The prognostic role of intragenic copy number breakpoints and identification of novel fusion genes in paediatric high grade glioma
Autor(a) principal: | |
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Data de Publicação: | 2014 |
Outros Autores: | , , , , , |
Tipo de documento: | Artigo |
Idioma: | eng |
Título da fonte: | Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) |
Texto Completo: | http://hdl.handle.net/10316/109353 https://doi.org/10.1186/2051-5960-2-23 |
Resumo: | 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. |
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Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) |
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7160 |
spelling |
The prognostic role of intragenic copy number breakpoints and identification of novel fusion genes in paediatric high grade gliomaFusionPaediatricGlioblastomaCopy numberIntragenicAlgorithmsBrain NeoplasmsChildChild, PreschoolFemaleGene DeletionGene Expression ProfilingGliomaHumansInfantMaleN-AcetylgalactosaminyltransferasesOligonucleotide Array Sequence AnalysisOncogene Proteins, FusionRNA, Small InterferingChromosome BreakageDNA Copy Number VariationsBackground: 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.Springer Nature2014-02-18info:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articlehttp://hdl.handle.net/10316/109353http://hdl.handle.net/10316/109353https://doi.org/10.1186/2051-5960-2-23eng2051-5960Carvalho, DianaMackay, AlanBjerke, LynnGrundy, Richard G.Lopes, CelesteReis, Rui M.Jones, Chrisinfo:eu-repo/semantics/openAccessreponame:Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)instname:Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informaçãoinstacron:RCAAP2023-10-11T08:11:52Zoai:estudogeral.uc.pt:10316/109353Portal AgregadorONGhttps://www.rcaap.pt/oai/openaireopendoar:71602024-03-19T21:25:33.316655Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) - Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informaçãofalse |
dc.title.none.fl_str_mv |
The prognostic role of intragenic copy number breakpoints and identification of novel fusion genes in paediatric high grade glioma |
title |
The prognostic role of intragenic copy number breakpoints and identification of novel fusion genes in paediatric high grade glioma |
spellingShingle |
The prognostic role of intragenic copy number breakpoints and identification of novel fusion genes in paediatric high grade glioma Carvalho, Diana Fusion Paediatric Glioblastoma Copy number Intragenic Algorithms Brain Neoplasms Child Child, Preschool Female Gene Deletion Gene Expression Profiling Glioma Humans Infant Male N-Acetylgalactosaminyltransferases Oligonucleotide Array Sequence Analysis Oncogene Proteins, Fusion RNA, Small Interfering Chromosome Breakage DNA Copy Number Variations |
title_short |
The prognostic role of intragenic copy number breakpoints and identification of novel fusion genes in paediatric high grade glioma |
title_full |
The prognostic role of intragenic copy number breakpoints and identification of novel fusion genes in paediatric high grade glioma |
title_fullStr |
The prognostic role of intragenic copy number breakpoints and identification of novel fusion genes in paediatric high grade glioma |
title_full_unstemmed |
The prognostic role of intragenic copy number breakpoints and identification of novel fusion genes in paediatric high grade glioma |
title_sort |
The prognostic role of intragenic copy number breakpoints and identification of novel fusion genes in paediatric high grade glioma |
author |
Carvalho, Diana |
author_facet |
Carvalho, Diana Mackay, Alan Bjerke, Lynn Grundy, Richard G. Lopes, Celeste Reis, Rui M. Jones, Chris |
author_role |
author |
author2 |
Mackay, Alan Bjerke, Lynn Grundy, Richard G. Lopes, Celeste Reis, Rui M. Jones, Chris |
author2_role |
author author author author author author |
dc.contributor.author.fl_str_mv |
Carvalho, Diana Mackay, Alan Bjerke, Lynn Grundy, Richard G. Lopes, Celeste Reis, Rui M. Jones, Chris |
dc.subject.por.fl_str_mv |
Fusion Paediatric Glioblastoma Copy number Intragenic Algorithms Brain Neoplasms Child Child, Preschool Female Gene Deletion Gene Expression Profiling Glioma Humans Infant Male N-Acetylgalactosaminyltransferases Oligonucleotide Array Sequence Analysis Oncogene Proteins, Fusion RNA, Small Interfering Chromosome Breakage DNA Copy Number Variations |
topic |
Fusion Paediatric Glioblastoma Copy number Intragenic Algorithms Brain Neoplasms Child Child, Preschool Female Gene Deletion Gene Expression Profiling Glioma Humans Infant Male N-Acetylgalactosaminyltransferases Oligonucleotide Array Sequence Analysis Oncogene Proteins, Fusion RNA, Small Interfering Chromosome Breakage DNA Copy Number Variations |
description |
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. |
publishDate |
2014 |
dc.date.none.fl_str_mv |
2014-02-18 |
dc.type.status.fl_str_mv |
info:eu-repo/semantics/publishedVersion |
dc.type.driver.fl_str_mv |
info:eu-repo/semantics/article |
format |
article |
status_str |
publishedVersion |
dc.identifier.uri.fl_str_mv |
http://hdl.handle.net/10316/109353 http://hdl.handle.net/10316/109353 https://doi.org/10.1186/2051-5960-2-23 |
url |
http://hdl.handle.net/10316/109353 https://doi.org/10.1186/2051-5960-2-23 |
dc.language.iso.fl_str_mv |
eng |
language |
eng |
dc.relation.none.fl_str_mv |
2051-5960 |
dc.rights.driver.fl_str_mv |
info:eu-repo/semantics/openAccess |
eu_rights_str_mv |
openAccess |
dc.publisher.none.fl_str_mv |
Springer Nature |
publisher.none.fl_str_mv |
Springer Nature |
dc.source.none.fl_str_mv |
reponame:Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) instname:Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação instacron:RCAAP |
instname_str |
Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação |
instacron_str |
RCAAP |
institution |
RCAAP |
reponame_str |
Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) |
collection |
Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) |
repository.name.fl_str_mv |
Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) - Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação |
repository.mail.fl_str_mv |
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1799134138097205248 |