000306869 001__ 306869 000306869 005__ 20251210120039.0 000306869 0247_ $$2doi$$a10.1093/noajnl/vdaf159 000306869 0247_ $$2pmid$$apmid:40746948 000306869 0247_ $$2pmc$$apmc:PMC12311925 000306869 037__ $$aDKFZ-2025-02846 000306869 041__ $$aEnglish 000306869 082__ $$a610 000306869 1001_ $$00000-0002-2544-5888$$aTaylor, Aaron Michael$$b0 000306869 245__ $$aA feasibility study of enzymatic methylation sequencing of cell-free DNA from cerebrospinal fluid of pediatric central nervous system tumor patients for molecular classification. 000306869 260__ $$aOxford$$bOxford University Press$$c2025 000306869 3367_ $$2DRIVER$$aarticle 000306869 3367_ $$2DataCite$$aOutput Types/Journal article 000306869 3367_ $$0PUB:(DE-HGF)16$$2PUB:(DE-HGF)$$aJournal Article$$bjournal$$mjournal$$s1765291912_2845852 000306869 3367_ $$2BibTeX$$aARTICLE 000306869 3367_ $$2ORCID$$aJOURNAL_ARTICLE 000306869 3367_ $$00$$2EndNote$$aJournal Article 000306869 520__ $$aArray-based DNA methylation profiling is the gold standard for central nervous system (CNS) tumor molecular classification, but requires over 100 ng input DNA from surgical tissue. Cell-free tumor DNA (cfDNA) in cerebrospinal fluid (CSF) offers an alternative for diagnosis and disease monitoring. This study aimed to test the utilization of enzymatic DNA methylation sequencing (EM-seq) methods to overcome input DNA limitations.We used the NEBNext EM-seq v2 kit on various amounts of cfDNA, as low as 0.1 ng, extracted from archival CSF samples of 10 patients with CNS tumors. Tumor classification was performed via MNP-Flex using CpG sites overlapping those on the MethylationEPIC array.EM-seq provided sufficient genomic coverage for 10 and 1 ng input DNA samples to generate global DNA methylation profiles. Samples with 0.1 ng input showed lower coverage due to read duplication. Methylation levels for CpG sites with at least 5× coverage were highly correlated across various input DNA amounts, indicating that lower input cfDNA can still be used for tumor classification. The MNP-Flex classifier, trained on tissue DNA methylation data, successfully predicted CNS tumor types for 7 out of 10 CSF samples using EM-seq methylation data with only 1 ng of input cfDNA, consistent with diagnoses based on tissue MethylationEPIC classification and/or histopathology. Additionally, we detected focal and arm-level copy number alterations previously identified via clinical cytogenetics of tumor tissue.This study demonstrated the feasibility of CNS tumor molecular classification based on CSF using the EM-seq approach, and establishes potential sample quality limitations for future studies. 