Clinical Epigenetics最新文献

{"title":"Cancer-associated fibroblasts reveal aberrant DNA methylation across different types of cancer.","authors":"Marco Schmidt, Tiago Maié, Thorsten Cramer, Ivan G Costa, Wolfgang Wagner","doi":"10.1186/s13148-024-01783-y","DOIUrl":"https://doi.org/10.1186/s13148-024-01783-y","url":null,"abstract":"<p><strong>Background: </strong>Cancer-associated fibroblasts (CAFs) are essential components of the tumor microenvironment and play a critical role in cancer progression. Numerous studies have identified significant molecular differences between CAFs and normal tissue-associated fibroblasts (NAFs). In this study, we isolated CAFs and NAFs from liver tumors and conducted a comprehensive analysis of their DNA methylation profiles, integrating our finding with data from studies on other cancer types.</p><p><strong>Results: </strong>Our analysis revealed that several CAF samples exhibited aberrant DNA methylation patterns, which corresponded with altered gene expression levels. Notably, DNA methylation at liver CAF-specific CpG sites was linked to survival outcomes in liver cancer datasets. An integrative analysis using publicly available datasets from various cancer types, including lung, prostate, esophageal, and gastric cancers, uncovered common epigenetic abnormalities across these cancers. Among the consistently altered CpGs were cg09809672 (EDARADD), cg07134930 (HDAC4), and cg05935904 (intergenic). These methylation changes were associated with prognosis across multiple cancer types.</p><p><strong>Conclusion: </strong>The activation of CAFs by the tumor microenvironment seems to be associated with distinct epigenetic modifications. Remarkably, similar genomic regions tend to undergo hypomethylation in CAFs across different studies and cancer types. Our findings suggest that CAF-associated DNA methylation changes hold potential as prognostic biomarkers. However, further research and validation are necessary to develop and apply such signatures in a clinical setting.</p>","PeriodicalId":10366,"journal":{"name":"Clinical Epigenetics","volume":"16 1","pages":"164"},"PeriodicalIF":4.8,"publicationDate":"2024-11-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142680999","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":"Associations of epigenetic age acceleration at birth and age 12 years with adolescent cardiometabolic risk: the HOME study.","authors":"Jennifer L Arzu, Karl T Kelsey, George D Papandonatos, Kim M Cecil, Aimin Chen, Scott M Langevin, Bruce P Lanphear, Kimberly Yolton, Jessie P Buckley, Joseph M Braun","doi":"10.1186/s13148-024-01779-8","DOIUrl":"10.1186/s13148-024-01779-8","url":null,"abstract":"<p><strong>Background: </strong>Cardiometabolic risk factors among youth are rising. Epigenetic age acceleration, a biomarker for aging and disease-risk, has been associated with adiposity in children, but its association with other cardiometabolic risk markers remains understudied. We employed data from the Health Outcomes and Measures of the Environment (HOME) study, a prospective pregnancy and birth cohort in the greater Cincinnati metropolitan area, to examine whether accelerated epigenetic age at birth as well as accelerated epigenetic age and faster pace of biological aging at age 12 years were associated with higher cardiometabolic risk in adolescents.</p><p><strong>Results: </strong>After adjusting for potential confounders, including estimated cell type proportions, epigenetic gestational age acceleration at birth, derived from the Bohlin, Knight, and Haftorn clocks using cord blood DNA methylation data, was not associated with cardiometabolic risk z-scores or individual cardiometabolic risk score components (visceral fat, leptin to adiponectin ratio, HOMA-IR, triglycerides to HDL-C ratio, HbA1c, or systolic blood pressure) at age 12 years. We also did not observe any associations of epigenetic age acceleration, calculated with Horvath's skin and blood, Hannum's, and Wu's epigenetic clocks using peripheral blood at age 12 years, with these same cardiometabolic risk markers. In contrast, faster pace of biological aging was associated with higher cardiometabolic risk [βs (95% CIs)] cardiometabolic risk score 0.25 (0.07, 0.42); visceral fat 0.21 (0.05, 0.38); and hemoglobin A1c 0.23 (0.05, 0.41) per standard deviation increase in pace of biological aging. Faster pace of biological aging was also positively associated with systolic blood pressure, triglycerides to HDL-C ratio, HOMA-IR, and leptin to adiponectin ratio, although these associations were not statistically significant.