Clinical Epigenetics最新文献

{"title":"Epigenomic subtypes and prognostic methylation signatures in clear cell renal cell carcinoma.","authors":"Laura Iisager, Cecilie Lindgaard, Johanne Ahrenfeldt, Jesper Jespersen, Karoline Kondrup, Laura Zanini, Anna K Keller, Line Raaby, Mie G Thorlund, Karina D Sørensen, Niels Fristrup, Iben Lyskjær","doi":"10.1186/s13148-026-02055-7","DOIUrl":"10.1186/s13148-026-02055-7","url":null,"abstract":"<p><strong>Background: </strong>Clear cell renal cell carcinoma (ccRCC) is characterized by marked epigenetic dysregulation, contributing to aberrant gene expression and tumor progression. To expand current knowledge on genome-wide methylation patterns in ccRCC, we performed Methylated DNA Immunoprecipitation sequencing (MeDIP-seq) on tumor samples from 116 ccRCC patients and 34 adjacent normal renal tissues. We identified differentially methylated regions (DMRs) and integrated these findings with genome-wide copy number alterations.</p><p><strong>Results: </strong>ccRCC tumors exhibited global hypomethylation combined with focal hypermethylation, particularly within intergenic and repetitive genomic regions. Unsupervised clustering revealed three distinct subtypes, including one subtype characterized by chromosomal instability, synchronous metastasis, and poor survival outcomes. We developed a novel methylation score (MethScore), based on hypermethylated regions, which strongly correlated with disease stage and independently predicted overall survival beyond age and clinical stage. Notably, high methylation levels of specific DMRs were linked to recurrence and advanced disease. Validation with TCGA Kidney Renal Clear Cell Carcinoma methylation data supported the prognostic value of these hypermethylated regions. Additionally, MeDIP-seq accurately detected critical copy number alterations, particularly chromosome 3p loss, which were found in 88% of tumors.</p><p><strong>Conclusions: </strong>Together, our findings demonstrate that genome-wide methylation profiling can resolve clinically relevant ccRCC subtypes, uncover novel biomarkers of disease aggressiveness, and improve patient risk stratification beyond current clinical models.</p>","PeriodicalId":10366,"journal":{"name":"Clinical Epigenetics","volume":" ","pages":"30"},"PeriodicalIF":4.4,"publicationDate":"2026-01-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12908367/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146028044","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":"HDAC11 interacts with the NuRD (MTA3) complex to transcriptionally suppress TGFβ1 expression and inhibit hepatocellular carcinoma metastasis.","authors":"Yang Yang, Jiaoli Wang, Qingqing Wu, Yishan Wang, Hui Meng, Lulu Zeng, Tian Qiu, Haixia Zhao, Qin Hu, Qiaoyou Weng, Meiling Liu, Minjiang Chen, Rongfang Qiu, Jiansong Ji, Weiqian Chen","doi":"10.1186/s13148-026-02050-y","DOIUrl":"10.1186/s13148-026-02050-y","url":null,"abstract":"<p><p>Hepatocellular carcinoma (HCC) is a leading global health concern, recognized for its complex pathogenesis and high mortality rates. The metastatic progression of HCC, considered the terminal event in tumor development, plays a pivotal role in determining patient prognosis, with metastasis being a key factor in poor survival outcomes.HDAC11 was found to be highly expressed in HCC tissues, with its elevated expression significantly correlating with poor patient survival. Both in vitro and in vivo experiments demonstrated that silencing HDAC11 led to a marked reduction in HCC cell proliferation. Interestingly, HDAC11 knockdown also resulted in a substantial increase in the metastatic potential of HCC cells. Mass spectrometry analysis revealed that HDAC11 interacts with the NuRD (MTA3) complex. Consistently, immunoprecipitation and GST pull-down assays demonstrated that the N-terminal region of HDAC11 directly binds to MTA3. Moreover, transcriptomic analysis indicated that HDAC11 represses TGFB1 transcription, thereby inhibiting HCC metastasis. The enhanced metastatic phenotype induced by HDAC11 silencing was reversed upon concurrent down-regulation of TGFB1. Moreover, nanoparticles encapsulating both HDAC11 and TGF-β1 inhibitors effectively suppressed HCC cell proliferation and metastasis. This research elucidates the molecular mechanism by which HDAC11 inhibits metastasis and provides an effective strategy to mitigate the side effects associated with HDAC11 inhibition, offering novel insights and approaches for the precision treatment of HCC.