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Mutational profile of glioblastoma primary cultures

Grant number: 12/19590-0
Support Opportunities:Regular Research Grants
Duration: April 01, 2013 - September 30, 2015
Field of knowledge:Biological Sciences - Genetics - Human and Medical Genetics
Principal Investigator:Rui Manuel Vieira Reis
Grantee:Rui Manuel Vieira Reis
Host Institution: Hospital do Câncer de Barretos. Fundação Pio XII (FP). Barretos , SP, Brazil
Associated researchers: Carlos Clara ; Gisele Caravina ; Guilherme Corrêa de Oliveira ; Jeremy Andrew Squire

Abstract

Gliobastomas are the most frequent and malignant brain neoplasia among the central nervous system tumors. These are incurable neoplasias, with mean survival of 13 months, and less than 2% of the patients reach 5 years post treatment. The low success in the treatment of these tumors are, in part, due to the little understanding of their molecular bases. Moreover, several in vitro studies are performed in immortalized cells, which frequently are not accurate in the representation of the primary tumors, since they had molecular alterations during the immortalization process. Therefore, the objective of this project is the molecular characterization of point mutations present in oncogenesis-related genes (through next generation sequencing - Ion Torrent) in the primary cells of glioblastoma obtained on Barretos Cancer Hospital. This data will be integrated with the chromosomal profile of tumors. These results will be further compared to the alterations found in primary tumors from the same patients. Consequently, we aim to select the primary cultures that harbour the same molecular profile of the primary tumors, which will be further used as in vitro models for assessing the biological function of genes associated with gliomas and to perform the screening of novel drugs in order to identify more effective and specific agents for glioblastomas. Additionally, the establishment of a mutation panel specific of glioblastoma will be of major importance for a future implementation in a routine of brain tumors diagnosis. (AU)

