Prognostic significance of telomerase reverse transcriptase promoter gen mutations in high grade meningiomas

Alejandro Cañas , Enrique Jiménez , Fernando Hakim , Juan Armando Mejía , Juan Fernando Ramón , Diego Gómez , Daniel Jaramillo-Velásquez , Sonia Bermúdez , Nicolás Useche , Diego Pineda , Hernando Cifuentes , Antonio Becerra, Álvaro Muñoz , Nicolás Santoyo , Alejandro Ruíz-Patiño , Carolina Sotelo , Pilar Archila , July Rodríguez , Jenny Ávila , Camila Ordoñez-Reyes, Juan Esteban García-Robledo , Luisa Ricaurte , Leonardo Rojas , Oscar Feo , Remberto Burgos , Carlos Ramírez , Oscar Arrieta , Lucía Zatarain-Barrón , Carlos Vargas , Hernán Carranza , Jorge Otero , Andrés F. Cardona , .

DOI: https://doi.org/10.7705/biomedica.6100
Keywords: Meningioma, gain-of-function mutation, telomerase
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Abstract

Introduction: Mutations in the promoter region of telomerase reverse transcriptase occur frequently in meningiomas.
Objective: To estimate the prognostic importance of telomerase reverse transcriptase mutations in Colombian patients with grades II and III meningioma.
Materials and methods: This was a multicenter retrospective cohort study of patients diagnosed with refractory or recurrent WHO grades II and III meningiomas, recruited between 2011 and 2018, and treated with systemic therapy (sunitinib, everolimus ± octreotide, and bevacizumab). Mutation status of the telomerase reverse transcriptase promoter was established by PCR.
Results: Forty patients were included, of which telomerase reverse transcriptase mutations were found in 21 (52.5%), being C228T and C250T the most frequent variants with 87.5 % and 14.3 %, respectively. These were more frequent among patients with anaplastic meningiomas (p=0.18), with more than 2 recurrences (p=0.04); and in patients with parasagittal region and anterior fossa lesions (p=0.05). Subjects characterized as having punctual mutations were more frequently administered with everolimus, sunitinib and bevacizumab drug series (p=0.06). Overall survival was 23.7 months (CI95% 13.1-34.2) and 43.4 months (CI95% 37.5-49.3; p=0.0001) between subjects with and without mutations, respectively. Multivariate analysis showed that the number of recurrences and the presence of telomerase reverse transcriptase mutations were tthe only variables that negatively affected overall survival.
Conclusions: Mutations in telomerase reverse transcriptase allows the identification of high-risk patients and could be useful in the selection of the best medical treatment.