</p>","PeriodicalId":10366,"journal":{"name":"Clinical Epigenetics","volume":" ","pages":"29"},"PeriodicalIF":4.4,"publicationDate":"2026-01-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12895668/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145994480","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":"HIV associated epigenetic trends and chronic diseases: insights into the hidden burden of chronic infection.","authors":"Courtney G Wallace, Zachary Capriotti, Zachary Klase","doi":"10.1186/s13148-025-02045-1","DOIUrl":"10.1186/s13148-025-02045-1","url":null,"abstract":"<p><p>Human Immunodeficiency Virus (HIV) remains a major health challenge despite dramatic advances in treatment and prevention. People living with HIV (PLWH) continue to experience high rates of non-AIDS comorbidities, including cardiovascular, renal, pulmonary, oncologic, and neurocognitive disorders. These conditions persist under viral suppression, underscoring the lasting biological impact of infection. Epigenetic dysregulation has emerged as a key driver of these outcomes. HIV integration, viral proteins, chronic inflammation, and ART exposure have all been reported to alter DNA methylation, histone modifications, transcription factor networks, and non-coding RNA regulation. These changes extend beyond infected cells, reprogramming uninfected immune and tissue compartments. Long-lived cell populations display features of epigenetic aging contributing to chronic inflammation and multimorbidity. Epigenetic clocks consistently reveal accelerated biological aging in PLWH, linking infection to age-related disease risk. Overall, HIV should be viewed not only as a virologic condition but also as one of persistent epigenomic remodeling. Recognizing how durable reprogramming sustains inflammation, accelerates aging, and promotes comorbidity will be critical for advancing beyond viral suppression toward interventions that mitigate long-term health risks in PLWH.</p>","PeriodicalId":10366,"journal":{"name":"Clinical Epigenetics","volume":" ","pages":"28"},"PeriodicalIF":4.4,"publicationDate":"2026-01-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12892797/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145988247","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":"Diet intervention altered DNA methylation of potassium voltage-gated channel subfamily Q member 1 in metabolic dysfunction-associated steatohepatitis.","authors":"Xinyu Shi, Hualing Song, Xinying Xiong, Shuang Wei, Lei Zhang, Shengfu You, Wenjun Zhou, Guang Ji, Baocheng Liu, Na Wu","doi":"10.1186/s13148-025-01950-9","DOIUrl":"https://doi.org/10.1186/s13148-025-01950-9","url":null,"abstract":"<p><strong>Background: </strong>Lifestyle interventions are cornerstones of metabolic dysfunction-associated fatty liver disease (MASLD) management, and differential DNA methylation of potassium voltage-gated channel subfamily Q member 1 (KCNQ1) was involved in MASLD-related diseases. However, little is known about the DNA methylation mechanism of KCNQ1 underlying the effect of lifestyle interventions on the most common liver disease.</p><p><strong>Objective: </strong>This study aimed to investigate the role of DNA methylation of KCNQ1 in metabolic dysfunction-associated steatohepatitis (MASH) after diet intervention.</p><p><strong>Methods: </strong>This study utilized 38 male C57BL/6 mice (9-week-old, SPF grade). Following a 1-week acclimatization period, animals were randomly allocated to receive either a methionine-choline deficient (MCD, n = 23) or methionine-choline sufficient (MCS, n = 15) dietary regimen for 4 weeks. Seven mice per group were subsequently euthanized for MASH model validation. After confirming successful model establishment, remaining MASH mice underwent randomized allocation to four-week interventions: low-fat diet (LFD, n = 8), continued MCD feeding (n = 8), or control MCS maintenance (n = 8). Genomic DNA methylation patterns in hepatic and adipose tissues were analyzed using methylation-sensitive restriction enzyme sequencing (MethylRAD). For LFD-treated MASH specimens, EpiTYPER mass spectrometry and quantitative reverse transcription PCR were employed to assess DNA methylation status and transcriptional expression of KCNQ1, respectively.</p><p><strong>Results: </strong>Hypermethylation in the intron of KCNQ1 was observed after LFD intervention in the liver and adipose tissue of MASH mice (p < 0.05) with MethylRAD sequencing. High DNA methylation and low mRNA expression of KCNQ1 were validated in adipose tissue of MASH mice in response to LFD (p < 0.05) with the EpiTYPER array.</p><p><strong>Conclusions: </strong>The study reinforced the role of DNA methylation in regulating gene expression of KCNQ1 in response to LFD intervention and highlighted that the DNA methylation of KCNQ1 in MASH adipose tissue could be tissue-specific. All these results contribute to elucidating the molecular mechanisms underlying the activities of DNA methylation in MASH.