The ten-year evolutionary trajectory of a highly recurrent paediatric high grade neuroepithelial tumour with MN1:BEND2 fusion

Anna Burford, Alan Mackay, Sergey Popov, Maria Vinci, Diana Carvalho, Matthew Clarke, Elisa Izquierdo, Aimee Avery, Thomas S Jacques, Wendy J Ingram, Andrew S Moore, Kieran Frawley, Timothy E Hassall, Thomas Robertson, Chris Jones

Research output: Contribution to journalArticle

Abstract

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.

Original languageEnglish
Pages (from-to)1032
Number of pages10
JournalScientific Reports
Volume8
Issue number1
DOIs
Publication statusPublished - Jan 18 2018

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Neuroepithelial Neoplasms
Pediatrics
Brain Neoplasms
Exome
Neoplasms
Gene Targeting
Gene Fusion
Glioma
Methylation
Disease Progression
Young Adult
History
Genome
Recurrence
Therapeutics

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The ten-year evolutionary trajectory of a highly recurrent paediatric high grade neuroepithelial tumour with MN1:BEND2 fusion. / Burford, Anna; Mackay, Alan; Popov, Sergey; Vinci, Maria; Carvalho, Diana; Clarke, Matthew; Izquierdo, Elisa; Avery, Aimee; Jacques, Thomas S; Ingram, Wendy J; Moore, Andrew S; Frawley, Kieran; Hassall, Timothy E; Robertson, Thomas; Jones, Chris.

In: Scientific Reports, Vol. 8, No. 1, 18.01.2018, p. 1032.

Research output: Contribution to journalArticle

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 2018, 'The ten-year evolutionary trajectory of a highly recurrent paediatric high grade neuroepithelial tumour with MN1:BEND2 fusion', Scientific Reports, vol. 8, no. 1, pp. 1032. https://doi.org/10.1038/s41598-018-19389-9
Burford, Anna ; Mackay, Alan ; Popov, Sergey ; Vinci, Maria ; Carvalho, Diana ; Clarke, Matthew ; Izquierdo, Elisa ; Avery, Aimee ; Jacques, Thomas S ; Ingram, Wendy J ; Moore, Andrew S ; Frawley, Kieran ; Hassall, Timothy E ; Robertson, Thomas ; Jones, Chris. / The ten-year evolutionary trajectory of a highly recurrent paediatric high grade neuroepithelial tumour with MN1:BEND2 fusion. In: Scientific Reports. 2018 ; Vol. 8, No. 1. pp. 1032.
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