P = 0.007). Sensitivity analysis using Cochran's Q tests, MR-PRESSO and leave-one-out excluded the influence of heterogeneity, horizontal pleiotropy, and outliers.</p><p><strong>Conclusion: </strong>Our results identified a causal association between genetically predicted epigenetic aging factors and thromboembolism. The findings highlight the necessity for further exploration into the underlying etiology of thromboembolism.</p>","PeriodicalId":10366,"journal":{"name":"Clinical Epigenetics","volume":"17 1","pages":"75"},"PeriodicalIF":4.8,"publicationDate":"2025-05-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12051321/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143969108","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Venetoclax confers synthetic lethality to chidamide in preclinical models with transformed follicular lymphoma.","authors":"Mengya Zhong, Guangchao Pan, Jinshui Tan, Jingwei Yao, Yating Liu, Jiewen Huang, Yuelong Jiang, Depeng Zhu, Jintao Zhao, Bing Xu, Jie Zha","doi":"10.1186/s13148-025-01878-0","DOIUrl":"https://doi.org/10.1186/s13148-025-01878-0","url":null,"abstract":"<p><p>Transformed follicular lymphoma (t-FL) is an aggressive and heterogeneous hematological malignancy with limited treatment success; the development of novel therapeutic approaches is urgently needed for patients with t-FL. Here, we conducted high-throughput screening (HTS) and in vitro experiments using t-FL cell lines and primary samples to assess the synergistic effects of the histone deacetylase inhibitor chidamide and the BCL-2 inhibitor venetoclax. In vivo efficacy was further tested in xenograft models. The combination of venetoclax and chidamide significantly inhibited cell proliferation, induced apoptosis, and arrested the cell cycle in the G0/G1 phase across multiple t-FL cell lines. Furthermore, the combined therapy effectively reduced tumor burden, extended overall survival in xenograft models, and synergistically targeted patient samples, while sparing normal PBMCs. Mechanistically, this combination disrupted mitochondrial membrane potential and modulated the Wnt signaling pathway, as evidenced by decreased protein expression levels of Wnt3a, Wnt5a/b, β-catenin, and phosphorylated GSK3β. Concurrently, the combined regimen enhanced their respective anticancer effects by inhibiting the key genes HDAC10 and BCL-xL. Taken together, venetoclax combined with chidamide presents a potent anticancer strategy in preclinical models of t-FL and merits further exploration in clinical trials to validate its effectiveness and safety for treating t-FL.</p>","PeriodicalId":10366,"journal":{"name":"Clinical Epigenetics","volume":"17 1","pages":"74"},"PeriodicalIF":4.8,"publicationDate":"2025-05-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12051286/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143981765","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Posttranscriptional RNA stabilization of telomeric RNAs FRG2, DBE-T, D4Z4 at human 4q35 in response to genotoxic stress and D4Z4 macrosatellite repeat length.","authors":"Valentina Salsi, Francesca Losi, Monica Salani, Paul D Kaufman, Rossella Tupler","doi":"10.1186/s13148-025-01881-5","DOIUrl":"https://doi.org/10.1186/s13148-025-01881-5","url":null,"abstract":"<p><strong>Background: </strong>Reduced copy number of the D4Z4 macrosatellite at human chromosome 4q35 is associated with facioscapulohumeral muscular dystrophy (FSHD). A pervasive idea is that chromatin alterations at the 4q35 locus following D4Z4 repeat unit deletion lead to disease via inappropriate expression of nearby genes. Here, we sought to analyze transcription and chromatin characteristics at specific regions of 4q35 and how these are affected by D4Z4 deletions and exogenous stresses.</p><p><strong>Results: </strong>We found that the 4q subtelomere is subdivided into discrete domains, each with characteristic chromatin features associated with distinct gene expression profiles. Centromeric genes within 4q35 (SLC25A4, FAT1 and FRG1) display active histone marks at their promoters. In contrast, poised or repressed markings are present at telomeric loci including FRG2, DBE-T and D4Z4. We discovered that these discrete domains undergo region-specific chromatin changes upon treatment with chromatin enzyme inhibitors or genotoxic drugs. We demonstrated that the 4q35 telomeric FRG2, DBE-T and D4Z4-derived transcripts are induced upon DNA damage to levels inversely correlated with the D4Z4 repeat number, are stabilized through posttranscriptional mechanisms upon DNA damage and are bound to chromatin.</p><p><strong>Conclusion: </strong>Our study reveals unforeseen biochemical features of RNAs from clustered transcription units within the 4q35 subtelomere. Specifically, the FRG2, DBE-T and D4Z4-derived transcripts are chromatin-associated and are stabilized posttranscriptionally after induction by genotoxic stress. Remarkably, the extent of this response is modulated by the copy number of the D4Z4 repeats, raising new hypotheses about their regulation and function in human biology and disease.</p>","PeriodicalId":10366,"journal":{"name":"Clinical Epigenetics","volume":"17 1","pages":"73"},"PeriodicalIF":4.8,"publicationDate":"2025-05-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12049803/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143987729","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"DNA methylation in primary myelofibrosis is partly associated with driver mutations and distinct from other myeloid malignancies.","authors":"Esra Dursun Torlak, Vithurithra Tharmapalan, Kim Kricheldorf, Joelle Schifflers, Madeline Caduc, Martin Zenke, Steffen Koschmieder, Wolfgang Wagner","doi":"10.1186/s13148-025-01877-1","DOIUrl":"https://doi.org/10.1186/s13148-025-01877-1","url":null,"abstract":"<p><strong>Background: </strong>Primary myelofibrosis (PMF) is a clonal blood disorder characterized by mutually exclusive driver mutations in JAK2, CALR, or MPL genes. So far, it is largely unclear if the driver mutations have a specific impact on DNA methylation (DNAm) profiles and how epigenetic alterations in PMF are related to other myeloid malignancies.