</p><p><strong>Conclusions: </strong>Our findings provide evidence that faster pace of biological aging was associated with higher cardiometabolic risk score, visceral fat, and HbA1c at age 12 years. Further research is needed to determine whether these associations persist from adolescence through adulthood.</p>","PeriodicalId":10366,"journal":{"name":"Clinical Epigenetics","volume":"16 1","pages":"163"},"PeriodicalIF":4.8,"publicationDate":"2024-11-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142675358","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":"Epigenetic modifications involving ncRNAs in digestive system cancers: focus on histone modification.","authors":"Xiaodi Yin, Jingyi Li, Jiahui Zhao, Weihan Zheng, Aohua Zhang, Jun Ma","doi":"10.1186/s13148-024-01773-0","DOIUrl":"10.1186/s13148-024-01773-0","url":null,"abstract":"<p><p>In recent years, epigenetic modifications have been strongly linked to tumor development, with histone modifications representing a key epigenetic mechanism. In addition, non-coding RNAs (ncRNAs) play a critical role in regulating cancer-related pathways. The abnormal interaction between histone modifications and ncRNAs, both pivotal epigenetic regulators, has been widely observed across various cancer types. Here, we systematically explore the molecular mechanisms through which histone modifications and ncRNAs contribute in the pathogenesis of digestive system cancers, and aberrant ncRNA-mediated histone modifications manipulate various biological behaviors of tumor cells including proliferation, migration, angiogenesis, etc. In addition, we provide new insights into diagnostic, prognostic markers, therapeutic targets and chemoradiation resistance for digestive system cancers from the epigenetic perspective.</p>","PeriodicalId":10366,"journal":{"name":"Clinical Epigenetics","volume":"16 1","pages":"162"},"PeriodicalIF":4.8,"publicationDate":"2024-11-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142675364","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":"Pre-diagnosis blood DNA methylation profiling of twin pairs discordant for breast cancer points to the importance of environmental risk factors.","authors":"Hannes Frederik Bode, Liang He, Jacob V B Hjelmborg, Jaakko Kaprio, Miina Ollikainen","doi":"10.1186/s13148-024-01767-y","DOIUrl":"10.1186/s13148-024-01767-y","url":null,"abstract":"<p><strong>Background: </strong>Assessment of breast cancer (BC) risk generally relies on mammography, family history, reproductive history, and genotyping of major mutations. However, assessing the impact of environmental factors, such as lifestyle, health-related behavior, or external exposures, is still challenging. DNA methylation (DNAm), capturing both genetic and environmental effects, presents a promising opportunity. Previous studies have identified associations and predicted the risk of BC using DNAm in blood; however, these studies did not distinguish between genetic and environmental contributions to these DNAm sites. In this study, associations between DNAm and BC are assessed using paired twin models, which control for shared genetic and environmental effects, allowing testing for associations between DNAm and non-shared environmental exposures and behavior.</p><p><strong>Results: </strong>Pre-diagnosis blood samples of 32 monozygotic (MZ) and 76 dizygotic (DZ) female twin pairs discordant for BC were collected at the mean age of 56.0 years, with the mean age at diagnosis 66.8 years and censoring 75.2 years. We identified 212 CpGs (p < 6.4*10^-8) and 15 DMRs associated with BC risk across all pairs using paired Cox proportional hazard models. All but one of the BC risks associated with CpGs were hypomethylated, and 198/212 CpGs had their DNAm associated with BC risk independent of genetic effects. According to previous literature, at least five of the top CpGs were related to estrogen signaling. Following a comprehensive two-sample Mendelian randomization analysis, we found evidence supporting a dual causal impact of DNAm at cg20145695 (gene body of NXN, rs480351) with increased risk for estrogen receptor positive BC and decreased risk for estrogen receptor negative BC.</p><p><strong>Conclusion: </strong>While causal effects of DNAm on BC risk are rare, most of the identified CpGs associated with the risk of BC appear to be independent of genetic effects. This suggests that DNAm could serve as a valuable biomarker for environmental risk factors for BC, and may offer potential benefits as a complementary tool to current risk assessment procedures.