Clinical Epigenetics最新文献

{"title":"HRR gene promoter methylation-guided nomogram predicts PARP inhibitor efficacy and progression-free survival in high-grade serous ovarian cancer.","authors":"Zhihua Zhou, Baoqin Ge, Tingting Chen, Shizhen Shen, Nalan Tu, Yuanming Shen","doi":"10.1186/s13148-026-02159-0","DOIUrl":"10.1186/s13148-026-02159-0","url":null,"abstract":"<p><strong>Background: </strong>High-grade serous ovarian cancer (HGSOC) remains a lethal gynecologic malignancy with limited tools for accurately predicting PARP inhibitor (PARPi) efficacy. While promoter methylation of homologous recombination repair (HRR) genes is a potential biomarker, its clinical utility remains underexplored. This study aimed to systematically evaluate HRR gene promoter methylation profiles to predict PARPi sensitivity in HGSOC patients.</p><p><strong>Methods: </strong>We conducted a retrospective analysis of 96 HGSOC patients receiving PARPi maintenance therapy (olaparib or niraparib). The promoter methylation status of 12 HRR genes was quantitatively assessed via pyrosequencing. Patients were stratified into PARPi-sensitive and -insensitive groups based on OReO/ENGOT-ov38 criteria. Differential methylation sites were identified, lasso and multivariate logistic regression identified key methylation sites to construct a nomogram and a PARPi Resistance Score (PRS). PFS was analyzed by Kaplan‑Meier and Cox regression.</p><p><strong>Results: </strong>The PARPi-insensitive group exhibited significantly higher median methylation levels across HRR gene promoters compared to the sensitive group. Through rigorous screening, 12 CpG sites were consistently associated with PARPi response across subgroups. Through screening and LASSO regression, five CpG sites-ATM_Pos1, BRCA1(2S)_Pos2, BRCA2(1S)_Pos1, BRCA2(1S)_Pos7, and RAD51D_Pos6-were identified as independent predictors of PARPi sensitivity. The logistic model based on these five sites showed good discrimination, with area under the ROC curve (AUC) of 0.847 in the training set and 0.903 in the validation set; calibration and decision curve analysis supported clinical utility. Using the optimal PRS cutoff of - 1.023, High-PRS patients had significantly shorter median PFS (14 months vs. not reached; log‑rank P < 0.0001) and lower 12‑month PFS rate (52% vs. 97.2%). Multivariate Cox analysis confirmed PRS as the only independent prognostic factor for PFS (HR 4.85, 95% CI 2.31-10.20, P < 0.001).</p><p><strong>Conclusion: </strong>HRR gene promoter methylation, particularly at specific BRCA1, BRCA2 and RAD51D CpG sites, robustly predicts PARPi sensitivity and independently stratifies PFS in HGSOC patients. The nomogram and PRS provide clinically actionable tools for individualized PARPi therapy.</p>","PeriodicalId":10366,"journal":{"name":"Clinical Epigenetics","volume":" ","pages":""},"PeriodicalIF":4.4,"publicationDate":"2026-05-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13361930/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147971020","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-based estimator of blood telomere length (DNAmTL) outperforms qPCR-based telomere length in reflecting clinical and sociodemographic factors in people with HIV infection.","authors":"Andrés Esteban-Cantos, Javier Rodríguez-Centeno, Rocío Montejano, Julen Cadiñanos, Rosa de Miguel-Buckley, Lucía Gutiérrez-García, Cristina Marcelo-Calvo, Patricia Martínez-Martín, Jose I Bernardino, Alejandro de Gea-Grela, Alejandro Díez-Vidal, Carlos Oñoro, Berta Rodés, José R Arribas","doi":"10.1186/s13148-026-02164-3","DOIUrl":"10.1186/s13148-026-02164-3","url":null,"abstract":"<p><strong>Background: </strong>Telomere length (TL) is a widely used biomarker of biological aging, and is shortened in people living with HIV (PWH) due to chronic inflammation and immune-activation. The DNA methylation-based estimator of TL (DNAmTL) has emerged as a promising alternative to classical TL measurements, but their comparative performance in PWH remains poorly characterized.