</p><p><strong>Results: </strong>When we compared DNAm profiles from PMF patients we found very similar epigenetic modifications in JAK2 and CALR mutated cases, whereas MPL mutations displayed less pronounced and distinct patterns. Furthermore, induced pluripotent stem cell (iPSC) models with JAK2 mutations indicated only a moderate association with PMF-related epigenetic changes, suggesting that these alterations may not be directly driven by the mutations themselves. Additionally, PMF-associated epigenetic changes showed minimal correlation with allele burden and seemed to be largely influenced by shifts in the cellular composition. PMF DNAm profiles compared with those from other myeloid malignancies-such as acute myeloid leukemia, juvenile myelomonocytic leukemia, and myelodysplastic syndrome-showed numerous overlapping changes, making it difficult to distinguish PMF based on individual CpGs. However, a PMF score created by combining five CpGs was able to discern PMF from other diseases.</p><p><strong>Conclusion: </strong>These findings demonstrate that PMF driver mutations do not directly evoke epigenetic changes. While PMF shares epigenetic alterations with other myeloid malignancies, DNA methylation patterns can distinguish between PMF and related diseases.</p>","PeriodicalId":10366,"journal":{"name":"Clinical Epigenetics","volume":"17 1","pages":"72"},"PeriodicalIF":4.8,"publicationDate":"2025-05-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12048995/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143989705","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Maternal uniparental disomy of chromosome 7: how chromosome 7-encoded imprinted genes contribute to the Silver-Russell phenotype.","authors":"Matthias Begemann, Anna Lengyel, Eva Pinti, Árpád Ferenc Kovács, György Fekete, Svea Stratmann, Jeremias Krause, Miriam Elbracht, Florian Kraft, Thomas Eggermann","doi":"10.1186/s13148-025-01867-3","DOIUrl":"https://doi.org/10.1186/s13148-025-01867-3","url":null,"abstract":"<p><strong>Background: </strong>Silver-Russell syndrome (SRS) is a rare congenital growth disorder which is associated with molecular alterations affecting imprinted regions on chromosome 11p15 and maternal uniparental disomy of chromosome 7 (upd(7)mat). In 11p15, imprinted regions contributing to the SRS phenotype could be identified, whereas on chromosome 7 at least two regions in 7q32 and 7p13 are in discussion as SRS candidate regions. We report on DNA and RNA data from upd(7)mat patients and a monozygotic twin pair with a postnatal SRS phenotype carrying a small intragenic deletion within GRB10 to delineate the contribution of upd(7)mat and imprinted genes on this chromosome to the SRS phenotype.</p><p><strong>Results: </strong>Genome sequencing in the monozygotic twins revealed a 18 kb deletion within the paternal allele of the GRB10 gene. Expression of GRB10 in blood of the twins as well as in cells from upd(7)mat and upd(7q)mat patients was not altered, whereas RNAseq indicates noticeable changes of the expression of other genes encoded by chromosomes 7 and other genomic regions.</p><p><strong>Conclusions: </strong>Our data indicate that intrauterine growth restriction as the prenatal phenotype of upd(7)mat is caused by defective paternal alleles of the 7q32 region, as well as by overexpression of the maternal GRB10 allele whereas a defective GRB10 paternal allele does not cause this feature. The altered expression of MEST in 7q32 by upd(7)mat is associated with the complete SRS phenotype, whereas maternalization or deletion of the paternal GRB10 copy and duplication of the chromosomal region 7p12 are associated with a postnatal SRS-like phenotype.</p>","PeriodicalId":10366,"journal":{"name":"Clinical Epigenetics","volume":"17 1","pages":"70"},"PeriodicalIF":4.8,"publicationDate":"2025-04-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12042466/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143977311","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"DNA methylation in melanoma immunotherapy: mechanisms and therapeutic opportunities.","authors":"Maya G Deshmukh, Veronica T Brooks, Simon F Roy, Simon Milette, Marcus Bosenberg, Goran Micevic","doi":"10.1186/s13148-025-01865-5","DOIUrl":"https://doi.org/10.1186/s13148-025-01865-5","url":null,"abstract":"<p><p>Abnormal DNA methylation is a hallmark of cancer and a nearly universal feature of melanoma. DNA methylation plays well-appreciated melanoma cell-intrinsic roles, including silencing tumor-suppressor genes, regulating genomic stability, deregulating expression of oncogenes to potentiate proliferative signaling and tumor migration. With the recent success of immunological therapies for melanoma, important roles for DNA methylation are also emerging at the interface between melanoma and immune cells with the potential to regulate the anti-tumor immune response. These newly recognized roles for DNA methylation in controlling melanoma cell immunogenicity, expression of MHC and immune checkpoint molecules as well as T cell phenotypes in the tumor microenvironment raise the possibility of using DNA methylation to develop improved therapies and methylation-based biomarkers. In addition to reviewing the \"immune dimension\" of DNA methylation, we summarize recent developments with potential clinical applications in melanoma, such as targeted DNA methylation editing, single-cell methylation approaches, and measurement of circulating methylated DNA. An improved understanding of the immune roles of DNA methylation presents an exciting opportunity for continued improvement of care and outcomes for patients with melanoma.</p>","PeriodicalId":10366,"journal":{"name":"Clinical Epigenetics","volume":"17 1","pages":"71"},"PeriodicalIF":4.8,"publicationDate":"2025-04-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12044936/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143956223","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}