</p>","PeriodicalId":10366,"journal":{"name":"Clinical Epigenetics","volume":"16 1","pages":"160"},"PeriodicalIF":4.8,"publicationDate":"2024-11-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11574988/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142667454","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":"MOSES: a methylation-based gene association approach for unveiling environmentally regulated genes linked to a trait or disease.","authors":"Soyeon Kim, Yidi Qin, Hyun Jung Park, Rebecca I Caldino Bohn, Molin Yue, Zhongli Xu, Erick Forno, Wei Chen, Juan C Celedón","doi":"10.1186/s13148-024-01776-x","DOIUrl":"10.1186/s13148-024-01776-x","url":null,"abstract":"<p><strong>Background: </strong>DNA methylation is a critical regulatory mechanism of gene expression, influencing various human diseases and traits. While traditional expression quantitative trait loci (eQTL) studies have helped elucidate the genetic regulation of gene expression, there is a growing need to explore environmental influences on gene expression. Existing methods such as PrediXcan and FUSION focus on genotype-based associations but overlook the impact of environmental factors. To address this gap, we present MOSES (methylation-based gene association), a novel approach that utilizes DNA methylation to identify environmentally regulated genes associated with traits or diseases without relying on measured gene expression.</p><p><strong>Results: </strong>MOSES involves training, imputation, and association testing. It employs elastic-net penalized regression models to estimate the influence of CpGs and SNPs (if available) on gene expression. We developed and compared four MOSES versions incorporating different methylation and genetic data: (1) cis-DNA methylation within 1 Mb of promoter regions, (2) both cis-SNPs and cis-CpGs, 3) both cis- and a part of trans- CpGs (±5Mb away) from promoter regions), and 4) long-range DNA methylation (±10 Mb away) from promoter regions. Our analysis using nasal epithelium and white blood cell data from the Epigenetic Variation and Childhood Asthma in Puerto Ricans (EVA-PR) study demonstrated that MOSES, particularly the version incorporating long-range CpGs (MOSES-DNAm 10 M), significantly outperformed existing methods like PrediXcan, MethylXcan, and Biomethyl in predicting gene expression. MOSES-DNAm 10 M identified more differentially expressed genes (DEGs) associated with atopic asthma, particularly those involved in immune pathways, highlighting its superior performance in uncovering environmentally regulated genes. Further application of MOSES to lung tissue data from idiopathic pulmonary fibrosis (IPF) patients confirmed its robustness and versatility across different diseases and tissues.</p><p><strong>Conclusion: </strong>MOSES represents an innovative advancement in gene association studies, leveraging DNA methylation to capture the influence of environmental factors on gene expression. By incorporating long-range CpGs, MOSES-DNAm 10 M provides superior predictive accuracy and gene association capabilities compared to traditional genotype-based methods. This novel approach offers valuable insights into the complex interplay between genetics and the environment, enhancing our understanding of disease mechanisms and potentially guiding therapeutic strategies. The user-friendly MOSES R package is publicly available to advance studies in various diseases, including immune-related conditions like asthma.</p>","PeriodicalId":10366,"journal":{"name":"Clinical Epigenetics","volume":"16 1","pages":"161"},"PeriodicalIF":4.8,"publicationDate":"2024-11-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11574994/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142667453","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":"Comparison of cell type and disease subset chromatin modifications in SLE.","authors":"Katherine Beigel, Xiao-Min Wang, Li Song, Kelly Maurer, Christopher Breen, Deanne Taylor, Daniel Goldman, Michelle Petri, Kathleen E Sullivan","doi":"10.1186/s13148-024-01754-3","DOIUrl":"10.1186/s13148-024-01754-3","url":null,"abstract":"<p><strong>Background: </strong>Systemic lupus erythematosus (SLE) is an autoimmune disease with protean manifestations. There is little understanding of why some organs are specifically impacted in patients and the mechanisms of disease persistence remain unclear. While much work has been done characterizing the DNA methylation status in SLE, there is less information on histone modifications, a more dynamic epigenetic feature. This study identifies two histone marks of activation and the binding of p300 genome-wide in three cell types and three clinical subsets to better understand cell-specific effects and differences across clinical subsets.