Molecular profiling reveals biologically discrete subsets and pathways of progression in diffuse glioma Journal Article


Authors: Ceccarelli, M.; Barthel, F. P.; Malta, T. M.; Sabedot, T. S.; Salama, S. R.; Murray, B. A.; Morozova, O.; Newton, Y.; Radenbaugh, A.; Pagnotta, S. M.; Anjum, S.; Wang, J.; Manyam, G.; Zoppoli, P.; Ling, S.; Rao, A. A.; Grifford, M.; Cherniack, A. D.; Zhang, H.; Poisson, L.; Carlotti, C. G. Jr; Tirapelli, D. P. D. C.; Rao, A.; Mikkelsen, T.; Lau, C. C.; Yung, W. K. A.; Rabadan, R.; Huse, J.; Brat, D. J.; Lehman, N. L.; Barnholtz-Sloan, J. S.; Zheng, S.; Hess, K.; Rao, G.; Meyerson, M.; Beroukhim, R.; Cooper, L.; Akbani, R.; Wrensch, M.; Haussler, D.; Aldape, K. D.; Laird, P. W.; Gutmann, D. H.; TCGA Research Network; Noushmehr, H.; Iavarone, A.; Verhaak, R. G. W.
Article Title: Molecular profiling reveals biologically discrete subsets and pathways of progression in diffuse glioma
Abstract: Summary 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 favorable survival. Understanding of cohesive disease groups may aid improved clinical outcomes. © 2016 Elsevier Inc.
Keywords: protein expression; gene mutation; promoter region; somatic mutation; mutation; glioma; cancer grading; genetic analysis; telomere; gene expression; genetic transcription; mutational analysis; dna methylation; dna; messenger rna; epigenetics; quantitative analysis; telomerase reverse transcriptase; gene control; dna sequence; gene dosage; tumor growth; molecular biology; tumor classification; protein microarray; genetic selection; rna sequence; rna analysis; indel mutation; data processing; human; priority journal; article
Journal Title: Cell
Volume: 164
Issue: 3
ISSN: 0092-8674
Publisher: Cell Press  
Date Published: 2016-01-28
Start Page: 550
End Page: 563
Language: English
DOI: 10.1016/j.cell.2015.12.028
PROVIDER: scopus
PMCID: PMC4754110
PUBMED: 26824661
DOI/URL:
Notes: Article -- Export Date: 3 March 2016 -- Source: Scopus
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  1. Jason T Huse
    132 Huse