RT Journal Article T1 Loss of 5hmC identifies a new type of aberrant DNA hypermethylation in glioma. A1 Fernandez, Agustin F A1 Bayon, Gustavo F A1 Sierra, Marta I A1 Urdinguio, Rocio G A1 Toraño, Estela G A1 Garcia, Maria G A1 Carella, Antonella A1 Lopez, Virginia A1 Santamarina, Pablo A1 Perez, Raul F A1 Belmonte, Thalia A1 Tejedor, Juan Ramon A1 Cobo, Isabel A1 Menendez, Pablo A1 Mangas, Cristina A1 Ferrero, Cecilia A1 Rodrigo, Luis A1 Astudillo, Aurora A1 Ortea, Ignacio A1 Cueto Diaz, Sergio A1 Rodriguez-Gonzalez, Pablo A1 Garcia Alonso, J Ignacio A1 Mollejo, Manuela A1 Melendez, Barbara A1 Dominguez, Gemma A1 Bonilla, Felix A1 Fraga, Mario F K1 5-Methylcytosine K1 Biomarkers, tumor K1 Case-control studies K1 CpG islands K1 DNA methylation AB Aberrant DNA hypermethylation is a hallmark of cancer although the underlying molecular mechanisms are still poorly understood. To study the possible role of 5-hydroxymethylcytosine (5hmC) in this process we analyzed the global and locus-specific genome-wide levels of 5hmC and 5-methylcytosine (5mC) in human primary samples from 12 non-tumoral brains and 53 gliomas. We found that the levels of 5hmC identified in non-tumoral samples were significantly reduced in gliomas. Strikingly, hypo-hydroxymethylation at 4627 (9.3%) CpG sites was associated with aberrant DNA hypermethylation and was strongly enriched in CpG island shores. The DNA regions containing these CpG sites were enriched in H3K4me2 and presented a different genuine chromatin signature to that characteristic of the genes classically aberrantly hypermethylated in cancer. As this 5mC gain is inversely correlated with loss of 5hmC and has not been identified with classical sodium bisulfite-based technologies, we conclude that our data identifies a novel 5hmC-dependent type of aberrant DNA hypermethylation in glioma. PB Oxford University Press YR 2018 FD 2018-05-29 LK http://hdl.handle.net/10668/12561 UL http://hdl.handle.net/10668/12561 LA en NO Fernandez AF, Bayón GF, Sierra MI, Urdinguio RG, Toraño EG, García MG, et al. C Loss of 5hmC identifies a new type of aberrant DNA hypermethylation in glioma. Hum Mol Genet. 2018 Sep 1;27(17):3046-3059 DS RISalud RD Apr 5, 2025