</p><p><strong>Results: </strong>We examined 20 patients with SLE and 8 controls and found that individual chromatin marks varied considerably across T cells, B cells, and monocytes. When pathways were examined, there was far more concordance with conservation of TNF, IL-2/STAT5, and KRAS pathways across multiple cell types and ChIP data sets. Patients with cutaneous lupus and lupus nephritis generally had less dramatically altered chromatin than the general SLE group. Signals also demonstrated significant overlap with GWAS signals in a manner that did not implicate one cell type more than the others.</p><p><strong>Conclusions: </strong>The pathways identified by altered histone modifications and p300 binding are pathways known to be important from RNA expression studies and recognized pathogenic mechanisms of disease. NFκB and classical inflammatory pathways were strongly associated with increased peak heights across all cell types but were the highest-ranking pathway for all three antibodies in monocytes according to fgsea analysis. IL-6 Jak/STAT3 signaling was the most significant pathway association in T cells marked by H3K27ac change. Therefore, each cell type experiences the disease process distinctly although in all cases there was a strong theme of classical inflammatory pathways. Importantly, this NFκB pathway, so strongly implicated in the patients with generalized SLE, was much less impacted in monocytes when cutaneous lupus was compared to the general SLE cohort and also less impacted in lupus nephritis compared to general SLE. These studies define important cell type differences and emphasize the breadth of the inflammatory effects in SLE.</p>","PeriodicalId":10366,"journal":{"name":"Clinical Epigenetics","volume":"16 1","pages":"159"},"PeriodicalIF":4.8,"publicationDate":"2024-11-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11566291/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142616085","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":"Correction: Epigenetic patterns, accelerated biological aging, and enhanced epigenetic drift detected 6 months following COVID‑19 infection: insights from a genome‑wide DNA methylation study.","authors":"Luciano Calzari, Davide Fernando Dragani, Lucia Zanotti, Elvira Inglese, Romano Danesi, Rebecca Cavagnola, Alberto Brusati, Francesco Ranucci, Anna Maria Di Blasio, Luca Persani, Irene Campi, Sara De Martino, Antonella Farsetti, Veronica Barbi, Michela Gottardi Zamperla, Giulia Nicole Baldrighi, Carlo Gaetano, Gianfranco Parati, Davide Gentilini","doi":"10.1186/s13148-024-01764-1","DOIUrl":"10.1186/s13148-024-01764-1","url":null,"abstract":"","PeriodicalId":10366,"journal":{"name":"Clinical Epigenetics","volume":"16 1","pages":"158"},"PeriodicalIF":4.8,"publicationDate":"2024-11-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11566271/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142616087","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 biomarkers and myopia: a multi-omics study integrating GWAS, mQTL and eQTL data.","authors":"Xing-Xuan Dong, Dong-Ling Chen, Hui-Min Chen, Dan-Lin Li, Dan-Ning Hu, Carla Lanca, Andrzej Grzybowski, Chen-Wei Pan","doi":"10.1186/s13148-024-01772-1","DOIUrl":"10.1186/s13148-024-01772-1","url":null,"abstract":"<p><strong>Background: </strong>This study aimed to identify DNA methylation biomarkers associated with myopia using summary-data-based Mendelian randomization (SMR).</p><p><strong>Methods: </strong>A systematic search of the PubMed, Web of Science, Cochrane Library, and Embase databases was conducted up to March 27, 2024. SMR analyses were performed to integrate genome-wide association study (GWAS) with methylation quantitative trait loci (mQTL) and expression quantitative trait loci (eQTL) studies. The heterogeneity in the dependent instrument (HEIDI) test was utilized to distinguish pleiotropic associations from linkage disequilibrium.</p><p><strong>Results: </strong>The systematic review identified 26 DNA methylation biomarkers in five studies, with no overlap observed among those identified by different studies. After integrating GWAS with multi-omics data of mQTL and eQTL, six genes were significantly associated with myopia: PRMT6 (cg00944433 and cg15468180), SH3YL1 (cg03299269, cg11361895, and cg13354988), ZKSCAN4 (cg01192291), GATS (cg17830204), NPAT (cg04826772), and UBE2I (cg03545757 and cg08025960).</p><p><strong>Conclusions: </strong>We identified six methylation biomarkers associated with the risk of myopia that may be helpful to elucidate the etiology mechanisms of myopia. Further experimental validation studies are required to corroborate these findings.