De novo methylation of CpG islands is seen in many cancers, but the general rules governing this process are not known. By analyzing DNA from tumors, as well as normal tissues, and by utilizing a range of published data, we have identified a universal set of tumor targets, each with its own "coefficient" of methylation that is largely correlated with its inherent relative ability to recruit polycomb. This pattern is initially formed by a slow process of de novo methylation that occurs during aging and then undergoes expansion early in tumorigenesis, where we hypothesize that it may act as an inhibitor of development-associated gene activation.
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http://dx.doi.org/10.1158/0008-5472.CAN-13-3042 | DOI Listing |
J Exp Clin Cancer Res
January 2025
Department of Cancer Research, Institute of Molecular Medicine, University of Southern Denmark, Odense, Denmark.
Background: Despite promising preclinical studies, the application of DNA methyltransferase inhibitors in treating patients with solid cancers has thus far produced only modest outcomes. The presence of intratumoral heterogeneity in response to DNA methyltransferase inhibitors could significantly influence clinical efficacy, yet our understanding of the single-cell response to these drugs in solid tumors remains very limited.
Methods: In this study, we used cancer/testis antigen genes as a model for methylation-dependent gene expression to examine the activity of DNA methyltransferase inhibitors and their potential synergistic effect with histone deacetylase inhibitors at the single-cancer cell level.
NPJ Parkinsons Dis
January 2025
Cleveland Clinic Genome Center, Lerner Research Institute, Cleveland Clinic, Cleveland, OH, 44195, USA.
Parkinson's disease (PD) is the second most prevalent neurodegenerative disorder. However, current treatments only manage symptoms and lack the ability to slow or prevent disease progression. We utilized a systems genetics approach to identify potential risk genes and repurposable drugs for PD.
View Article and Find Full Text PDFTumori
January 2025
IEO, European Institute of Oncology IRCCS, Division of Cancer Prevention and Genetics, Milan, Italy.
Lynch syndrome is a genetic condition predisposing to cancer, particularly colorectal cancer and endometrial cancer, due to germline mutations in MisMatch Repair genes. More rarely, Lynch syndrome is the result of a constitutional promoter methylation. This review summarizes the current knowledge about the role of this epigenetic mechanism in the Lynch syndrome.
View Article and Find Full Text PDFAm J Hum Genet
January 2025
Genetics Institute, Rambam Health Care Campus, Haifa, Israel; Ruth and Bruce Rappaport Faculty of Medicine, Technion-Israel Institute of Technology, Haifa, Israel. Electronic address:
Pathogenic heterozygous variants in CHD4 cause Sifrim-Hitz-Weiss syndrome, a neurodevelopmental disorder associated with brain anomalies, heart defects, macrocephaly, hypogonadism, and additional features with variable expressivity. Most individuals have non-recurrent missense variants, complicating variant interpretation. A few were reported with truncating variants, and their role in disease is unclear.
View Article and Find Full Text PDFPlant Cell
January 2025
National Key Laboratory of Crop Genetic Improvement, Huazhong Agricultural University, Wuhan 430070, China.
Plant architecture greatly contributes to grain yield, but the epigenetic regulation of plant architecture remains elusive. Here, we identified the maize (Zea mays L.) mutant plant architecture 1 (par1), which shows reduced plant height, shorter and narrower leaves, and larger leaf angles than the wild type.
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