Identification of novel fusion transcripts in meningioma.

Khan, A Basit; Gadot, Ron; Shetty, Arya; Bayley, James C; Hadley, Caroline C; Cardenas, Maria F; Jalali, Ali; Harmanci, Akdes S; Harmanci, Arif O; Wheeler, David A; Klisch, Tiemo J; Patel, Akash J

Khan, A Basit; Gadot, Ron; Shetty, Arya; Bayley, James C; Hadley, Caroline C; Cardenas, Maria F; Jalali, Ali; Harmanci, Akdes S; Harmanci, Arif O; Wheeler, David A; Klisch, Tiemo J; Patel, Akash J.

Afiliación

Khan AB; Department of Neurosurgery, Baylor College of Medicine, 7200 Cambridge 9th Floor, Houston, TX, 77030, USA.
Gadot R; Department of Neurosurgery, Baylor College of Medicine, 7200 Cambridge 9th Floor, Houston, TX, 77030, USA.
Shetty A; Department of Neurosurgery, Baylor College of Medicine, 7200 Cambridge 9th Floor, Houston, TX, 77030, USA.
Bayley JC; Department of Neurosurgery, Baylor College of Medicine, 7200 Cambridge 9th Floor, Houston, TX, 77030, USA.
Hadley CC; Department of Neurosurgery, Baylor College of Medicine, 7200 Cambridge 9th Floor, Houston, TX, 77030, USA.
Cardenas MF; Department of Molecular and Human Genetics, Human Genome Sequencing Center, Baylor College of Medicine, Houston, TX, 77030, USA.
Jalali A; Department of Neurosurgery, Baylor College of Medicine, 7200 Cambridge 9th Floor, Houston, TX, 77030, USA.
Harmanci AS; School of Biomedical Informatics, Center for Computational Systems Medicine, University of Texas Health Science Center At Houston, Houston, TX, 77030, USA.
Harmanci AO; School of Biomedical Informatics, Center for Computational Systems Medicine, University of Texas Health Science Center At Houston, Houston, TX, 77030, USA.
Wheeler DA; Department of Molecular and Human Genetics, Human Genome Sequencing Center, Baylor College of Medicine, Houston, TX, 77030, USA.
Klisch TJ; Texas Children's Hospital, Jan and Dan Duncan Neurological Research Institute, Houston, TX, 77030, USA. klisch@bcm.edu.
Patel AJ; Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX, 77030, USA. klisch@bcm.edu.

J Neurooncol ; 149(2): 219-230, 2020 Sep.

Article en En | MEDLINE | ID: mdl-32949309

RESUMEN

INTRODUCTION: Meningiomas are the most common primary intracranial tumor. Recent next generation sequencing analyses have elaborated the molecular drivers of this disease. We aimed to identify and characterize novel fusion genes in meningiomas. METHODS: We performed a secondary analysis of our RNA sequencing data of 145 primary meningioma from 140 patients to detect fusion genes. Semi-quantitative rt-PCR was performed to confirm transcription of the fusion genes in the original tumors. Whole exome sequencing was performed to identify copy number variations within each tumor sample. Comparative RNA seq analysis was performed to assess the clonality of the fusion constructs within the tumor. RESULTS: We detected six fusion events (NOTCH3-SETBP1, NF2-SPATA13, SLC6A3-AGBL3, PHF19-FOXP2 in two patients, and ITPK1-FBP2) in five out of 145 tumor samples. All but one event (NF2-SPATA13) led to extremely short reading frames, making these events de facto null alleles. Three of the five patients had a history of childhood radiation. Four out of six fusion events were detected in expression type C tumors, which represent the most aggressive meningioma. We validated the presence of the RNA transcripts in the tumor tissue by semi-quantitative RT PCR. All but the two PHF19-FOXP2 fusions demonstrated high degrees of clonality. CONCLUSIONS: Fusion genes occur infrequently in meningiomas and are more likely to be found in tumors with greater degree of genomic instability (expression type C) or in patients with history of cranial irradiation.

Asunto(s)

Biomarcadores de Tumor/genética; Neoplasias Meníngeas/genética; Meningioma/genética; Mutación; Proteínas de Fusión Oncogénica/genética; Adulto; Anciano; Estudios de Cohortes; Femenino; Estudios de Seguimiento; Secuenciación de Nucleótidos de Alto Rendimiento; Humanos; Masculino; Neoplasias Meníngeas/patología; Meningioma/patología; Persona de Mediana Edad; Pronóstico

Palabras clave

Fusion gene; Meningioma; NF2; RNA sequencing

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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Biomarcadores de Tumor / Proteínas de Fusión Oncogénica / Neoplasias Meníngeas / Meningioma / Mutación Tipo de estudio: Diagnostic_studies / Etiology_studies / Incidence_studies / Observational_studies / Prognostic_studies / Risk_factors_studies Límite: Adult / Aged / Female / Humans / Male / Middle aged Idioma: En Revista: J Neurooncol Año: 2020 Tipo del documento: Article País de afiliación: Estados Unidos Pais de publicación: Estados Unidos

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