Integrated molecular meta-analysis of 1,000 pediatric high-grade and diffuse intrinsic pontine glioma

Detalhes bibliográficos
Autor(a) principal: Mackay, Alan
Data de Publicação: 2017
Outros Autores: Burford, Anna, Carvalho, Diana, Izquierdo, Elisa, Fazal-Salom, Janat, Taylor, Kathryn R., Bjerke, Lynn, Clarke, Matthew, Vinci, Mara, Reis, R. M.
Tipo de documento: Artigo
Idioma: eng
Título da fonte: Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)
Texto Completo: http://hdl.handle.net/1822/48958
Resumo: We collated data from 157 unpublished cases of pediatric high-grade glioma and diffuse intrinsic pontine glioma and 20 publicly available datasets in an integrated analysis of > 1,000 cases. We identified co-segregating mutations in histone-mutant subgroups including loss of FBXW7 in H3.3G34R/V, TOP3A rearrangements in H3.3K27M, and BCOR mutations in H3.1K27M. Histone wild-type subgroups are refined by the presence of key oncogenic events or methylation profiles more closely resembling lower-grade tumors. Genomic aberrations increase with age, highlighting the infant population as biologically and clinically distinct. Uncommon pathway dysregulation is seen in small subsets of tumors, further defining the molecular diversity of the disease, opening up avenues for biological study and providing a basis for functionally defined future treatment stratification.
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spelling Integrated molecular meta-analysis of 1,000 pediatric high-grade and diffuse intrinsic pontine gliomaDIPGexomegenomeglioblastomahistonemethylationScience & TechnologyWe collated data from 157 unpublished cases of pediatric high-grade glioma and diffuse intrinsic pontine glioma and 20 publicly available datasets in an integrated analysis of > 1,000 cases. We identified co-segregating mutations in histone-mutant subgroups including loss of FBXW7 in H3.3G34R/V, TOP3A rearrangements in H3.3K27M, and BCOR mutations in H3.1K27M. Histone wild-type subgroups are refined by the presence of key oncogenic events or methylation profiles more closely resembling lower-grade tumors. Genomic aberrations increase with age, highlighting the infant population as biologically and clinically distinct. Uncommon pathway dysregulation is seen in small subsets of tumors, further defining the molecular diversity of the disease, opening up avenues for biological study and providing a basis for functionally defined future treatment stratification.This work was supported by Cancer Research UK (grants C13468/A13982 and C13468/A23536), CRIS Cancer Foundation, Abbie’s Army and the DIPG Collaborative, the Cure Starts Now Foundation, Christopher’s Smile, McKenna Claire Foundation, Lyla Nsouli Foundation, National Institutes of Health (grants R01NS085336 and R01NS091620), The Dragon Master Foundation, The Kortney Rose Foundation, The Musella Foundation For Brain Tumor Research & Information, Gray Matters Foundation, Pediatric Brain Tumor Foundation, and the INSTINCT network funded by The Brain Tumour Charity, Great Ormond Street Children’s Charity, and Children with Cancer UK. The authors acknowledge NHS funding to the NIHR Biomedical Research Centre at The Royal Marsden and the ICR. LTB was recipient of Sa˜ o Paulo Research Foundation fellowships (2011/08523-7 and 2012/08287-4). This study makes use of data generated by the St. Jude Children’s Research Hospital – Washington University Pediatric Cancer Genome Project, the Hospital for Sick Children, the McGill University-DKFZ Pediatric Brain Tumor Consortium, the International Cancer Genomics Consortium PedBrain Project and the Cancer Research UK Genomics Initiative (C13468/A14078) and supports the Children’s Brain Tumor Tissue Consortium and The Pacific Pediatric Neuro-Oncology Consortium (PNOC) CAVATICA: Project OPEN DIPG initiative.info:eu-repo/semantics/publishedVersionElsevier[et. al.]Universidade do MinhoMackay, AlanBurford, AnnaCarvalho, DianaIzquierdo, ElisaFazal-Salom, JanatTaylor, Kathryn