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Scientific publications (13)
(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)
PINTO, FILIPE; COSTA, ANGELA M.; ANDRADE, RAQUEL P.; REIS, RUI MANUEL. Brachyury Is Associated with Glioma Differentiation and Response to Temozolomide. NEUROTHERAPEUTICS, v. 17, n. 4, p. 13-pg., . (12/19590-0)
BRUNHARA, BRUNO B.; BECKER, ALINE P.; NEDER, LUCIANO; GONCALVES, PAOLA G.; DE OLIVEIRA, CRISTIANE; CLARA, CARLOS A.; REIS, RUI M.; BIDINOTTO, LUCAS T.. Evaluation of the prognostic potential of EGFL7 in pilocytic astrocytomas. NEUROPATHOLOGY, v. 41, n. 1, p. 8-pg., . (16/21727-4, 16/23919-8, 17/09749-5, 12/19590-0)
CRUVINEL-CARLONI, ADRIANA; SILVA-OLIVEIRA, RENATO; TORRIERI, RAUL; BIDINOTTO, LUCAS TADEU; BERARDINELLI, GUSTAVO NORIZ; OLIVEIRA-SILVA, VIVIANE ALINE; CLARA, CARLOS AFONSO; DE ALMEIDA, GISELE CARAVINA; MARTINHO, OLGA; SQUIRE, JEREMY ANDREW; et al. Molecular characterization of short-term primary cultures and comparison with corresponding tumor tissue of Brazilian glioblastoma patients. TRANSLATIONAL CANCER RESEARCH, v. 6, n. 2, p. 332+, . (11/08523-7, 12/08287-4, 12/19590-0)
VIANA-PEREIRA, MARTA; ALMEIDA, GISELE CARAVINA; STAVALE, JOAO NORBERTO; MALHEIRO, SUSANA; CLARA, CARLOS; LOBO, PATRICIA; PIMENTEL, JOSE; REIS, RUI MANUEL. Study of hTERT and Histone 3 Mutations in Medulloblastoma. PATHOBIOLOGY, v. 84, n. 2, p. 108-113, . (12/19590-0)
BATISTA, RUI; CRUVINEL-CARLONI, ADRIANA; VINAGRE, JOAO; PEIXOTO, JOANA; CATARINO, TELMO A.; CAMPANELLA, NATHALIA CRISTINA; MENEZES, WEDER; BECKER, ALINE PAIXAO; DE ALMEIDA, GISELE CARAVINA; MATSUSHITA, MARCUS M.; et al. The prognostic impact of TERT promoter mutations in glioblastomas is modified by the rs2853669 single nucleotide polymorphism. International Journal of Cancer, v. 139, n. 2, p. 414-423, . (12/19590-0, 13/25787-3)
BIDINOTTO, LUCAS TADEU; SCAPULATEMPO-NETO, CRISTOVAM; MACKAY, ALAN; DE ALMEIDA, GISELE CARAVINA; SCHEITHAUER, BERND WALTER; BERARDINELLI, GUSTAVO NORIZ; TORRIERI, RAUL; CLARA, CARLOS AFONSO; FELTRIN, LEONIR TEREZINHA; VIANA-PEREIRA, MARTA; et al. Molecular Profiling of a Rare Rosette-Forming Glioneuronal Tumor Arising in the Spinal Cord. PLoS One, v. 10, n. 9, . (11/08523-7, 12/08287-4, 12/19590-0)
BECKER, ALINE PAIXAO; SCAPULATEMPO-NETO, CRISTOVAM; CARLONI, ADRIANA C.; PAULINO, ALESSANDRA; SHEREN, JAMIE; AISNER, DARA L.; MUSSELWHITE, EVELYN; CLARA, CARLOS; MACHADO, HELIO R.; OLIVEIRA, RICARDO S.; et al. KIAA1549: BRAF Gene Fusion and FGFR1 Hotspot Mutations Are Prognostic Factors in Pilocytic Astrocytomas. JOURNAL OF NEUROPATHOLOGY AND EXPERIMENTAL NEUROLOGY, v. 74, n. 7, p. 743-754, . (12/19590-0)
BECKER, ALINE PAIXAO; SCAPULATEMPO-NETO, CRISTOVAM; MENEZES, WEDER P.; CLARA, CARLOS; MACHADO, HELIO R.; OLIVEIRA, RICARDO S.; NEDER, LUCIANO; REIS, RUI MANUEL. Expression of Methylthioadenosine Phosphorylase (MTAP) in Pilocytic Astrocytomas. PATHOBIOLOGY, v. 82, n. 2, p. 84-89, . (12/19590-0)
PINTO, FILIPE; COSTA, ANGELA M.; ANDRADE, RAQUEL P.; REIS, RUI MANUEL. Brachyury Is Associated with Glioma Differentiation and Response to Temozolomide. NEUROTHERAPEUTICS, v. 17, n. 4, SI, . (12/19590-0)
PINTO, FILIPE; COSTA, ANGELA M.; SANTOS, GISELE C.; MATSUSHITA, MARCUS M.; COSTA, SANDRA; SILVA, VIVIANE A. O.; MIRANDA-GONCALVES, VERA; LOPES, CELESTE M.; CLARA, CARLOS A.; BECKER, ALINE P.; et al. The T-box transcription factor brachyury behaves as a tumor suppressor in gliomas. JOURNAL OF PATHOLOGY, v. 251, n. 1, . (12/19590-0)
BRUNHARA, BRUNO B.; BECKER, ALINE P.; NEDER, LUCIANO; GONCALVES, PAOLA G.; DE OLIVEIRA, CRISTIANE; CLARA, CARLOS A.; REIS, RUI M.; BIDINOTTO, LUCAS T.. Evaluation of the prognostic potential of EGFL7 in pilocytic astrocytomas. NEUROPATHOLOGY, . (16/23919-8, 12/19590-0, 17/09749-5, 16/21727-4)
BIDINOTTO, LUCAS TADEU; TORRIERI, RAUL; MACKAY, ALAN; ALMEIDA, GISELE CARAVINA; VIANA-PEREIRA, MARTA; CRUVINEL-CARLONI, ADRIANA; SPINA, MARIA LUISA; CAMPANELLA, NATHALIA CRISTINA; DE MENEZES, WEDER PEREIRA; CLARA, CARLOS AFONSO; et al. Copy Number Profiling of Brazilian Astrocytomas. G3-GENES, GENOMES, GENETICS, v. 6, n. 7, p. 1867-1878, . (12/08287-4, 11/08523-7, 12/19590-0, 13/25787-3)
BATISTA, RUI; CRUVINEL-CARLONI, ADRIANA; VINAGRE, JOAO; PEIXOTO, JOANA; CATARINO, TELMO A.; CAMPANELLA, NATHALIA CRISTINA; MENEZES, WEDER; BECKER, ALINE PAIXAO; DE ALMEIDA, GISELE CARAVINA; MATSUSHITA, MARCUS M.; et al. The prognostic impact of TERT promoter mutations in glioblastomas is modified by the rs2853669 single nucleotide polymorphism. International Journal of Cancer, v. 139, n. 2, p. 10-pg., . (13/25787-3, 12/19590-0)

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