{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,15]],"date-time":"2026-07-15T14:46:52Z","timestamp":1784126812953,"version":"3.55.0"},"reference-count":49,"publisher":"Oxford University Press (OUP)","issue":"1","license":[{"start":{"date-parts":[[2020,1,8]],"date-time":"2020-01-08T00:00:00Z","timestamp":1578441600000},"content-version":"vor","delay-in-days":7,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"DOI":"10.13039\/100008533","name":"Case Comprehensive Cancer Center","doi-asserted-by":"publisher","award":["NCI P30CA0437093"],"award-info":[{"award-number":["NCI P30CA0437093"]}],"id":[{"id":"10.13039\/100008533","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Computational Genomic Epidemiology of Cancer","award":["NCI 5T32CA094186-17"],"award-info":[{"award-number":["NCI 5T32CA094186-17"]}]},{"name":"Computational Genomic Epidemiology of Cancer","award":["NCI R01 CA174737"],"award-info":[{"award-number":["NCI R01 CA174737"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2020,1,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:sec>\n                  <jats:title>Background<\/jats:title>\n                  <jats:p>Gliomas are the most common type of primary brain tumor and one of many cancers where males are diagnosed with greater frequency than females. However, little is known about the sex-based molecular differences in glioblastomas (GBMs) or lower grade glioma (non-GBM) subtypes. DNA methylation is an epigenetic mechanism involved in regulating gene transcription. In glioma and other cancers, hypermethylation of specific gene promoters downregulates transcription and may have a profound effect on patient outcome. The purpose of this study was to determine if sex-based methylation differences exist in different glioma subtypes.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Methods<\/jats:title>\n                  <jats:p>Molecular and clinical data from glioma patients were obtained from The Cancer Genome Atlas and grouped according to tumor grade and molecular subtype (IDH1\/2 mutation and 1p\/19q chromosomal deletion). Sex-specific differentially methylated probes (DMPs) were identified in each subtype and further analyzed to determine if they were part of differentially methylated regions (DMRs) or associated with differentially methylated DNA transcription regulatory binding motifs.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Results<\/jats:title>\n                  <jats:p>Analysis of methylation data in 4 glioma subtypes revealed unique sets of both sex-specific DMPs and DMRs in each subtype. Motif analysis based on DMP position also identified distinct sex-based sets of DNA-binding motifs that varied according to glioma subtype. Downstream targets of 2 of the GBM-specific transcription binding sites, NFAT5 and KLF6, showed differential gene expression consistent with increased methylation mediating downregulation.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Conclusion<\/jats:title>\n                  <jats:p>DNA methylation differences between males and females in 4 glioma molecular subtypes suggest an important, sex-specific role for DNA methylation in epigenetic regulation of gliomagenesis.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1093\/noajnl\/vdaa002","type":"journal-article","created":{"date-parts":[[2020,1,8]],"date-time":"2020-01-08T08:09:54Z","timestamp":1578470994000},"source":"Crossref","is-referenced-by-count":17,"title":["Gliomas display distinct sex-based differential methylation patterns based on molecular subtype"],"prefix":"10.1093","volume":"2","author":[{"given":"Mette L","family":"Johansen","sequence":"first","affiliation":[{"name":"Department of Molecular Biology and Microbiology, Case Western Reserve University School of Medicine, Cleveland, Ohio, USA"},{"name":"Case Comprehensive Cancer Center, Case Western Reserve University School of Medicine, Cleveland, Ohio, USA"},{"name":"Department of Population and Quantitative Health Sciences, Case Western Reserve University School of Medicine, Cleveland, Ohio, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"L C","family":"Stetson","sequence":"first","affiliation":[{"name":"Department of Pathology, Case Western Reserve University School of Medicine, Cleveland, Ohio, USA"},{"name":"Case Comprehensive Cancer Center, Case Western Reserve University School of Medicine, Cleveland, Ohio, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vachan","family":"Vadmal","sequence":"first","affiliation":[{"name":"Case Comprehensive Cancer Center, Case Western Reserve University 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