R.Bjerke, LynnClarke, MatthewVinci, MaraReis, R. M.2017-09-282017-09-28T00:00:00Zinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articleapplication/pdfhttp://hdl.handle.net/1822/48958eng1535-61081878-368610.1016/j.ccell.2017.08.01728966033http://www.cell.com/cancer-cell/comments/S1535-6108info: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:RCAAP2023-07-21T12:39:33Zoai:repositorium.sdum.uminho.pt:1822/48958Portal AgregadorONGhttps://www.rcaap.pt/oai/openaireopendoar:71602024-03-19T19:36:11.313071Repositório 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 Integrated molecular meta-analysis of 1,000 pediatric high-grade and diffuse intrinsic pontine glioma
title Integrated molecular meta-analysis of 1,000 pediatric high-grade and diffuse intrinsic pontine glioma
spellingShingle Integrated molecular meta-analysis of 1,000 pediatric high-grade and diffuse intrinsic pontine glioma
Mackay, Alan
DIPG
exome
genome
glioblastoma
histone
methylation
Science & Technology
title_short Integrated molecular meta-analysis of 1,000 pediatric high-grade and diffuse intrinsic pontine glioma
title_full Integrated molecular meta-analysis of 1,000 pediatric high-grade and diffuse intrinsic pontine glioma
title_fullStr Integrated molecular meta-analysis of 1,000 pediatric high-grade and diffuse intrinsic pontine glioma
title_full_unstemmed Integrated molecular meta-analysis of 1,000 pediatric high-grade and diffuse intrinsic pontine glioma
title_sort Integrated molecular meta-analysis of 1,000 pediatric high-grade and diffuse intrinsic pontine glioma
author Mackay, Alan
author_facet Mackay, Alan
Burford, Anna
Carvalho, Diana
Izquierdo, Elisa
Fazal-Salom, Janat
Taylor, Kathryn R.
Bjerke, Lynn
Clarke, Matthew
Vinci, Mara
Reis, R. M.
author_role author
author2 Burford, Anna
Carvalho, Diana
Izquierdo, Elisa
Fazal-Salom, Janat
Taylor, Kathryn R.
Bjerke, Lynn
Clarke, Matthew
Vinci, Mara
Reis, R. M.
author2_role author
author
author
author
author
author
author
author
author
dc.contributor.none.fl_str_mv [et. al.]
Universidade do Minho
dc.contributor.author.fl_str_mv Mackay, Alan
Burford, Anna
Carvalho, Diana
Izquierdo, Elisa
Fazal-Salom, Janat
Taylor, Kathryn R.
Bjerke, Lynn
Clarke, Matthew
Vinci, Mara
Reis, R. M.
dc.subject.por.fl_str_mv DIPG
exome
genome
glioblastoma
histone
methylation
Science & Technology
topic DIPG
exome
genome
glioblastoma
histone
methylation
Science & Technology
description We collated data from 157 unpublished cases of pediatric high-grade glioma and diffuse intrinsic pontine glioma and 20 publicly available datasets in an integrated analysis of > 1,000 cases. We identified co-segregating mutations in histone-mutant subgroups including loss of FBXW7 in H3.3G34R/V, TOP3A rearrangements in H3.3K27M, and BCOR mutations in H3.1K27M. Histone wild-type subgroups are refined by the presence of key oncogenic events or methylation profiles more closely resembling lower-grade tumors. Genomic aberrations increase with age, highlighting the infant population as biologically and clinically distinct. Uncommon pathway dysregulation is seen in small subsets of tumors, further defining the molecular diversity of the disease, opening up avenues for biological study and providing a basis for functionally defined future treatment stratification.
publishDate 2017
dc.date.none.fl_str_mv 2017-09-28
2017-09-28T00:00:00Z
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/1822/48958
url http://hdl.handle.net/1822/48958
dc.language.iso.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv 1535-6108
1878-3686
10.1016/j.ccell.2017.08.017
28966033
http://www.cell.com/cancer-cell/comments/S1535-6108
dc.rights.driver.fl_str_mv info:eu-repo/semantics/openAccess
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv application/pdf
dc.publisher.none.fl_str_mv Elsevier
publisher.none.fl_str_mv Elsevier
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
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