</p>","PeriodicalId":10366,"journal":{"name":"Clinical Epigenetics","volume":" ","pages":""},"PeriodicalIF":4.4,"publicationDate":"2026-01-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145965294","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Smoking behaviour, altered DNA methylation, and heart failure risk: evidence from a prospective cohort and epigenetic Mendelian randomization study.","authors":"Zheng-Qi Song, Bo-Xiang Wang, Zhi-Bo Zhou, Sheng-Ke Wu, Yi-Han Sun, Yi-He Chen","doi":"10.1186/s13148-026-02048-6","DOIUrl":"10.1186/s13148-026-02048-6","url":null,"abstract":"<p><strong>Background: </strong>To date, there is still a lack of studies focusing on the interactions between tobacco smoking, epigenetic modifications, and heart failure (HF) risk.</p><p><strong>Methods: </strong>We first performed a prospective cohort study in the UK Biobank to assess the causal relationship between smoking behaviours and HF incidence. Subsequently, we applied two-sample Mendelian Randomization (MR) and epigenetic MR to further investigate the causal effects of smoking behaviours and related DNA methylation on HF, including its subtypes: heart failure with preserved ejection fraction (HFpEF) and heart failure with reduced ejection fraction (HFrEF).</p><p><strong>Results: </strong>In the UK Biobank cohort, former, ever, and current smoking were all associated with a higher risk of HF, with a clear dose-response relationship observed for pack-years of smoking. Additionally, earlier smoking cessation was linked to a lower risk of HF. Two-sample MR validated these observational findings and further identified the harmful effects of smoking behaviours on both HFpEF and HFrEF. In the epigenetic MR analysis, we found that DNA methylation alteration at cg15234271 [HPN] was associated with a reduced risk of HF, whereas cg16071219 [LPAR6], cg19593285 [E2F1], and cg01305745 [VKORC1] were linked to an elevated risk. For HF subtypes, cg26161820 [PPP1R1B] and cg26716839 [UNC119B] were associated with a lowered risk of HFrEF, while cg08548559 [PIK3IP1] was linked to an increased risk of HFpEF.</p><p><strong>Conclusion: </strong>Our study demonstrates associations between smoking behaviours, related DNA methylation, and HF incidence, offering novel insights into the pathogenesis of HF.</p>","PeriodicalId":10366,"journal":{"name":"Clinical Epigenetics","volume":" ","pages":"27"},"PeriodicalIF":4.4,"publicationDate":"2026-01-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12888249/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145965258","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":"Modeling mammalian meiosis with pluripotent stem cells: progress and challenges.","authors":"Feng Yang, Jiarui Gu, Haiying Chen, Yuying Wang, Wenqiong Huang, Xiaoli Chen, Meijun Liu, Xianqiang Yu, Kenneth Cp Cheung","doi":"10.1186/s13148-025-02044-2","DOIUrl":"10.1186/s13148-025-02044-2","url":null,"abstract":"<p><p>Meiosis is a specialized cell division producing haploid gametes from diploid germ cells and is vital to sexual reproduction in mammals. This process entails carefully regulated molecular events including double-strand break repair, remodeling of the chromatin and the segregation of the chromosomes. There have been significant advances in understanding the core mechanisms through genetics and imaging techniques. Nevertheless, studying human meiosis is still difficult owing to limited access to tissue and interspecies differences in models using animals. Pluripotent stem cells (PSCs), namely embryonic and induced pluripotent stem cells, have turned out to be new in vitro models to model early germ cell development and meiotic progress in recent times. This article outlines the molecular regulation of meiosis in mammals and discusses the way in which the use of PSC-based models has begun to supplement classical methodologies in the study of meiosis.</p>","PeriodicalId":10366,"journal":{"name":"Clinical Epigenetics","volume":" ","pages":"25"},"PeriodicalIF":4.4,"publicationDate":"2026-01-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12882288/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145942748","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":"Association between cardiovascular health and epigenetic aging: a twin study.","authors":"Hui Cao, Ziyun Jiang, Weihua Cao, Jun Lv, Canqing Yu, Tao Huang, Dianjianyi Sun, Chunxiao Liao, Yuanjie Pang, Runhua Hu, Ruqin Gao, Min Yu, Jinyi Zhou, Xianping Wu, Yu Liu, Wenjing Gao, Liming Li","doi":"10.1186/s13148-025-02034-4","DOIUrl":"10.1186/s13148-025-02034-4","url":null,"abstract":"<p><strong>Objective: </strong>To explore the association between life's essential 8 and epigenetic age based on twins population.