Please use this identifier to cite or link to this item: http://hdl.handle.net/1822/29193

TitleThe prognostic role of intragenic copy number breakpoints and identification of novel fusion genes in paediatric high grade glioma
Author(s)Carvalho, Diana
Mackay, Alan
Bjerke, Lynn
Grundy, Richard G.
Lopes, Celeste
Reis, R. M.
Jones, Chris
KeywordsFusion
Paediatric
Glioblastoma
Copy number
Intragenic
Issue date2014
PublisherBioMed Central
JournalActa Neuropathologica Communications
Abstract(s)BACKGROUND: Paediatric high grade glioma (pHGG) is a distinct biological entity to histologically similar tumours arising in older adults, and has differing copy number profiles and driver genetic alterations. As functionally important intragenic copy number aberrations (iCNA) and fusion genes begin to be identified in adult HGG, the same has not yet been done in the childhood setting. We applied an iCNA algorithm to our previously published dataset of DNA copy number profiling in pHGG with a view to identify novel intragenic breakpoints. RESULTS: We report a series of 288 iCNA events in pHGG, with the presence of intragenic breakpoints itself a negative prognostic factor. We identified an increased number of iCNA in older children compared to infants, and increased iCNA in H3F3A K27M mutant tumours compared to G34R/V and wild-type. We observed numerous gene disruptions by iCNA due to both deletions and amplifications, targeting known HGG-associated genes such as RB1 and NF1, putative tumour suppressors such as FAF1 and KIDINS220, and novel candidates such as PTPRE and KCND2. We further identified two novel fusion genes in pHGG - CSGALNACT2:RET and the complex fusion DHX57:TMEM178:MAP4K3. The latter was sequence-validated and appears to be an activating event in pHGG. CONCLUSIONS: These data expand upon our understanding of the genomic events driving these tumours and represent novel targets for therapeutic intervention in these poor prognosis cancers of childhood.
TypeArticle
URIhttp://hdl.handle.net/1822/29193
DOI10.1186/2051-5960-2-23
ISSN2051-5960
Publisher versionhttp://www.actaneurocomms.org/content/2/1/23
Peer-Reviewedyes
AccessOpen access
Appears in Collections:ICVS - Artigos em Revistas Internacionais com Referee

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