The ten-year evolutionary trajectory of a highly recurrent paediatric high grade neuroepithelial tumour with MN1:BEND2 fusion.
Anna BurfordAlan MackaySergey PopovMaria VinciDiana CarvalhoMatthew ClarkeElisa IzquierdoAimee AveryThomas S JacquesWendy J IngramAndrew S MooreKieran FrawleyTimothy E HassallThomas RobertsonChris JonesPublished in: Scientific reports (2018)
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.
Keyphrases
- high grade
- low grade
- young adults
- genome wide
- room temperature
- transition metal
- metal organic framework
- blood brain barrier
- emergency department
- intensive care unit
- electronic health record
- white matter
- oxidative stress
- resting state
- signaling pathway
- depressive symptoms
- cancer therapy
- dna methylation
- inflammatory response
- lymph node
- big data
- machine learning
- multiple sclerosis
- single cell
- drug delivery
- childhood cancer
- transcription factor
- nuclear factor
- early life