Identification of Novel Fusion Transcripts in Meningioma. (16th November 2020)

• Record Type: Journal Article
• Authors: Khan, Abdul B; Gadot, Ron; Shetty, Arya; Bayley, James; Hadley, Caroline; Cardenas, Maria; Jalali, Ali; Harmanci, Akdes; Harmanci, Arif; Wheeler, David; Klisch, Tiemo; Patel, Akash J
• Is Part Of: Neurosurgery. Volume 67(2010)Supplement 1
• Publication Date: 2020-11-16
• Subjects: Nervous system -- Surgery -- Periodicals; 617.48005
• DOI: 10.1093/neuros/nyaa447_852
• Languages: English
• ISSNs: 0148-396X

Abstract

Abstract: INTRODUCTION: Meningiomas are the most common primary intracranial tumor. Our recent transcription based classification identified three categories of meningioma (A, B, C) with progressively worse clinical outcomes. 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 (CNV) within each tumor sample. RESULTS: We detected six fusion events (NOTCH3-SETBP1, NF2-SPATA13, SLC6A3-AGBL3, ITPK1-FBP2, and PHF19-FOXP2 in two patients) in five out of 145 tumor samples. All but one event (NF2-SPATA13) led to truncated reading frames, rendering these de facto null alleles. The fusion genes were all inter-chromosomal fusions occurring between genes on separate, non-homologous chromosomes. We performed whole exome sequencing and have summarized the CNV data. Four patients had type C tumors, which represent the most aggressive meningioma. The four type C tumors had an average arm-level chromosome loss of 9 (range 7–13) and an average arm-level chromosome gain of 1.3 (range 0–4) whereas the single type B tumor showed only loss of chromosome 22q, and no copy number gains. We validated the presence of the RNA transcripts in the tumor tissue by semi-quantitative RT PCR. Three of the five patients had a history of childhood radiation. The median age of patients was 48 years (range 42–70 years). Four patients underwent gross total resection, while one had a subtotal resection. Tumor size ranged from 0.8 to 4.5cm in maximum dimension. The median MIB1 was 5.7% (range 3–40%). CONCLUSION: Fusion genes occur infrequently in meningioma 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.