Single-nucleus chromatin accessibility reveals intratumoral epigenetic heterogeneity in IDH1 mutant gliomas
DC Field | Value | Language |
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dc.contributor.author | Al-Ali, Ruslan | - |
dc.contributor.author | Bauer, Katharina | - |
dc.contributor.author | Park, Jong-Whi | - |
dc.contributor.author | Al Abdulla, Ruba | - |
dc.contributor.author | Fermi, Valentina | - |
dc.contributor.author | von Deimling, Andreas | - |
dc.contributor.author | Herold-Mende, Christel | - |
dc.contributor.author | Mallm, Jan-Philipp | - |
dc.contributor.author | Herrmann, Carl | - |
dc.contributor.author | Wick, Wolfgang | - |
dc.contributor.author | Turcan, Sevin | - |
dc.date.accessioned | 2022-02-28T07:40:25Z | - |
dc.date.available | 2022-02-28T07:40:25Z | - |
dc.date.created | 2022-02-28 | - |
dc.date.issued | 2019-12 | - |
dc.identifier.issn | 2051-5960 | - |
dc.identifier.uri | https://scholarworks.bwise.kr/gachon/handle/2020.sw.gachon/83590 | - |
dc.description.abstract | The presence of genome-wide DNA hypermethylation is a hallmark of lower grade gliomas (LGG) with isocitrate dehydrogenase (IDH) mutations. Further molecular classification of IDH mutant gliomas is defined by the presence (IDHmut-codel) or absence (IDHmut-noncodel) of hemizygous codeletion of chromosome arms 1p and 19q. Despite the DNA hypermethylation seen in bulk tumors, intra-tumoral heterogeneity at the epigenetic level has not been thoroughly analyzed. To address this question, we performed the first epigenetic profiling of single cells in a cohort of 5 gliomas with IDH1 mutation using single nucleus Assay for Transposase-Accessible Chromatin with high-throughput sequencing (snATAC-seq). Using the Fluidigm HT IFC microfluidics platform, we generated chromatin accessibility maps from 336 individual nuclei, and identified variable promoter accessibility of non-coding RNAs in LGGs. Interestingly, local chromatin structures of several non-coding RNAs are significant factors that contribute to heterogeneity, and show increased promoter accessibility in IDHmut-noncodel samples. As an example for clinical significance of this result, we identify CYTOR as a poor prognosis factor in gliomas with IDH mutation. Open chromatin assay points to differential accessibility of non-coding RNAs as an important source of epigenetic heterogeneity within individual tumors and between molecular subgroups. Rare populations of nuclei that resemble either IDH mutant molecular group co-exist within IDHmut-noncodel and IDHmut-codel groups, and along with non-coding RNAs may be an important issue to consider for future studies, as they may help guide predict treatment response and relapse. | - |
dc.language | 영어 | - |
dc.language.iso | en | - |
dc.publisher | BMC | - |
dc.relation.isPartOf | ACTA NEUROPATHOLOGICA COMMUNICATIONS | - |
dc.title | Single-nucleus chromatin accessibility reveals intratumoral epigenetic heterogeneity in IDH1 mutant gliomas | - |
dc.type | Article | - |
dc.type.rims | ART | - |
dc.description.journalClass | 1 | - |
dc.identifier.wosid | 000509587000004 | - |
dc.identifier.doi | 10.1186/s40478-019-0851-y | - |
dc.identifier.bibliographicCitation | ACTA NEUROPATHOLOGICA COMMUNICATIONS, v.7, no.1 | - |
dc.description.isOpenAccess | N | - |
dc.identifier.scopusid | 2-s2.0-85076284085 | - |
dc.citation.title | ACTA NEUROPATHOLOGICA COMMUNICATIONS | - |
dc.citation.volume | 7 | - |
dc.citation.number | 1 | - |
dc.contributor.affiliatedAuthor | Park, Jong-Whi | - |
dc.type.docType | Article | - |
dc.subject.keywordPlus | READ ALIGNMENT | - |
dc.subject.keywordPlus | CELL | - |
dc.subject.keywordPlus | MUTATIONS | - |
dc.subject.keywordPlus | MACROPHAGE | - |
dc.subject.keywordPlus | REGULATOR | - |
dc.subject.keywordPlus | PHENOTYPE | - |
dc.subject.keywordPlus | MIGRATION | - |
dc.subject.keywordPlus | OLIG2 | - |
dc.relation.journalResearchArea | Neurosciences & Neurology | - |
dc.relation.journalWebOfScienceCategory | Neurosciences | - |
dc.description.journalRegisteredClass | scie | - |
dc.description.journalRegisteredClass | scopus | - |
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