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Structural variants shape driver combinations and outcomes in pediatric high-grade glioma.
Dubois, Frank P B; Shapira, Ofer; Greenwald, Noah F; Zack, Travis; Wala, Jeremiah; Tsai, Jessica W; Crane, Alexander; Baguette, Audrey; Hadjadj, Djihad; Harutyunyan, Ashot S; Kumar, Kiran H; Blattner-Johnson, Mirjam; Vogelzang, Jayne; Sousa, Cecilia; Kang, Kyung Shin; Sinai, Claire; Wang, Dayle K; Khadka, Prasidda; Lewis, Kathleen; Nguyen, Lan; Malkin, Hayley; Ho, Patricia; O'Rourke, Ryan; Zhang, Shu; Gold, Rose; Deng, Davy; Serrano, Jonathan; Snuderl, Matija; Jones, Chris; Wright, Karen D; Chi, Susan N; Grill, Jacques; Kleinman, Claudia L; Goumnerova, Liliana C; Jabado, Nada; Jones, David T W; Kieran, Mark W; Ligon, Keith L; Beroukhim, Rameen; Bandopadhayay, Pratiti.
Afiliação
  • Dubois FPB; Department of Cancer Biology, Dana-Farber Cancer Institute and Harvard Medical School, Boston, MA, USA.
  • Shapira O; Broad Institute of MIT and Harvard, Cambridge, MA, USA.
  • Greenwald NF; Department of Cancer Biology, Dana-Farber Cancer Institute and Harvard Medical School, Boston, MA, USA.
  • Zack T; Broad Institute of MIT and Harvard, Cambridge, MA, USA.
  • Wala J; Department of Cancer Biology, Dana-Farber Cancer Institute and Harvard Medical School, Boston, MA, USA.
  • Tsai JW; Broad Institute of MIT and Harvard, Cambridge, MA, USA.
  • Crane A; Department of Cancer Biology, Dana-Farber Cancer Institute and Harvard Medical School, Boston, MA, USA.
  • Baguette A; Broad Institute of MIT and Harvard, Cambridge, MA, USA.
  • Hadjadj D; Department of Cancer Biology, Dana-Farber Cancer Institute and Harvard Medical School, Boston, MA, USA.
  • Harutyunyan AS; Broad Institute of MIT and Harvard, Cambridge, MA, USA.
  • Kumar KH; Broad Institute of MIT and Harvard, Cambridge, MA, USA.
  • Blattner-Johnson M; Department of Pediatrics, Harvard Medical School, Boston, MA, USA.
  • Vogelzang J; Department of Pediatric Oncology, Dana-Farber Boston Children's Cancer and Blood Disorders Center, Boston, MA, USA.
  • Sousa C; Department of Cancer Biology, Dana-Farber Cancer Institute and Harvard Medical School, Boston, MA, USA.
  • Kang KS; Broad Institute of MIT and Harvard, Cambridge, MA, USA.
  • Sinai C; Quantitative Life Sciences, McGill University, Montreal, QC, Canada.
  • Wang DK; Department of Human Genetics, McGill University, Montreal, QC, Canada.
  • Khadka P; Department of Human Genetics, McGill University, Montreal, QC, Canada.
  • Lewis K; Department of Cancer Biology, Dana-Farber Cancer Institute and Harvard Medical School, Boston, MA, USA.
  • Nguyen L; Broad Institute of MIT and Harvard, Cambridge, MA, USA.
  • Malkin H; Hopp Children's Cancer Center Heidelberg (KiTZ), Heidelberg, Germany.
  • Ho P; Division of Pediatric Glioma Research, German Cancer Consortium (DKTK), German Cancer Research Center (DKFZ), Heidelberg, Germany.
  • O'Rourke R; Department of Pathology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA, USA.
  • Zhang S; Department of Pathology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA, USA.
  • Gold R; Department of Cancer Biology, Dana-Farber Cancer Institute and Harvard Medical School, Boston, MA, USA.
  • Deng D; Broad Institute of MIT and Harvard, Cambridge, MA, USA.
  • Serrano J; Department of Pathology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA, USA.
  • Snuderl M; Broad Institute of MIT and Harvard, Cambridge, MA, USA.
  • Jones C; Department of Pediatric Oncology, Dana-Farber Boston Children's Cancer and Blood Disorders Center, Boston, MA, USA.
  • Wright KD; Department of Cancer Biology, Dana-Farber Cancer Institute and Harvard Medical School, Boston, MA, USA.
  • Chi SN; Broad Institute of MIT and Harvard, Cambridge, MA, USA.
  • Grill J; Broad Institute of MIT and Harvard, Cambridge, MA, USA.
  • Kleinman CL; Broad Institute of MIT and Harvard, Cambridge, MA, USA.
  • Goumnerova LC; Department of Pathology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA, USA.
  • Jabado N; Department of Cancer Biology, Dana-Farber Cancer Institute and Harvard Medical School, Boston, MA, USA.
  • Jones DTW; Broad Institute of MIT and Harvard, Cambridge, MA, USA.
  • Kieran MW; Department of Cancer Biology, Dana-Farber Cancer Institute and Harvard Medical School, Boston, MA, USA.
  • Ligon KL; Broad Institute of MIT and Harvard, Cambridge, MA, USA.
  • Beroukhim R; Department of Cancer Biology, Dana-Farber Cancer Institute and Harvard Medical School, Boston, MA, USA.
  • Bandopadhayay P; Broad Institute of MIT and Harvard, Cambridge, MA, USA.
Nat Cancer ; 3(8): 994-1011, 2022 08.
Article em En | MEDLINE | ID: mdl-35788723
ABSTRACT
We analyzed the contributions of structural variants (SVs) to gliomagenesis across 179 pediatric high-grade gliomas (pHGGs). The most recurrent SVs targeted MYC isoforms and receptor tyrosine kinases (RTKs), including an SV amplifying a MYC enhancer in 12% of diffuse midline gliomas (DMG), indicating an underappreciated role for MYC in pHGG. SV signature analysis revealed that tumors with simple signatures were TP53 wild type (TP53WT) but showed alterations in TP53 pathway members PPM1D and MDM4. Complex signatures were associated with direct aberrations in TP53, CDKN2A and RB1 early in tumor evolution and with later-occurring extrachromosomal amplicons. All pHGGs exhibited at least one simple-SV signature, but complex-SV signatures were primarily restricted to subsets of H3.3K27M DMGs and hemispheric pHGGs. Importantly, DMGs with complex-SV signatures were associated with shorter overall survival independent of histone mutation and TP53 status. These data provide insight into the impact of SVs on gliomagenesis and the mechanisms that shape them.
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Texto completo: 1 Base de dados: MEDLINE Assunto principal: Neoplasias Encefálicas / Glioma Idioma: En Ano de publicação: 2022 Tipo de documento: Article País de afiliação: Estados Unidos
Texto completo
Imprimir
XML
PubMed Links
Buscar no Google

Texto completo: 1 Base de dados: MEDLINE Assunto principal: Neoplasias Encefálicas / Glioma Idioma: En Ano de publicação: 2022 Tipo de documento: Article País de afiliação: Estados Unidos