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  • Alejandro Cañas Departamento de Neurocirugía, Fundación Santa Fe de Bogotá, Bogotá, D. C., Colombia
  • Enrique Jiménez Departamento de Neurocirugía, Fundación Santa Fe de Bogotá, Bogotá, D. C., Colombia
  • Fernando Hakim Departamento de Neurocirugía, Fundación Santa Fe de Bogotá, Bogotá, D. C., Colombia
  • Juan Armando Mejía Departamento de Neurocirugía, Fundación Santa Fe de Bogotá, Bogotá, D. C., Colombia
  • Juan Fernando Ramón Departamento de Neurocirugía, Fundación Santa Fe de Bogotá, Bogotá, D. C., Colombia
  • Diego Gómez Departamento de Neurocirugía, Fundación Santa Fe de Bogotá, Bogotá, D. C., Colombia
  • Daniel Jaramillo-Velásquez Departamento de Neurocirugía, Fundación Santa Fe de Bogotá, Bogotá, D. C., Colombia
  • Sonia Bermúdez Departamento de Imágenes Diagnósticas, Sección Neuro-radiología, Fundación Santa Fe de Bogotá, Bogotá, D. C., Colombia
  • Nicolás Useche Departamento de Imágenes Diagnósticas, Sección Neuro-radiología, Fundación Santa Fe de Bogotá, Bogotá, D. C., Colombia
  • Diego Pineda Departamento de Radiología, Sección Neuro-radiología, Clínica del Country, , Bogotá, D. C., Colombia
  • Hernando Cifuentes Departamento de Neurocirugía, Clínica del Country, Bogotá, D. C., Colombia
  • Antonio Becerra Departamento de Neurocirugía, Clínica Colsanitas, Bogotá, D. C., Colombia
  • Álvaro Muñoz Departamento de Radio-oncología, Instituto de Cáncer Carlos Ardila Lülle, Fundación Santa Fe de Bogotá, Bogotá, D. C., Colombia
  • Nicolás Santoyo Fundación para la Investigación Clínica y Molecular Aplicada del Cáncer, Bogotá, D. C., Colombia; Grupo de Investigación en Oncología Molecular y Sistemas Biológicos, Universidad El Bosque, Bogotá, D. C., Colombia
  • Alejandro Ruíz-Patiño Fundación para la Investigación Clínica y Molecular Aplicada del Cáncer, Bogotá, D. C., Colombia; Grupo de Investigación en Oncología Molecular y Sistemas Biológicos, Universidad El Bosque, Bogotá, D. C., Colombia
  • Carolina Sotelo Fundación para la Investigación Clínica y Molecular Aplicada del Cáncer, Bogotá, D. C., Colombia; Grupo de Investigación en Oncología Molecular y Sistemas Biológicos, Universidad El Bosque, Bogotá, D. C., Colombia
  • Pilar Archila Fundación para la Investigación Clínica y Molecular Aplicada del Cáncer, Bogotá, D. C., Colombia; Grupo de Investigación en Oncología Molecular y Sistemas Biológicos, Universidad El Bosque, Bogotá, D. C., Colombia
  • July Rodríguez Fundación para la Investigación Clínica y Molecular Aplicada del Cáncer, Bogotá, D. C., Colombia; Grupo de Investigación en Oncología Molecular y Sistemas Biológicos, Universidad El Bosque, Bogotá, D. C., Colombia
  • Jenny Ávila Fundación para la Investigación Clínica y Molecular Aplicada del Cáncer, Bogotá, D. C., Colombia; Grupo de Investigación en Oncología Molecular y Sistemas Biológicos, Universidad El Bosque, Bogotá, D. C., Colombia
  • Camila Ordoñez-Reyes Fundación para la Investigación Clínica y Molecular Aplicada del Cáncer, Bogotá, D. C., Colombia; Grupo de Investigación en Oncología Molecular y Sistemas Biológicos, Universidad El Bosque, Bogotá, D. C., Colombia
  • Juan Esteban García-Robledo Grupo de Investigación en Oncología Molecular y Sistemas Biológicos, Universidad El Bosque, Bogotá, D. C., Colombia; División de Hematología y Oncología, Clínica Mayo, Scottsdale, Estados Unidos
  • Luisa Ricaurte Fundación para la Investigación Clínica y Molecular Aplicada del Cáncer, Bogotá, D. C., Colombia; Grupo de Investigación en Oncología Molecular y Sistemas Biológicos, Universidad El Bosque, Bogotá, D. C., Colombia; Departamento de Patología, Clínica Mayo, Rochester, Estados Unidos
  • Leonardo Rojas Grupo de Investigación en Oncología Molecular y Sistemas Biológicos, Universidad El Bosque, Bogotá, D. C., Colombia; Departamento de Oncología Clínica, Clínica Colsanitas, Bogotá, Colombia; Grupo Oncología Clínica y Traslacional, Clínica del Country, Bogotá, Colombia
  • Oscar Feo Departamento de Neurocirugía, Clínica Colsanitas, Bogotá, D. C., Colombia
  • Remberto Burgos Departamento de Neurocirugía, Clínica Colsanitas, Bogotá, D. C., Colombia
  • Carlos Ramírez Departamento de Neurocirugía, Clínica Colsanitas, Bogotá, D. C., Colombia
  • Oscar Arrieta Laboratorio Oncología Personalizada, Instituto Nacional de Cancerología, Ciudad de México, México
  • Lucía Zatarain-Barrón Laboratorio Oncología Personalizada, Instituto Nacional de Cancerología, Ciudad de México, México
  • Carlos Vargas Fundación para la Investigación Clínica y Molecular Aplicada del Cáncer, Bogotá, D. C., Colombia; Grupo de Investigación en Oncología Molecular y Sistemas Biológicos, Universidad El Bosque, Bogotá, D. C., Colombia; Departamento de Oncología Clínica, Clínica Colsanitas, Bogotá, Colombia
  • Hernán Carranza Fundación para la Investigación Clínica y Molecular Aplicada del Cáncer, Bogotá, D. C., Colombia; Grupo de Investigación en Oncología Molecular y Sistemas Biológicos, Universidad El Bosque, Bogotá, D. C., Colombia; Departamento de Oncología Clínica, Clínica Colsanitas, Bogotá, Colombia
  • Jorge Otero Fundación para la Investigación Clínica y Molecular Aplicada del Cáncer, Bogotá, D. C., Colombia; Grupo de Investigación en Oncología Molecular y Sistemas Biológicos, Universidad El Bosque, Bogotá, D. C., Colombia; Departamento de Oncología Clínica, Clínica Colsanitas, Bogotá, Colombia
  • Andrés F. Cardona Fundación para la Investigación Clínica y Molecular Aplicada del Cáncer, Bogotá, D. C., Colombia; Grupo de Investigación en Oncología Molecular y Sistemas Biológicos, Universidad El Bosque, Bogotá, D. C., Colombia; Departamento de Oncología Clínica, Clínica Colsanitas, Bogotá, Colombia

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How to Cite
1.
Cañas A, Jiménez E, Hakim F, Mejía JA, Ramón JF, Gómez D, et al. Prognostic significance of telomerase reverse transcriptase promoter gen mutations in high grade meningiomas. Biomed. [Internet]. 2022 Dec. 1 [cited 2025 Apr. 4];42(4):574-90. Available from: https://revistabiomedicaorg.biteca.online/index.php/biomedica/article/view/6100

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Published
2022-12-01
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Vol. 42 No. 4 (2022)
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Original articles

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