DNA methylation loss promotes immune evasion of tumours with high mutation and copy number load

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dc.contributor.authorJung, Hyunchulko
dc.contributor.authorKim, Hong Sookko
dc.contributor.authorKim, Jeong Yeonko
dc.contributor.authorSun, Jong-Muko
dc.contributor.authorAhn, Jin Seokko
dc.contributor.authorAhn, Myung-Juko
dc.contributor.authorPark, Keunchilko
dc.contributor.authorEsteller, Manelko
dc.contributor.authorLee, Se-Hoonko
dc.contributor.authorChoi, Jung Kyoonko
dc.date.accessioned2019-10-08T09:20:04Z-
dc.date.available2019-10-08T09:20:04Z-
dc.date.created2019-10-07-
dc.date.created2019-10-07-
dc.date.issuedACCEPT-
dc.identifier.citationNATURE COMMUNICATIONS, v.10-
dc.identifier.issn2041-1723-
dc.identifier.urihttp://hdl.handle.net/10203/267847-
dc.description.abstractMitotic cell division increases tumour mutation burden and copy number load, predictive markers of the clinical benefit of immunotherapy. Cell division correlates also with genomic demethylation involving methylation loss in late-replicating partial methylation domains. Here we find that immunomodulatory pathway genes are concentrated in these domains and transcriptionally repressed in demethylated tumours with CpG island promoter hyper-methylation. Global methylation loss correlated with immune evasion signatures independently of mutation burden and aneuploidy. Methylome data of our cohort (n = 60) and a published cohort (n = 81) in lung cancer and a melanoma cohort (n = 40) consistently demonstrated that genomic methylation alterations counteract the contribution of high mutation burden and increase immunotherapeutic resistance. Higher predictive power was observed for methylation loss than mutation burden. We also found that genomic hypo-methylation correlates with the immune escape signatures of aneuploid tumours. Hence, DNA methylation alterations implicate epigenetic modulation in precision immunotherapy.-
dc.languageEnglish-
dc.publisherNATURE PUBLISHING GROUP-
dc.titleDNA methylation loss promotes immune evasion of tumours with high mutation and copy number load-
dc.typeArticle-
dc.identifier.wosid000486566400018-
dc.identifier.scopusid2-s2.0-85072399976-
dc.type.rimsART-
dc.citation.volume10-
dc.citation.publicationnameNATURE COMMUNICATIONS-
dc.identifier.doi10.1038/s41467-019-12159-9-
dc.contributor.localauthorChoi, Jung Kyoon-
dc.contributor.nonIdAuthorKim, Hong Sook-
dc.contributor.nonIdAuthorKim, Jeong Yeon-
dc.contributor.nonIdAuthorSun, Jong-Mu-
dc.contributor.nonIdAuthorAhn, Jin Seok-
dc.contributor.nonIdAuthorAhn, Myung-Ju-
dc.contributor.nonIdAuthorPark, Keunchil-
dc.contributor.nonIdAuthorEsteller, Manel-
dc.contributor.nonIdAuthorLee, Se-Hoon-
dc.description.isOpenAccessN-
dc.type.journalArticleArticle-
dc.subject.keywordPlusCHROMOSOMAL INSTABILITY-
dc.subject.keywordPlusPD-1 BLOCKADE-
dc.subject.keywordPlusENCODE DATA-
dc.subject.keywordPlusCANCER-
dc.subject.keywordPlusHYPOMETHYLATION-
dc.subject.keywordPlusDEMETHYLATION-
dc.subject.keywordPlusDATABASE-
dc.subject.keywordPlusCELLS-
dc.subject.keywordPlusIMMUNOTHERAPY-
dc.subject.keywordPlusNEOANTIGENS-
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BiS-Journal Papers(저널논문)
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