</p><p><strong>Methods: </strong>We conducted a cross-sectional study comparing DNAmTL and monochrome multiplex quantitative PCR-based TL (qPCR-TL) in two cohorts of PWH: 160 ART-naïve individuals and 143 long-term treated individuals with sustained viral suppression. DNAmTL was derived from blood DNA methylation profiles generated using the Infinium MethylationEPIC arrays, while qPCR-TL was measured using a standardized assay. We evaluated the agreement between methods using correlation, Bland-Altman analysis and Cohen's Kappa coefficient, and their associations with demographic, clinical and immunological factors were assessed using multivariable linear regression.</p><p><strong>Results: </strong>DNAmTL and qPCR-TL were moderately correlated in both ART-naïve (r = 0.54, p < 0.001) and ART-treated participants (r = 0.46, p < 0.001), showing reasonable to fair agreement across continuous and categorical assessments. Both measures were inversely correlated with chronological age, although associations were stronger for DNAmTL. Compared to qPCR-TL, DNAmTL demonstrated more robust and independent associations with female sex and ethnicity, immunovirological markers of HIV disease severity such as plasma HIV-RNA viral load and the CD4:CD8 ratio, as well as with comorbidities including type 2 diabetes and hepatitis C virus coinfection.</p><p><strong>Conclusions: </strong>DNAmTL provides a more biologically informative measure of aging and disease burden in PWH. Further research is warranted to validate these results and to determine its predictive value for clinical outcomes.</p>","PeriodicalId":10366,"journal":{"name":"Clinical Epigenetics","volume":" ","pages":""},"PeriodicalIF":4.4,"publicationDate":"2026-05-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13361718/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147971022","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":"NRSF regulation of OPRM1 through histone acetylation.","authors":"Ryan Thompson, Christina Chan","doi":"10.1186/s13148-026-02146-5","DOIUrl":"10.1186/s13148-026-02146-5","url":null,"abstract":"<p><p>The Neuron Restrictive Silencer Factor (NRSF) is a master transcriptional regulator of neuronal differentiation. Dysregulation of NRSF in neurons contributes to multiple neurological disorder. Following peripheral nerve injury, NRSF is upregulated and has been implicated in the establishment and maintenance of neuropathic pain. While the molecular and genetic changes in nerves occur during neuropathic pain are numerous and complex, a key downstream consequence of NRSF activation is repression of the mu-opioid receptor gene (OPRM1), a critical mediator of nociception and opioid responsiveness. NRSF controls repression of gene expression through recruitment of histone deacetylases (HDACs) to target genes. Here, we demonstrate that pharmacological inhibition of HDACs with valproic acid (VPA) is able to de-repress expression of OPRM1 in iPSC-derived neurons. To produce more targeted epigenetic changes to specific genomic loci, we further employed a CRISPR based epigenetic editing strategy using dCas9 fused to the histone acetyltransferase p300. Targeted acetylation of the OPRM1 gene promoter region with dCas9-p300 upregulated OPRM1 gene expression. Restoring OPRM1 expression in neurons is able to alter its responsiveness to mu-opioid receptor agonist, as evidenced by changes in calcium signaling. This study demonstrated targeted epigenetic acetylation with dCas9-p300 is a powerful strategy to reverse NRSF-medicated gene repression and restore opioid receptor function, highlighting a potential therapeutic avenue for neuropathic pain.</p>","PeriodicalId":10366,"journal":{"name":"Clinical Epigenetics","volume":" ","pages":""},"PeriodicalIF":4.4,"publicationDate":"2026-05-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13366922/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147971027","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":"Development, characterization, and inter-laboratory validation of methylated human cell free DNA candidate reference materials.","authors":"Zhiyong He, Yves Konigshofer, Russell Garlick, Jayanthi Ramprakash, Madhumita Ramesh, Eric Hall, Adam Corner, Michelle Clarissa, Jocelyn H Wright, Victoria K Cannon, Ming Yu, William M