</p><p><strong>Methods: </strong>This study included 1030 twins (515 pairs) for cross-sectional analysis and conducted cross-lagged analysis among 294 twins (147 pairs) who participated in both the baseline and follow-up surveys from the Chinese National Twin Registry. LE8 scores were obtained from measurements based on American Heart Association definitions. DNA methylation data were used to calculate epigenetic age metrics, including GrimAA, DamAA and DunedinPACE. Linear mixed-effect models were applied for cross-twin analyses and within-monozygotic-pair analyses.</p><p><strong>Results: </strong>In the cross-sectional analysis, higher LE8 score was associated with slower epigenetic aging (DunedinPACE and DamAA) in both across-twin analyses and within-monozygotic-pair analyses. In stratified analyses, the association between LE8 score and epigenetic age appeared more significant in males and in individuals aged 50 years older. The cross-lagged analysis further revealed significant temporal associations between LE8, health factor, and DunedinPACE.</p><p><strong>Conclusion: </strong>Higher LE8 scores were associated with a deceleration in biological aging.</p>","PeriodicalId":10366,"journal":{"name":"Clinical Epigenetics","volume":" ","pages":"23"},"PeriodicalIF":4.4,"publicationDate":"2026-01-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12870025/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145905605","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":"Nutritional status-dependent DNA methylation modifications on adipose tissue in systemic lupus erythematosus women following folic acid and vitamin B12 supplementation: a randomized double-blind placebo-controlled trial.","authors":"Jhulia C N L da Mota, Lucas M Carvalho, Leticia L Souza, Amanda A Ribeiro, Marcela A S Pinhel, Carla B Nonino, Alexandre Leme Godoy, Eduardo F Borba, Bidossessi Wilfried Hounkpe, Bruno Gualano, Carolina F Nicoletti","doi":"10.1186/s13148-025-02041-5","DOIUrl":"10.1186/s13148-025-02041-5","url":null,"abstract":"<p><strong>Background: </strong>DNA methylation plays an important role in systemic lupus erythematosus (SLE) pathogenesis by regulating immune cell function and disease progression. Dietary factors, particularly methyl-donor micronutrients such as folic acid and vitamin B12, may influence DNA methylation patterns and autoimmune responses. However, their specific effects in SLE, especially in adipose tissue that is a key modulator of systemic inflammation, remain unclear. Given the high prevalence of obesity in SLE and its impact on disease severity, understanding the interaction between nutritional status, epigenetics, and immune dysregulation is crucial. This study examines whether folic acid and vitamin B12 supplementation modulate adipose tissue DNA methylation in female SLE patients, considering their nutritional status, to uncover potential mechanisms influencing disease progression and therapeutic response. This is a randomized, double-blind, placebo-controlled trial with premenopausal women with inactive SLE, classified as normal weight (NW, n = 23) or excess body weight (EBW, n = 27). Participants received daily supplementation of folic acid (400 mcg) and vitamin B12 (2000 mcg) or placebo for 12 weeks. Phenotypic characteristics and adipose tissue DNA methylation profiles were assessed before and after intervention using the Illumina EPIC BeadChip platform.</p><p><strong>Results: </strong>Supplementation significantly increased serum folic acid and vitamin B12 levels in both groups (p < 0.05), with a greater rise observed in NW patients (p = 0.035). In the NW group, 120 differentially methylated CpG sites (DMCpGs) were identified post-intervention (74 hypermethylated and 46 hypomethylated sites). These genes were linked to autoimmunity, inflammatory metabolism, obesity, and metabolic health pathways. In contrast, no DMCpGs were detected in the EBW group, potentially due to obesity-related chronic inflammation or altered folic acid metabolism associated with excessive adipose tissue.</p><p><strong>Conclusion: </strong>Folic acid and vitamin B12 supplementation modulated DNA methylation in SLE depending on nutritional status. Epigenetic remodeling occurred exclusively in NW patients, whereas EBW patients showed no detectable changes. These findings suggest that obesity may create an \"epigenetic resistance\" to micronutrient interventions, highlighting the importance of precision nutrition strategies in autoimmune disease management.</p><p><strong>Trial registration: </strong>NCT05097365.