000306869 536__ $$0G:(DE-HGF)POF4-312$$a312 - Funktionelle und strukturelle Genomforschung (POF4-312)$$cPOF4-312$$fPOF IV$$x0 000306869 588__ $$aDataset connected to CrossRef, PubMed, , Journals: inrepo02.dkfz.de 000306869 650_7 $$2Other$$aCNS tumor classification 000306869 650_7 $$2Other$$aMNP-flex 000306869 650_7 $$2Other$$acell-free DNA 000306869 650_7 $$2Other$$aenzymatic methylation sequencing 000306869 650_7 $$2Other$$amolecular diagnosis 000306869 7001_ $$aLombardi, Jody T$$b1 000306869 7001_ $$0P:(DE-He78)79506056c05e539af84edf040f0a93ad$$aPatel, Areeba Jamilkhan$$b2$$udkfz 000306869 7001_ $$aTamariz, Ariella$$b3 000306869 7001_ $$00000-0003-3180-2084$$aMartin, Jonathan$$b4 000306869 7001_ $$00000-0003-4422-8376$$aBookland, Markus J$$b5 000306869 7001_ $$00000-0003-1177-2201$$aHersh, David S$$b6 000306869 7001_ $$00000-0001-7302-9734$$aCantor, Evan$$b7 000306869 7001_ $$aSong, Xianyuan$$b8 000306869 7001_ $$0P:(DE-He78)a1f4b408b9155beb2a8f7cba4d04fe88$$aSahm, Felix$$b9$$udkfz 000306869 7001_ $$00000-0003-0364-7443$$aNg, Patrick Kwok-Shing$$b10 000306869 7001_ $$aGell, Joanna J$$b11 000306869 7001_ $$00000-0001-9173-8366$$aLau, Ching C$$b12 000306869 773__ $$0PERI:(DE-600)3009682-0$$a10.1093/noajnl/vdaf159$$gVol. 7, no. 1, p. vdaf159$$n1$$pvdaf159$$tNeuro-oncology advances$$v7$$x2632-2498$$y2025 000306869 909CO $$ooai:inrepo02.dkfz.de:306869$$pVDB 000306869 9101_ $$0I:(DE-588b)2036810-0$$6P:(DE-He78)79506056c05e539af84edf040f0a93ad$$aDeutsches Krebsforschungszentrum$$b2$$kDKFZ 000306869 9101_ $$0I:(DE-588b)2036810-0$$6P:(DE-He78)a1f4b408b9155beb2a8f7cba4d04fe88$$aDeutsches Krebsforschungszentrum$$b9$$kDKFZ 000306869 9131_ $$0G:(DE-HGF)POF4-312$$1G:(DE-HGF)POF4-310$$2G:(DE-HGF)POF4-300$$3G:(DE-HGF)POF4$$4G:(DE-HGF)POF$$aDE-HGF$$bGesundheit$$lKrebsforschung$$vFunktionelle und strukturelle Genomforschung$$x0 000306869 9141_ $$y2025 000306869 915__ $$0StatID:(DE-HGF)0100$$2StatID$$aJCR$$bNEURO-ONCOL ADV : 2022$$d2024-12-18 000306869 915__ $$0StatID:(DE-HGF)0200$$2StatID$$aDBCoverage$$bSCOPUS$$d2024-12-18 000306869 915__ $$0StatID:(DE-HGF)0300$$2StatID$$aDBCoverage$$bMedline$$d2024-12-18 000306869 915__ $$0StatID:(DE-HGF)0501$$2StatID$$aDBCoverage$$bDOAJ Seal$$d2024-04-03T10:37:56Z 000306869 915__ $$0StatID:(DE-HGF)0500$$2StatID$$aDBCoverage$$bDOAJ$$d2024-04-03T10:37:56Z 000306869 915__ $$0StatID:(DE-HGF)0030$$2StatID$$aPeer Review$$bDOAJ : Anonymous peer review$$d2024-04-03T10:37:56Z 000306869 915__ $$0StatID:(DE-HGF)0199$$2StatID$$aDBCoverage$$bClarivate Analytics Master Journal List$$d2024-12-18 000306869 915__ $$0StatID:(DE-HGF)0112$$2StatID$$aWoS$$bEmerging Sources Citation Index$$d2024-12-18 000306869 915__ $$0StatID:(DE-HGF)0150$$2StatID$$aDBCoverage$$bWeb of Science Core Collection$$d2024-12-18 000306869 915__ $$0StatID:(DE-HGF)9900$$2StatID$$aIF < 5$$d2024-12-18 000306869 915__ $$0StatID:(DE-HGF)0561$$2StatID$$aArticle Processing Charges$$d2024-12-18 000306869 915__ $$0StatID:(DE-HGF)0700$$2StatID$$aFees$$d2024-12-18 000306869 9201_ $$0I:(DE-He78)B062-20160331$$kB062$$lB062 Pädiatrische Neuroonkologie$$x0 000306869 9201_ $$0I:(DE-He78)B300-20160331$$kB300$$lKKE Neuropathologie$$x1 000306869 980__ $$ajournal 000306869 980__ $$aVDB 000306869 980__ $$aI:(DE-He78)B062-20160331 000306869 980__ $$aI:(DE-He78)B300-20160331 000306869 980__ $$aUNRESTRICTED