Grady, Cecilia C S Yeung, Zachary Heimer, Zhili Wang, ShiPing Zou, Shidong Jia, Fang Liu, Giancarlo Bonora, Karol Bomsztyk, Daniel Mar, Kenneth D Cole, Hua-Jun He","doi":"10.1186/s13148-026-02156-3","DOIUrl":"10.1186/s13148-026-02156-3","url":null,"abstract":"<p><strong>Background: </strong>Aberrant DNA methylation biomarkers have demonstrated potential for early cancer detection, multicancer detection, and determining the tissue of origin. Due to their stability, frequency, and accessibility in bodily fluids, circulating cell-free DNA (cfDNA) methylation is a promising biomarker in liquid biopsy. A reliable and quantifiable analysis of cfDNA methylation status is critical to its application. However, there are current challenges and a lack of consensus on measurement methods. To address this, we developed two candidate methylated cfDNA reference materials (RMs).</p><p><strong>Methods: </strong>The National Institute of Standards and Technology (NIST) RM consists of five components, formulated by mixing in vitro methylated cfDNA simulant at fractions of 0%, 5%, 25%, 50%, and 100% with native-state cfDNA simulant derived from the GM24385 cell line. The LGC Clinical Diagnostics (LGC) RM consists of two components: non-methylated cfDNA simulant derived from GM24385 genomic DNA and whole genome amplification and methylated cfDNA produced by in vitro methylation of amplified material. The candidate RMs were characterized, and the methylation status of three targets was confirmed by droplet digital PCR (ddPCR) assays. To test the utility of these RMs, six laboratories participated in an interlaboratory study, each using their own lab-developed assays and methods, which included methylation-specific qPCR, nanoplate digital PCR (dPCR), ddPCR, matrix methylated DNA immunoprecipitation-based assays, and whole-genome bisulfite sequencing.</p><p><strong>Results: </strong>The interlaboratory study results showed that the designed percentage of methylation was well correlated with the observed values across all participating labs, and good reproducibility was found for each individual method. However, slightly different methylation proportions associated with assay-specific biases were observed.</p><p><strong>Conclusions: </strong>This study clearly demonstrates the value of candidate RMs as standards for evaluating assay performance, as well as for increasing confidence in reporting cfDNA methylation status for clinical applications.</p>","PeriodicalId":10366,"journal":{"name":"Clinical Epigenetics","volume":" ","pages":""},"PeriodicalIF":4.4,"publicationDate":"2026-05-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13352979/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147971067","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":"Genomic characterization of uterine adenomatoid tumors reveals recurrent alterations in KMT5A and KMT2C.","authors":"Shufeng Kang, Fangfang Xu, Juan Tao, Guofang Chen, Shuangdi Li","doi":"10.1186/s13148-026-02161-6","DOIUrl":"10.1186/s13148-026-02161-6","url":null,"abstract":"<p><strong>Background: </strong>Uterine adenomatoid tumors (UATs) are rare benign mesothelial neoplasms with poorly characterized molecular features. Comprehensive genomic profiling of UATs remains limited.</p><p><strong>Methods: </strong>Targeted sequencing of 20 pathologically confirmed UATs was performed using a 641-gene panel. Immunohistochemical (IHC) analyses were conducted to assess protein expression patterns. Functional assays were performed in the Ishikawa endometrial carcinoma cell line to provide preliminary insight into the potential biological impact of KMT5A knockdown. Publicly available datasets (TCGA and cBioPortal) were analyzed to place these alterations into a broader molecular context across gynecologic malignancies.</p><p><strong>Results: </strong>Recurrent mutations in KMT5A and KMT2C were identified in all cases (20/20, 100%), with consistent co-occurrence across the cohort. Additional alterations were observed in HLA-B (65%), HLA-A (50%), ROS1 (45%), TRAF7 (45%), SDHA (30%), and KMT2A (30%). IHC analysis demonstrated higher expression of TRAF7, γ-H2AX, CALB2, and Ki-67 in tumors with elevated KMT5A expression. KMT5A knockdown in Ishikawa cells reduced proliferative and migratory capacity. Comparative analyses indicated that KMT5A mutations are uncommon in gynecologic malignancies (< 3%), whereas KMT2C alterations are more broadly distributed.