</p>","PeriodicalId":10366,"journal":{"name":"Clinical Epigenetics","volume":"16 1","pages":"157"},"PeriodicalIF":4.8,"publicationDate":"2024-11-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11562087/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142616089","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 classifier to diagnose pancreatic ductal adenocarcinoma metastases from different anatomical sites.","authors":"Teodor G Calina, Eilís Perez, Elena Grafenhorst, Jamal Benhamida, Simon Schallenberg, Adrian Popescu, Ines Koch, Tobias Janik, BaoQing Chen, Jana Ihlow, Stephanie Roessler, Benjamin Goeppert, Bruno Sinn, Marcus Bahra, George A Calin, Eliane T Taube, Uwe Pelzer, Christopher C M Neumann, David Horst, Erik Knutsen, David Capper, Mihnea P Dragomir","doi":"10.1186/s13148-024-01768-x","DOIUrl":"10.1186/s13148-024-01768-x","url":null,"abstract":"<p><strong>Background: </strong>We have recently constructed a DNA methylation classifier that can discriminate between pancreatic ductal adenocarcinoma (PAAD) liver metastasis and intrahepatic cholangiocarcinoma (iCCA) with high accuracy (PAAD-iCCA-Classifier). PAAD is one of the leading causes of cancer of unknown primary and diagnosis is based on exclusion of other malignancies. Therefore, our focus was to investigate whether the PAAD-iCCA-Classifier can be used to diagnose PAAD metastases from other sites.</p><p><strong>Methods: </strong>For this scope, the anomaly detection filter of the initial classifier was expanded by 8 additional mimicker carcinomas, amounting to a total of 10 carcinomas in the negative class. We validated the updated version of the classifier on a validation set, which consisted of a biological cohort (n = 3579) and a technical one (n = 15). We then assessed the performance of the classifier on a test set, which included a positive control cohort of 16 PAAD metastases from various sites and a cohort of 124 negative control samples consisting of 96 breast cancer metastases from 18 anatomical sites and 28 carcinoma metastases to the brain.</p><p><strong>Results: </strong>The updated PAAD-iCCA-Classifier achieved 98.21% accuracy on the biological validation samples, and on the technical validation ones it reached 100%. The classifier also correctly identified 15/16 (93.75%) metastases of the positive control as PAAD, and on the negative control, it correctly classified 122/124 samples (98.39%) for a 97.85% overall accuracy on the test set. We used this DNA methylation dataset to explore the organotropism of PAAD metastases and observed that PAAD liver metastases are distinct from PAAD peritoneal carcinomatosis and primary PAAD, and are characterized by specific copy number alterations and hypomethylation of enhancers involved in epithelial-mesenchymal-transition.</p><p><strong>Conclusions: </strong>The updated PAAD-iCCA-Classifier (available at https://classifier.tgc-research.de/ ) can accurately classify PAAD samples from various metastatic sites and it can serve as a diagnostic aid.</p>","PeriodicalId":10366,"journal":{"name":"Clinical Epigenetics","volume":"16 1","pages":"156"},"PeriodicalIF":4.8,"publicationDate":"2024-11-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11550539/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142616092","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":"TET2 mutation in acute myeloid leukemia: biology, clinical significance, and therapeutic insights.","authors":"Qiang Gao, Kefeng Shen, Min Xiao","doi":"10.1186/s13148-024-01771-2","DOIUrl":"10.1186/s13148-024-01771-2","url":null,"abstract":"<p><p>TET2 is a critical gene that regulates DNA methylation, encoding a dioxygenase protein that plays a vital role in the regulation of genomic methylation and other epigenetic modifications, as well as in hematopoiesis. Mutations in TET2 are present in 7%-28% of adult acute myeloid leukemia (AML) patients. Despite this, the precise mechanisms by which TET2 mutations contribute to malignant transformation and how these insights can be leveraged to enhance treatment strategies for AML patients with TET2 mutations remain unclear. In this review, we provide an overview of the functions of TET2, the effects of its mutations, its role in clonal hematopoiesis, and the possible mechanisms of leukemogenesis. Additionally, we explore the mutational landscape across different AML subtypes and present recent promising preclinical research findings.</p>","PeriodicalId":10366,"journal":{"name":"Clinical Epigenetics","volume":"16 1","pages":"155"},"PeriodicalIF":4.8,"publicationDate":"2024-11-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11550532/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142616093","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}