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 journalArticlepeer-review

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

Fingerprint

Dive into the research topics of 'The ten-year evolutionary trajectory of a highly recurrent paediatric high grade neuroepithelial tumour with MN1:BEND2 fusion'. Together they form a unique fingerprint.

Cite this