</p><p><strong>Conclusions: </strong>UATs exhibit a distinctive mutational profile characterized by recurrent KMT5A and KMT2C co-mutations. These findings provide a comprehensive molecular characterization of UATs and suggest that recurrent alterations in chromatin-regulatory genes may represent characteristic genomic features that warrant further investigation.</p>","PeriodicalId":10366,"journal":{"name":"Clinical Epigenetics","volume":" ","pages":""},"PeriodicalIF":4.4,"publicationDate":"2026-05-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13348700/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147962364","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":"Sperm tRNA-derived fragments: molecular mechanisms and clinical implications for paternal epigenetic inheritance.","authors":"Shiwei Song, Bin Zhang, Fengli Xiong, Mengkun Li, Lingqi Liu, DongDong Meng, Changfeng Yang, Fulin Ma, Haizhong Xu, Dehui Chang","doi":"10.1186/s13148-026-02155-4","DOIUrl":"10.1186/s13148-026-02155-4","url":null,"abstract":"<p><p>Sperm tRNA-derived fragments (tRFs) have emerged as novel regulators of paternal epigenetic inheritance. By modulating embryonic epigenetic reprogramming, transposon silencing, and intergenerational genetic programming, tRFs mediate the transgenerational transmission of paternal environmental information, extending conventional notions of genetic inheritance. This review systematically elaborates the molecular mechanisms, clinical applications, and potential interventional strategies of tRFs. Through an in-depth analysis of how tRFs regulate the epigenetic landscape during embryonic development, we highlight their applications in diagnosing and treating male infertility, as well as in preventing transgenerational diseases. This work provides new insights into interventions targeting paternal epigenetic transmission and associated disorders.</p>","PeriodicalId":10366,"journal":{"name":"Clinical Epigenetics","volume":" ","pages":""},"PeriodicalIF":4.4,"publicationDate":"2026-05-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13445796/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147940399","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":"KIT-dependent acute myeloid leukemias are responsive to LSD1 inhibition.","authors":"Amal Kamal Abdel-Aziz, Mona Kamal Saadeldin","doi":"10.1186/s13148-026-02098-w","DOIUrl":"10.1186/s13148-026-02098-w","url":null,"abstract":"<p><p>Lysine specific demethylase 1 (LSD1 or KDM1A) is a FAD-dependent histone demethylase which is overexpressed in acute myeloid leukemias (AMLs). Indeed, several selective LSD1 inhibitors (LSD1is) are currently evaluated in clinical trials. We previously demonstrated that the mammalian target of rapamycin (mTOR) signalling is inhibited in LSD1i-sensitive AMLs and is activated in LSD1i-partially responsive/tolerant AMLs following LSD1i. Herein, we sought to systematically decipher the molecular basis underlying the responsiveness of AML cells to LSD1is. Genome-wide transcriptomic profiling, RT-qPCR and immunoblot analyses revealed that stem cell factor tyrosine kinase receptor (KIT) is preferentially overexpressed in LSD1i-sensitive AMLs compared to LSD1i-partially responsive/tolerant AMLs. Pharmacological and genetic interference with LSD1 repressed KIT transcription. c-Kit acted upstream of ERK/mTOR signalling. Chromatin immunoprecipitation studies revealed that LSD1 binds in proximity to KIT TSS and modulates repressive H3K9me2 marks. Inhibiting c-Kit augmented the anti-leukemic activity of LSD1is in KIT-dependent AML cells. Consistently, KIT mRNA positively correlated with LSD1 transcript levels in primary human AML biospecimens and pharmacological LSD1i repressed KIT transcription in primary human AML samples ex vivo. Collectively, this study sheds light on the epigenetic modulation of KIT transcription by LSD1 and underscores the therapeutic potential of co-targeting LSD1/KIT in KIT-dependent AMLs.