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

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Salomao, Karina Bezerra ^{[1, 2, 3]} ; Veiga Cruzeiro, Gustavo Alencastro ^{[1, 2, 3]} ; Bonfim-Silva, Ricardo ^{[2, 3]} ; Geron, Lenisa ^{[1, 2, 3]} ; Ramalho, Fernando ^{[3, 4]} ; Saggioro, Fabiano Pinto ^{[3, 4]} ; Serafini, Luciano Neder ^{[3, 4]} ; Antunes Moreno, Daniel ^{[2, 3]} ; de Paula Queiroz, Rosane Gomes ^{[1, 2, 3]} ; Aguiar, Simone dos Santos ^[5] ; Cardinalli, Izilda ^[5] ; Yunes, Jose Andres ^[5] ; Brandalise, Silvia Regina ^[5] ; Brassesco, Maria Sol ^{[3, 6]} ; Scrideli, Carlos Alberto ^{[1, 2, 3]} ; Tone, Luiz Gonzaga ^{[1, 2, 3]}

Afiliação do(s) autor(es)

^[1] Univ Sao Paulo, Dept Paediat, 3900 Bandeirantes Ave, BR-14049900 Ribeirao Preto, SP - Brazil

^[2] Univ Sao Paulo, Dept Genet, 3900 Bandeirantes Ave, BR-14049900 Ribeirao Preto, SP - Brazil

^[3] Univ Sao Paulo, Ribeirao Preto Sch Med, 3900 Bandeirantes Ave, BR-14049900 Ribeirao Preto, SP - Brazil

^[4] Univ Sao Paulo, Dept Pathol, 3900 Bandeirantes Ave, BR-14049900 Ribeirao Preto, SP - Brazil

^[5] Univ Campinas UNICAMP, Boldrini Ctr Children, Campinas, SP - Brazil

^[6] Univ Sao Paulo, Fac Philosophy Sci & Letters Ribeirao Preto, 3900 Bandeirantes Ave, BR-14049900 Ribeirao Preto, SP - Brazil

• Tipo de documento: Artigo Científico
• Fonte: JOURNAL OF NEURO-ONCOLOGY; v. 139, n. 1, p. 33-42, AUG 2018.
• Citações Web of Science: 0

Resumo

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. (AU)

• Processo FAPESP: 13/15125-3 - Estudo da expressão dos genes TET e níveis de hidroximetilação em meduloblastoma.
• Beneficiário: Karina Bezerra Salomão Xavier
• Modalidade de apoio: Bolsas no Brasil - Doutorado
• Processo FAPESP: 14/20341-0 - Interação entre alvos terapêuticos emergentes e vias de desenvolvimento associadas à tumorigênese: ênfase em neoplasias da criança e do adolescente
• Beneficiário: Luiz Gonzaga Tone
• Modalidade de apoio: Auxílio à Pesquisa - Temático