</p>","PeriodicalId":10366,"journal":{"name":"Clinical Epigenetics","volume":" ","pages":"21"},"PeriodicalIF":4.4,"publicationDate":"2026-01-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12866419/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145896463","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 patterns for indicators of liver steatosis: a longitudinal multiomic study.","authors":"Jo Ciantar, Sonja Rajić, Daria Kostiniuk, Ella Raulamo, Noora Kartiosuo, Liye Lai, Pashupati P Mishra, Leo-Pekka Lyytikäinen, Marcus E Kleber, Suvi Rovio, Juha Mykkänen, Katja Pahkala, Annette Peters, Juliane Winkelmann, Winfried März, Mika Kähönen, Olli Raitakari, Terho Lehtimäki, Melanie Waldenberger, Saara Marttila, Emma Raitoharju","doi":"10.1186/s13148-025-02037-1","DOIUrl":"10.1186/s13148-025-02037-1","url":null,"abstract":"<p><strong>Background: </strong>To identify blood DNA methylation profiles related to liver steatosis, we performed an EWAS on the presence of ultrasonically-identified liver steatosis in the Young Finns Study (YFS) participants (n = 1529, 33-50y.), and on liver enzyme levels and fatty liver index (FLI) across three discovery cohorts: YFS, LURIC (n = 2371, 17-92y.) and KORA FF4 (n = 1872, 39-88y.). We further investigated the discovered associations across the longitudinal subset of YFS (n = 255), encompassing three follow-ups over 32 years, and the three-generational YFS-3G follow-up in 2018-2020. Finally, we examined the associations of the discovered CpGs with nearby genetic variation and whole blood expression of nearby genes.</p><p><strong>Results: </strong>In YFS, the methylation levels of cg06690548 (SLC7A11) were lower in individuals with liver steatosis (Δbeta = - 0.011, FDR = 0.004). Methylation of 9 CpGs associated with GGT and 23 CpGs with FLI in at least two of the discovery cohorts. Methylation at cg06690548 (SLC7A11) and the majority of the CpGs associating with GGT or FLI had the strongest association in the two oldest generations of YFS-3G follow-up (ages 43-59y. and 59-93y.), with minor or non-significant association in the youngest generation (ages 6-36y.). Discovered meQTLs for the CpGs did not modulate the association between the methylation levels and GGT or FLI. The expression of the nearby genes mediated only the association between cg06500161 (ABCG1) and cg20544516 (SREBF1) and FLI.</p><p><strong>Conclusions: </strong>Our findings highlight the association between the methylation levels of cg06690548 (SLC7A11) and liver steatosis, describe the dynamic relationship between whole blood DNA methylation and MASLD, and contribute to a deeper understanding of the pathophysiology of liver diseases.</p>","PeriodicalId":10366,"journal":{"name":"Clinical Epigenetics","volume":" ","pages":"22"},"PeriodicalIF":4.4,"publicationDate":"2026-01-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12866020/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145896415","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":"Tumors with mutations in chromatin regulators are associated with higher mutational burden and improved response to checkpoint immunotherapy.","authors":"Marija Gjorgjievska, Djansel Bukovec, Sanja Mehandziska, Milan Risteski, Ivan Kungulovski, Zan Mitrev, Goran Kungulovski","doi":"10.1186/s13148-025-02038-0","DOIUrl":"10.1186/s13148-025-02038-0","url":null,"abstract":"<p><p>In recent years, it has been demonstrated that many of the pervasive genetic defects throughout cancerogenesis occur in genes encoding chromatin regulators (CRs). We analyzed the distribution and characteristics of well-studied CRs across tens of thousands of tumor samples. Our analysis revealed that tumors with mutations in CRs are associated with high tumor mutational burden (TMB). The co-occurrence of mutations in multiple CRs was linked with a further increase in TMB. Given that TMB may predict the clinical response to immune checkpoint inhibitor (ICI) treatment, we investigated the relationship between mutations in CRs and ICI response. We found that patients harboring mutations in CRs exhibited improved responses to ICI treatment, comparable to those with deficiencies in canonical DNA repair pathways. Overall, this study uncovered significant relationships between mutations in chromatin regulators and critical features of cancer, underscoring the need for further functional and clinical studies.</p>","PeriodicalId":10366,"journal":{"name":"Clinical Epigenetics","volume":" ","pages":"19"},"PeriodicalIF":4.4,"publicationDate":"2025-12-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12866042/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145877821","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}