</p>","PeriodicalId":10366,"journal":{"name":"Clinical Epigenetics","volume":" ","pages":""},"PeriodicalIF":4.4,"publicationDate":"2026-05-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13173958/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147927184","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":"Identification of METTL3 and PRMT5 as an oncogenic pair for the prognosis and therapeutic targets of colorectal cancer subtype.","authors":"Qian Zhao, Si Li, Aiwen Chen, Sheng Zhu, Jianrui Zhong, Pengwei Zhang, Yan-Ling She, Rui Chen, Wanting Liu, Yang Wang","doi":"10.1186/s13148-026-02144-7","DOIUrl":"10.1186/s13148-026-02144-7","url":null,"abstract":"<p><strong>Background: </strong>METTL3 is a pivotal N6-methyladenosine (m⁶A) regulator that is linked to a worse prognosis of colorectal cancer (CRC). However, METTL3's oncogenic molecular networks in CRC remain unclear. This study aims to establish a co-expression network of METTL3 and identify novel diagnostic and therapeutic targets for CRC.</p><p><strong>Methods: </strong>We integrated transcriptomic datasets with clinical cohorts and patient-derived organoids (PDOs) to evaluate the expression profiles of METTL3 and PRMT5. Mechanistic insights were gained through co-immunoprecipitation (Co-IP), m⁶A-methylated RNA immunoprecipitation (MeRIP), and Quantitative real-time PCR (qRT-PCR) assays. Single-cell and spatial transcriptomics were employed to resolve their spatial co-localization and cellular architecture. Furthermore, we performed patient stratification based on the METTL3/PRMT5 axis to characterize tumor microenvironment (TME) remodeling. The functional roles of these proteins in cell proliferation, mitochondrial fission, and mitophagy were validated in CRC cells and PDOs. Finally, the synergistic efficacy of the METTL3 inhibitor STM2457 and the PRMT5 inhibitor GSK591 was evaluated.</p><p><strong>Results: </strong>We identified a reciprocal positive feedback loop between METTL3 and PRMT5 that drives CRC malignancy: PRMT5 enhances METTL3 stability via symmetric dimethylarginine modification, while METTL3 facilitates PRMT5 expression in an m⁶A-dependent manner. Spatial and single-cell analysis revealed that their co-expression is spatially restricted and strongly correlates with an immunosuppressive TME. High METTL3/PRMT5 expression defines a specific molecular subtype characterized by accelerated cell cycle progression, DNA replication, and aberrant organelle fission. Critically, these phenotypes were functionally validated, showing that the METTL3/PRMT5 axis governs mitochondrial homeostasis. From a clinical perspective, CRC cell lines and PDOs with high METTL3/PRMT5 expression exhibited heightened sensitivity to combined inhibition with STM2457 and GSK591, revealing a potent therapeutic vulnerability.</p><p><strong>Conclusion: </strong>Our findings establish METTL3 and PRMT5 as a pair of robust biomarkers for patient stratification and highlight the synergistic targeting of m⁶A and protein methylation as a promising precision oncology strategy for CRC.</p>","PeriodicalId":10366,"journal":{"name":"Clinical Epigenetics","volume":" ","pages":""},"PeriodicalIF":4.4,"publicationDate":"2026-05-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13455430/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147927177","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":"Genome-wide DNA methylation signatures in blood associated with pediatric obesity.","authors":"Barbara Slapnik, Robert Šket, Blaž Vrhovšek, Primož Kotnik, Tadej Battelino, Jernej Kovač","doi":"10.1186/s13148-026-02153-6","DOIUrl":"10.1186/s13148-026-02153-6","url":null,"abstract":"<p><strong>Background: </strong>Pediatric obesity is the most prevalent nutritional disorder in children and adolescents and is associated with multiple comorbidities. Understanding epigenetic mechanisms, particularly DNA methylation, offers potential for early risk prediction, prevention, and personalized interventions. In this study, genome-wide DNA methylation profiles in blood from children with obesity and matched controls were compared using Oxford Nanopore Technologies. Two independent analytical tools were applied to identify differentially methylated regions. Clinical data included family history, weight, BMI, and age at first examination. Participants with monogenic obesity, identified via short-read whole-exome sequencing, were excluded.