Identification of novel fusion transcripts in meningioma.

TitleIdentification of novel fusion transcripts in meningioma.
Publication TypeJournal Article
Year of Publication2020
AuthorsA Khan, B, Gadot, R, Shetty, A, Bayley, JC, Hadley, CC, Cardenas, MF, Jalali, A, Harmanci, AS, Harmanci, AO, Wheeler, DA, Klisch, TJ, Patel, AJ
JournalJ Neurooncol
Volume149
Issue2
Pagination219-230
Date Published2020 Sep
ISSN1573-7373
KeywordsAdult, Aged, Biomarkers, Tumor, Cohort Studies, Female, Follow-Up Studies, High-Throughput Nucleotide Sequencing, Humans, Male, Meningeal Neoplasms, Meningioma, Middle Aged, Mutation, Oncogene Proteins, Fusion, Prognosis
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.

DOI10.1007/s11060-020-03599-1
Alternate JournalJ Neurooncol
PubMed ID32949309
PubMed Central IDPMC7553203
Grant ListK08 NS102474 / NS / NINDS NIH HHS / United States
P30 CA125123 / CA / NCI NIH HHS / United States
K08NS102474 / NS / NINDS NIH HHS / United States
CA125123 / CA / NCI NIH HHS / United States