Format

Send to

Choose Destination
Cell. 2016 Jan 28;164(3):550-63. doi: 10.1016/j.cell.2015.12.028.

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

Collaborators (162)

Anjum S, Arachchi H, Auman JT, Balasundaram M, Balu S, Barnett G, Baylin S, Bell S, Benz C, Bir N, Black KL, Bodenheimer T, Boice L, Bootwalla MS, Bowen J, Bristow CA, Butterfield YS, Chen QR, Chin L, Cho J, Chuah E, Chudamani S, Coetzee SG, Cohen ML, Colman H, Couce M, D'Angelo F, Davidsen T, Davis A, Demchok JA, Devine K, Ding L, Duell R, Elder JB, Eschbacher JM, Fehrenbach A, Ferguson M, Frazer S, Fuller G, Fulop J, Gabriel SB, Garofano L, Gastier-Foster JM, Gehlenborg N, Gerken M, Getz G, Giannini C, Gibson WJ, Hadjipanayis A, Hayes DN, Heiman DI, Hermes B, Hilty J, Hoadley KA, Hoyle AP, Huang M, Jefferys SR, Jones CD, Jones SJ, Ju Z, Kastl A, Kendler A, Kim J, Kucherlapati R, Lai PH, Lawrence MS, Lee S, Leraas KM, Lichtenberg TM, Lin P, Liu Y, Liu J, Ljubimova JY, Lu Y, Ma Y, Maglinte DT, Mahadeshwar HS, Marra MA, McGraw M, McPherson C, Meng S, Mieczkowski PA, Miller CR, Mills GB, Moore RA, Mose LE, Mungall AJ, Naresh R, Naska T, Neder L, Noble MS, Noss A, O'Neill BP, Ostrom QT, Palmer C, Pantazi A, Parfenov M, Park PJ, Parker JS, Perou CM, Pierson CR, Pihl T, Protopopov A, Radenbaugh A, Ramirez NC, Rathmell WK, Ren X, Roach J, Robertson AG, Saksena G, Schein JE, Schumacher SE, Seidman J, Senecal K, Seth S, Shen H, Shi Y, Shih J, Shimmel K, Sicotte H, Sifri S, Silva T, Simons JV, Singh R, Skelly T, Sloan AE, Sofia HJ, Soloway MG, Song X, Sougnez C, Souza C, Staugaitis SM, Sun H, Sun C, Tan D, Tang J, Tang Y, Thorne L, Trevisan FA, Triche T, Van Den Berg DJ, Veluvolu U, Voet D, Wan Y, Wang Z, Warnick R, Weinstein JN, Weisenberger DJ, Wilkerson MD, Williams F, Wise L, Wolinsky Y, Wu J, Xu AW, Yang L, Yang L, Zack TI, Zenklusen JC, Zhang J, Zhang W, Zhang J, Zmuda E.

Author information

1
Qatar Computing Research Institute, Hamad Bin Khalifa University, Doha P.O. box 5825, Qatar; Department of Science and Technology, University of Sannio, Benevento 82100, Italy.
2
Department of Genomic Medicine, Department of Bioinformatics and Computational Biology, Department of Biostatistics, Department of Neuro-Oncology, Department of Neurosurgery, Department of Pathology, University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA; Oncology Graduate School Amsterdam, Department of Pathology, VU University Medical Center, 1081 HV Amsterdam, the Netherlands.
3
Department of Genetics (CISBi/NAP), Department of Surgery and Anatomy, Ribeirão Preto Medical School, University of São Paulo, Monte Alegre, Ribeirão Preto-SP CEP: 14049-900, Brazil; Center for Integrative Systems Biology (CISBi, NAP/USP), Ribeirão Preto Medical School, University of São Paulo, Ribeirão Preto, São Paulo 14049-900, Brazil.
4
UC Santa Cruz Genomics Institute, University of California, Santa Cruz, Santa Cruz, CA 95064, USA.
5
The Eli and Edythe L. Broad Institute of Massachusetts Institute of Technology and Harvard University, Cambridge, MA 02142, USA.
6
Department of Science and Technology, University of Sannio, Benevento 82100, Italy; BIOGEM Istituto di Ricerche Genetiche "G. Salvatore," Campo Reale, 83031 Ariano Irpino, Italy.
7
Qatar Computing Research Institute, Hamad Bin Khalifa University, Doha P.O. box 5825, Qatar.
8
Department of Neurology, Department of Pathology, Institute for Cancer Genetics, Department of Systems Biology and Biomedical Informatics, Columbia University Medical Center, New York, NY 10032, USA.
9
Department of Genomic Medicine, Department of Bioinformatics and Computational Biology, Department of Biostatistics, Department of Neuro-Oncology, Department of Neurosurgery, Department of Pathology, University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
10
Henry Ford Hospital, Detroit, MI 48202, USA.
11
Texas Children's Hospital, Houston, TX 77030, USA; Baylor College of Medicine, Houston, TX 77030, USA.
12
Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA.
13
Winship Cancer Institute, Emory University, Atlanta, GA 30322, USA.
14
Department of Pathology, The Ohio State University, Columbus, OH 43210, USA.
15
Case Comprehensive Cancer Center, Case Western Reserve University, Cleveland, OH 44106, USA.
16
The Eli and Edythe L. Broad Institute of Massachusetts Institute of Technology and Harvard University, Cambridge, MA 02142, USA; Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA 02215, USA.
17
The Eli and Edythe L. Broad Institute of Massachusetts Institute of Technology and Harvard University, Cambridge, MA 02142, USA; Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA 02215, USA; Department of Medicine, Harvard Medical School, Boston, MA 02215, USA.
18
Department of Neurological Surgery, University of California, San Francisco, San Francisco, CA 94158, USA.
19
Princess Margaret Cancer Centre, Toronto, ON M5G 2M9, Canada.
20
Van Andel Research Institute, Grand Rapids, MI 49503, USA.
21
School of Medicine, Washington University, St. Louis, MO 63110, USA.
22
Department of Genetics (CISBi/NAP), Department of Surgery and Anatomy, Ribeirão Preto Medical School, University of São Paulo, Monte Alegre, Ribeirão Preto-SP CEP: 14049-900, Brazil; Center for Integrative Systems Biology (CISBi, NAP/USP), Ribeirão Preto Medical School, University of São Paulo, Ribeirão Preto, São Paulo 14049-900, Brazil. Electronic address: houtan@usp.br.
23
Department of Neurology, Department of Pathology, Institute for Cancer Genetics, Department of Systems Biology and Biomedical Informatics, Columbia University Medical Center, New York, NY 10032, USA. Electronic address: ai2102@columbia.edu.
24
Department of Genomic Medicine, Department of Bioinformatics and Computational Biology, Department of Biostatistics, Department of Neuro-Oncology, Department of Neurosurgery, Department of Pathology, University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA. Electronic address: rverhaak@mdanderson.org.

Abstract

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.

PMID:
26824661
PMCID:
PMC4754110
DOI:
10.1016/j.cell.2015.12.028
[Indexed for MEDLINE]
Free PMC Article

Publication types, MeSH terms, Substances, Grant support

Publication types

MeSH terms

Substances

Grant support

Supplemental Content

Full text links

Icon for Elsevier Science Icon for PubMed Central
Loading ...
Support Center