Title |
Reduced hydroxymethylation characterizes medulloblastoma while TET and IDH genes are differentially expressed within molecular subgroups
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Published in |
Journal of Neuro-Oncology, March 2018
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DOI | 10.1007/s11060-018-2845-1 |
Pubmed ID | |
Authors |
Karina Bezerra Salomão, Gustavo Alencastro Veiga Cruzeiro, Ricardo Bonfim-Silva, Lenisa Geron, Fernando Ramalho, Fabiano Pinto Saggioro, Luciano Neder Serafini, Daniel Antunes Moreno, Rosane Gomes de Paula Queiroz, Simone dos Santos Aguiar, Izilda Cardinalli, José Andres Yunes, Silvia Regina Brandalise, Maria Sol Brassesco, Carlos Alberto Scrideli, Luiz Gonzaga Tone |
Abstract |
Medulloblastoma (MB) is an embryonal tumour that originates from genetic deregulation of cerebellar developmental pathways and is classified into 4 molecular subgroups: SHH, WNT, group 3, and group 4. Hydroxymethylation levels progressively increases during cerebellum development suggesting a possibility of deregulation in MB pathogenesis. The aim of this study was to investigate global hydroxymethylation levels and changes in TET and IDH gene expression in MB samples compared to control cerebellum samples. The methods utilized were qRT-PCR for gene expression, dot-blot and immunohistochemistry for global hydroxymethylation levels and sequencing for the investigation of IDH mutations. Our results show that global hydroxymethylation level was decreased in MB, and low 5hmC level was associated with the presence of metastasis. TET1 expression levels were decreased in the WNT subgroup, while TET3 expression levels were decreased in the SHH subgroup. Reduced TET3 expression levels were associated with the presence of events such as relapse and death. Higher expression of IDH1 was observed in MB group 3 samples, whereas no mutations were detected in exon 4 of IDH1 and IDH2. These findings suggest that reduction of global hydroxymethylation levels, an epigenetic event, may be important for MB development and/or maintenance, representing a possible target in this tumour and indicating a possible interaction of TET and IDH genes with the developmental pathways specifically activated in the MB subgroups. These genes could be specific targets and markers for each subgroup. |
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Student > Bachelor | 3 | 15% |
Researcher | 2 | 10% |
Professor > Associate Professor | 2 | 10% |
Student > Doctoral Student | 1 | 5% |
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Unknown | 3 | 15% |
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Pharmacology, Toxicology and Pharmaceutical Science | 1 | 5% |
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