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Identification of novel fusion transcripts in meningioma

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Abstract

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.

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Funding

Parts of this study were funded by the Roderick D. MacDonald Fund, the Jan and Dan Duncan Neurologic Research Institute at Texas Children’s Hospital, and the Hamill Foundation. A.J.P. is supported by a K08 award by the National Institute of Neurological Disorders and Stroke (K08NS102474). The Human Tissue Acquisition and Pathology Core at Baylor College of Medicine is funded through P30 Cancer Center Support Grant NCI-CA125123.

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Author notes

  1. Tiemo J. Klisch and Akash J. Patel have contributed equally to this work.

Authors and Affiliations

  1. Department of Neurosurgery, Baylor College of Medicine, 7200 Cambridge 9th Floor, Houston, TX, 77030, USA

    A. Basit Khan, Ron Gadot, Arya Shetty, James C. Bayley V, Caroline C. Hadley, Ali Jalali & Akash J. Patel

  2. Department of Molecular and Human Genetics, Human Genome Sequencing Center, Baylor College of Medicine, Houston, TX, 77030, USA

    Maria F. Cardenas & David A. Wheeler

  3. School of Biomedical Informatics, Center for Computational Systems Medicine, University of Texas Health Science Center At Houston, Houston, TX, 77030, USA

    Akdes S. Harmanci & Arif O. Harmanci

  4. Texas Children’s Hospital, Jan and Dan Duncan Neurological Research Institute, Houston, TX, 77030, USA

    Tiemo J. Klisch & Akash J. Patel

  5. Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX, 77030, USA

    Tiemo J. Klisch

  6. Department of Otolaryngology-Head and Neck Surgery, Baylor College of Medicine, Houston, TX, USA

    Akash J. Patel

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  1. A. Basit Khan
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Contributions

ABK., TJK, and AJP designed the research. ABK, RG, AS, CCH, JCBV, MC, DAW, TJK, and AJP performed the research. ABK, MC, ASH, AOH, DAW, TJK, and AJP. analyzed the data. ABK, TJK, DAW, and AJP wrote the paper.

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Correspondence to Tiemo J. Klisch or Akash J. Patel.

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Khan, A.B., Gadot, R., Shetty, A. et al. Identification of novel fusion transcripts in meningioma. J Neurooncol 149, 219–230 (2020). https://doi.org/10.1007/s11060-020-03599-1

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