The ten-year evolutionary trajectory of a highly recurrent paediatric high grade neuroepithelial tumour with MN1:BEND2 fusion.
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Date
2018-01-18Author
Burford, A
Mackay, A
Popov, S
Vinci, M
Carvalho, D
Clarke, M
Izquierdo, E
Avery, A
Jacques, TS
Ingram, WJ
Moore, AS
Frawley, K
Hassall, TE
Robertson, T
Jones, C
Type
Journal Article
Metadata
Show full item recordAbstract
Astroblastomas are rare brain tumours which predominate in children and young adults, and have a controversial claim as a distinct entity, with no established WHO grade. Reports suggest a better outcome than high grade gliomas, though they frequently recur. Recently, they have been described to overlap with a newly-discovered group of tumours described as'high grade neuroepithelial tumour with MN1 alteration' (CNS HGNET-MN1), defined by global methylation patterns and strongly associated with gene fusions targeting MN1. We have studied a unique case of astroblastoma arising in a 6 year-old girl, with multiple recurrences over a period of 10 years, with the pathognomonic MN1:BEND2 fusion. Exome sequencing allowed for a phylogenetic reconstruction of tumour evolution, which when integrated with clinical, pathological and radiological data provide for a detailed understanding of disease progression, with initial treatment driving tumour dissemination along four distinct trajectories. Infiltration of distant sites was associated with a later genome doubling, whilst there was evidence of convergent evolution of different lesions acquiring distinct alterations targeting NF-κB. These data represent an unusual opportunity to understand the evolutionary history of a highly recurrent childhood brain tumour, and provide novel therapeutic targets for astroblastoma/CNS HGNET-MN1.
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Subject
Humans
Neoplasms, Neuroepithelial
Translocation, Genetic
Recurrence
Trans-Activators
Oncogene Proteins, Fusion
Tumor Suppressor Proteins
Immunohistochemistry
In Situ Hybridization, Fluorescence
Age Factors
Child
Female
Neoplasm Grading
Whole Exome Sequencing
Research team
Glioma Team
Language
eng
Date accepted
2017-12-29
License start date
2018-01-18
Citation
Scientific reports, 2018, 8 (1), pp. 1032 - ?
Publisher
Springer Science and Business Media LLC