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Molecular Profiling Reveals Biologically Discrete Subsets and Pathways of Progression in Diffuse Glioma

Therapy development for adult diffuse glioma is hindered by incomplete knowledge of somatic glioma driving alterations and suboptimal disease classification. We defined the complete set of genes associated with 1,122 diffuse grade II-III-IV gliomas from The Cancer Genome Atlas and used molecular pro... Full description

Journal Title: Cell 28 January 2016, Vol.164(3), pp.550-563
Main Author: Ceccarelli, Michele
Other Authors: Barthel, Floris p , Malta, Tathiane m , Sabedot, Thais s , Salama, Sofie r , Murray, Bradley a , Morozova, Olena , Newton, Yulia , Radenbaugh, Amie , Pagnotta, Stefano m , Anjum, Samreen , Wang, Jiguang , Manyam, Ganiraju , Zoppoli, Pietro
Format: Electronic Article Electronic Article
Language: English
Subjects:
ID: ISSN: 0092-8674 ; E-ISSN: 1097-4172 ; DOI: 10.1016/j.cell.2015.12.028
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recordid: elsevier_sdoi_10_1016_j_cell_2015_12_028
title: Molecular Profiling Reveals Biologically Discrete Subsets and Pathways of Progression in Diffuse Glioma
format: Article
creator:
  • Ceccarelli, Michele
  • Barthel, Floris p
  • Malta, Tathiane m
  • Sabedot, Thais s
  • Salama, Sofie r
  • Murray, Bradley a
  • Morozova, Olena
  • Newton, Yulia
  • Radenbaugh, Amie
  • Pagnotta, Stefano m
  • Anjum, Samreen
  • Wang, Jiguang
  • Manyam, Ganiraju
  • Zoppoli, Pietro
subjects:
  • Biology
ispartof: Cell, 28 January 2016, Vol.164(3), pp.550-563
description: Therapy development for adult diffuse glioma is hindered by incomplete knowledge of somatic glioma driving alterations and suboptimal disease classification. We defined the complete set of genes associated with 1,122 diffuse grade II-III-IV gliomas from The Cancer Genome Atlas and used molecular profiles to improve disease classification, identify molecular correlations, and provide insights into the progression from low- to high-grade disease. Whole-genome sequencing data analysis determined that ATRX but not TERT promoter mutations are associated with increased telomere length. Recent advances in glioma classification based on IDH mutation and 1p/19q co-deletion status were recapitulated through analysis of DNA methylation profiles, which identified clinically relevant molecular subsets. A subtype of IDH mutant glioma was associated with DNA demethylation and poor outcome; a group of IDH-wild-type diffuse glioma showed molecular similarity to pilocytic astrocytoma and relatively...
language: eng
source:
identifier: ISSN: 0092-8674 ; E-ISSN: 1097-4172 ; DOI: 10.1016/j.cell.2015.12.028
fulltext: fulltext
issn:
  • 0092-8674
  • 00928674
  • 1097-4172
  • 10974172
url: Link


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titleMolecular Profiling Reveals Biologically Discrete Subsets and Pathways of Progression in Diffuse Glioma
creatorCeccarelli, Michele ; Barthel, Floris p ; Malta, Tathiane m ; Sabedot, Thais s ; Salama, Sofie r ; Murray, Bradley a ; Morozova, Olena ; Newton, Yulia ; Radenbaugh, Amie ; Pagnotta, Stefano m ; Anjum, Samreen ; Wang, Jiguang ; Manyam, Ganiraju ; Zoppoli, Pietro
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descriptionTherapy development for adult diffuse glioma is hindered by incomplete knowledge of somatic glioma driving alterations and suboptimal disease classification. We defined the complete set of genes associated with 1,122 diffuse grade II-III-IV gliomas from The Cancer Genome Atlas and used molecular profiles to improve disease classification, identify molecular correlations, and provide insights into the progression from low- to high-grade disease. Whole-genome sequencing data analysis determined that ATRX but not TERT promoter mutations are associated with increased telomere length. Recent advances in glioma classification based on IDH mutation and 1p/19q co-deletion status were recapitulated through analysis of DNA methylation profiles, which identified clinically relevant molecular subsets. A subtype of IDH mutant glioma was associated with DNA demethylation and poor outcome; a group of IDH-wild-type diffuse glioma showed molecular similarity to pilocytic astrocytoma and relatively...
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titleMolecular Profiling Reveals Biologically Discrete Subsets and Pathways of Progression in Diffuse Glioma
description

Therapy development for adult diffuse glioma is hindered by incomplete knowledge of somatic glioma driving alterations and suboptimal disease classification. We defined the complete set of genes associated with 1,122 diffuse grade II-III-IV gliomas from The Cancer Genome Atlas and used molecular profiles to improve disease classification, identify molecular correlations, and provide insights into the progression from low- to high-grade disease. Whole-genome sequencing data analysis determined that ATRX but not TERT promoter mutations are associated with increased telomere length. Recent advances in glioma classification based on IDH mutation and 1p/19q co-deletion status were recapitulated through analysis of DNA methylation profiles, which identified clinically relevant molecular subsets. A subtype of IDH mutant glioma was associated with DNA demethylation and poor outcome; a group of IDH-wild-type diffuse glioma showed molecular similarity to pilocytic astrocytoma and relatively...

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Therapy development for adult diffuse glioma is hindered by incomplete knowledge of somatic glioma driving alterations and suboptimal disease classification. We defined the complete set of genes associated with 1,122 diffuse grade II-III-IV gliomas from The Cancer Genome Atlas and used molecular profiles to improve disease classification, identify molecular correlations, and provide insights into the progression from low- to high-grade disease. Whole-genome sequencing data analysis determined that ATRX but not TERT promoter mutations are associated with increased telomere length. Recent advances in glioma classification based on IDH mutation and 1p/19q co-deletion status were recapitulated through analysis of DNA methylation profiles, which identified clinically relevant molecular subsets. A subtype of IDH mutant glioma was associated with DNA demethylation and poor outcome; a group of IDH-wild-type diffuse glioma showed molecular similarity to pilocytic astrocytoma and relatively...

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