Study of TET gene expression and hydroxymethylation levels in medulloblastoma

• Grant number: 13/15125-3
• Support type: Scholarships in Brazil - Doctorate
• Effective date (Start): March 01, 2014
• Effective date (End): June 11, 2017
• Field of knowledge: Health Sciences - Medicine
• Principal Investigator: Luiz Gonzaga Tone
• Grantee: Karina Bezerra Salomão Xavier
• Home Institution: Faculdade de Medicina de Ribeirão Preto (FMRP). Universidade de São Paulo (USP). Ribeirão Preto , SP, Brazil
• Associated scholarship(s): 15/15231-3 - Epigenetic regulation of retroelements by TET enzymes in neural precursor cells, BE.EP.DR

Abstract

Medulloblastoma (MB) originates in the cerebellum and represents the most common malignant brain tumor in childhood. The MB is traditionally divided into five histologic groups related to prognosis: MB desmoplastic, nodular, classic, anaplastic or anaplastic large cell. In recent years, gene expression studies of MB allowed the classification of the tumor into four subgroups: (1) WNT, (2) SHH, (3) overexpression of MYC and (4) genetic abnormalities nonspecific. The epigenetic changes such as hypermethylation of tumor suppressor genes play an important role in the development of MB. The reduction of hydroxymethylation compared to normal tissue associated with a decrease in TET gene expression was demonstrated in several tumors, function deregulation of the TET enzymes may also be associated with mutations in IDH1 and IDH2 genes; but nothing is known about this mechanism or TET expression in MB. This study aims to determine the expression of genes TET1, TET2, TET3, IDH1 and IDH2 (normal and mutant); global hydroxymethylation levels and methylation or hydroxymethylation in genes of SHH, WNT, NOTCH and BMP pathways in MB patients samples. To evaluate expression will be used real-time PCR with TaqMan. Sequencing of samples will be conducted to evaluate mutations in IDH1 and IDH2. Hydroxymethylation levels will be evaluated with dot-blot hybridization method. Methylation and hydroxymethylation in genes of pathways will be evaluated by real-time PCR associated with 5-mC and 5-hmC immunoprecipitation.

Scientific publications

(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)

SALOMAO, KARINA BEZERRA; VEIGA CRUZEIRO, GUSTAVO ALENCASTRO; BONFIM-SILVA, RICARDO; GERON, LENISA; RAMALHO, FERNANDO; SAGGIORO, FABIANO PINTO; SERAFINI, LUCIANO NEDER; ANTUNES MORENO, DANIEL; DE PAULA QUEIROZ, ROSANE GOMES; AGUIAR, SIMONE DOS SANTOS; CARDINALLI, IZILDA; YUNES, JOSE ANDRES; BRANDALISE, SILVIA REGINA; BRASSESCO, MARIA SOL; SCRIDELI, CARLOS ALBERTO; TONE, LUIZ GONZAGA. Reduced hydroxymethylation characterizes medulloblastoma while TET and IDH genes are differentially expressed within molecular subgroups. JOURNAL OF NEURO-ONCOLOGY, v. 139, n. 1, p. 33-42, AUG 2018. Web of Science Citations: 0.

Academic Publications

(References retrieved automatically from State of São Paulo Research Institutions)

XAVIER, Karina Bezerra Salomão. Study of TETs genes expression and hydroxymethylation levels in medulloblastoma. 2017. Doctoral Thesis - Universidade de São Paulo (USP). Faculdade de Medicina de Ribeirão Preto Ribeirão Preto.