</p><p><strong>Results: </strong>The cohort included five girls and five boys with obesity (median age 14.33, IQR 1.65; median BMI SDS 3.42, IQR 0.55) and matched controls (median age 13.94, IQR 0.52; median BMI SDS 0.26, IQR 1.71). Seven consensus differentially methylated regions were consistently identified, overlapping genes involved in metabolism and obesity-related comorbidities. Hypermethylation was observed in PM20D1, PM20D1-AS1, AC119673.2 (26.05% ± 0.78%), and GM2A (33.60% ± 1.10%) in children with obesity, primarily affecting metabolic and adipogenic pathways. Hypomethylation was detected in genes linked to obesity and its comorbidities, including S100A14, S100A16 (- 25.4% ± 0.48%), SNTG2 (- 25.55% ± 0.18%), ADARB2, LINC00200 (- 21.35% ± 0.98%), LRRC32, AP001189.1 (- 27.25%), CBLN3 and KHNYN (- 23.20% ± 0.80%).</p><p><strong>Conclusions: </strong>Long-read genome-wide methylation profiling can detect obesity-associated epigenetic loci in children. Blood-based markers in genes regulating metabolism and obesity comorbidities could support early risk prediction, patient stratification, and targeted prevention. Extending this work to larger and more diverse cohorts will be necessary to evaluate the robustness of these results and their potential translational relevance.</p>","PeriodicalId":10366,"journal":{"name":"Clinical Epigenetics","volume":" ","pages":""},"PeriodicalIF":4.4,"publicationDate":"2026-05-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13343863/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147927206","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":"Harnessing archaeogenetic for cancer therapy: bridging ancient DNA insights with modern therapeutic innovations.","authors":"Sonakshi Antal, Sakthivel Sakthivel, Pawan Kumar Goswami, Dinesh Kumar, Suresh Babu Kondaveeti","doi":"10.1186/s13148-026-02157-2","DOIUrl":"10.1186/s13148-026-02157-2","url":null,"abstract":"<p><p>Cancer is not only a modern disease but an evolutionary condition shaped by long-term genetic and epigenetic changes. Research in archaeogenetics and ancient DNA (aDNA) provides new insights into how inherited mutations, viral elements, and environmental exposures have influenced cancer risk over thousands of years. This review explores how ancient genomic and epigenomic evidence contributes to understanding the origins of cancer and its relevance to modern clinical oncology. Evidence from skeletal and mummified remains confirms that malignancies existed long before industrialization. Ancient genomes reveal hereditary risk variants in cancer-related genes such as BRCA and TP53, suggesting that genetic susceptibility to cancer has deep evolutionary roots. Importantly, reconstructed DNA methylation patterns from ancient samples indicate that epigenetic regulation of tumor suppressor genes and oncogenic pathways has been conserved across time. Human endogenous retroviruses (HERVs), integrated into the human genome during evolution, show epigenetic activation in several cancers and may serve as potential biomarkers or therapeutic targets. Comparative analyses further demonstrate both stable mutational processes and environmentally influenced epigenetic shifts. Overall, integrating ancient epigenomic data with modern multi-omics approaches enhances our understanding of cancer biology. This evolutionary and epigenetic perspective may support biomarker discovery, improve risk stratification, and guide the development of targeted and immunotherapeutic strategies in precision oncology.</p>","PeriodicalId":10366,"journal":{"name":"Clinical Epigenetics","volume":" ","pages":""},"PeriodicalIF":4.4,"publicationDate":"2026-05-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13339689/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147873812","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}