Details

Autor(en) / Beteiligte

• Bezerra Salomão, Karina
• Cruzeiro, Gustavo Alencastro Veiga
• Bonfim-Silva, Ricardo
• Geron, Lenisa
• Ramalho, Fernando
• Pinto Saggioro, Fabiano
• Serafini, Luciano Neder
• Antunes Moreno, Daniel
• de Paula Queiroz, Rosane Gomes
• dos Santos Aguiar, Simone
• Cardinalli, Izilda
• Yunes, José Andres
• Brandalise, Silvia Regina
• Brassesco, Maria Sol
• Scrideli, Carlos Alberto
• Gonzaga Tone, Luiz

Titel

Reduced hydroxymethylation characterizes medulloblastoma while TET and IDH genes are differentially expressed within molecular subgroups

Ist Teil von

• Journal of neuro-oncology, 2018-08, Vol.139 (1), p.33-42

Ort / Verlag

New York: Springer US

Erscheinungsjahr

2018

Quelle

MEDLINE

Beschreibungen/Notizen

• Introduction 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. Methods 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. Results 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 . Conclusion 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.