Molecular characterization of short-term primary cultures and comparison with corresponding tumor tissue of Brazilian glioblastoma patients

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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 ; Reis, Rui Manuel

• Tipo de documento: Artigo Científico
• Fonte: TRANSLATIONAL CANCER RESEARCH; v. 6, n. 2, p. 332+, APR 2017.
• Citações Web of Science: 4

Resumo

Background: Glioblastoma, the most frequent and malignant adult brain tumor, has been extensively studied. However, there is no effective treatment, and to overcome this challenging scenario, it is essential to improve preclinical biological models. This study aimed to molecularly characterize short-term glioblastoma primary cultures and to compare them with patient tumor profiles. Methods: Glioblastoma cell lines were established from Barretos Cancer Hospital patients diagnosed with glioblastoma. The cells were cultured with DMEM (+)10% FBS (+)1% PS and were molecularly characterized using array CGH (aCGH), next-generation and Sanger sequencing. Results: We established four short-term glioblastoma cultures and we found that the primary cells exhibited a diversity of chromosomal aberrations, with gain of chromosome 7 and loss of chromosomes 10, 13 and 17p being the most frequent alterations. Mutation profiling showed that hotspot TERT promoter mutations were present in 3/4 cases, followed by mutations in TP53 (2/4) and in the RB1, BRAF and PTEN (1/4) genes. A similar chromosomal and mutation pattern was observed in all short-term cultures and matched frozen tumors. Conclusions: Herein, short-term glioblastoma primary cultures were successfully characterized and had genetic make-ups that were similar to those of patient tumors, suggesting that short-term primary cultures are suitable in vitro models for studies of glioblastoma biology. (AU)

• Processo FAPESP: 11/08523-7 - Perfil de alterações cromossômicas em tumores cerebrais (meduloblastomas e gliomas): impacto na identificação de novas vias tumorigênicas
• Beneficiário: Lucas Tadeu Bidinotto
• Modalidade de apoio: Bolsas no Brasil - Pós-Doutorado
• Processo FAPESP: 12/08287-4 - Perfil de alterações cromossômicas em gliomas
• Beneficiário: Lucas Tadeu Bidinotto
• Modalidade de apoio: Bolsas no Exterior - Estágio de Pesquisa - Pós-Doutorado
• Processo FAPESP: 12/19590-0 - Perfil mutacional de linhagens primárias de glioblastomas
• Beneficiário: Rui Manuel Vieira Reis
• Modalidade de apoio: Auxílio à Pesquisa - Regular