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Molecular Profiling Reveals Biologically Discrete Subsets and Pathways of Progression in Diffuse Glioma.
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; Ling, Shiyun; Rao, Arjun A; Grifford, Mia; Cherniack, Andrew D; Zhang, Hailei; Poisson, Laila; Carlotti, Carlos Gilberto; Tirapelli, Daniela Pretti da Cunha; Rao, Arvind; Mikkelsen, Tom; Lau, Ching C; Yung, W K Alfred; Rabadan, Raul; Huse, Jason; Brat, Daniel J; Lehman, Norman L; Barnholtz-Sloan, Jill S; Zheng, Siyuan; Hess, Kenneth; Rao, Ganesh; Meyerson, Matthew; Beroukhim, Rameen; Cooper, Lee; Akbani, Rehan; Wrensch, Margaret; Haussler, David; Aldape, Kenneth D; Laird, Peter W; Gutmann, David H; Noushmehr, Houtan; Iavarone, Antonio; Verhaak, Roel G W.
Affiliation
  • Ceccarelli M; 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.
  • Barthel FP; 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 Amst
  • Malta TM; 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, Ribe
  • Sabedot TS; 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, Ribe
  • Salama SR; UC Santa Cruz Genomics Institute, University of California, Santa Cruz, Santa Cruz, CA 95064, USA.
  • Murray BA; The Eli and Edythe L. Broad Institute of Massachusetts Institute of Technology and Harvard University, Cambridge, MA 02142, USA.
  • Morozova O; UC Santa Cruz Genomics Institute, University of California, Santa Cruz, Santa Cruz, CA 95064, USA.
  • Newton Y; UC Santa Cruz Genomics Institute, University of California, Santa Cruz, Santa Cruz, CA 95064, USA.
  • Radenbaugh A; UC Santa Cruz Genomics Institute, University of California, Santa Cruz, Santa Cruz, CA 95064, USA.
  • Pagnotta SM; Department of Science and Technology, University of Sannio, Benevento 82100, Italy; BIOGEM Istituto di Ricerche Genetiche "G. Salvatore," Campo Reale, 83031 Ariano Irpino, Italy.
  • Anjum S; Qatar Computing Research Institute, Hamad Bin Khalifa University, Doha P.O. box 5825, Qatar.
  • Wang J; 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.
  • Manyam G; 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.
  • Zoppoli P; 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.
  • Ling S; 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.
  • Rao AA; UC Santa Cruz Genomics Institute, University of California, Santa Cruz, Santa Cruz, CA 95064, USA.
  • Grifford M; UC Santa Cruz Genomics Institute, University of California, Santa Cruz, Santa Cruz, CA 95064, USA.
  • Cherniack AD; The Eli and Edythe L. Broad Institute of Massachusetts Institute of Technology and Harvard University, Cambridge, MA 02142, USA.
  • Zhang H; The Eli and Edythe L. Broad Institute of Massachusetts Institute of Technology and Harvard University, Cambridge, MA 02142, USA.
  • Poisson L; Henry Ford Hospital, Detroit, MI 48202, USA.
  • Carlotti CG; 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, Ribe
  • Tirapelli DP; 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, Ribe
  • Rao A; 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.
  • Mikkelsen T; Henry Ford Hospital, Detroit, MI 48202, USA.
  • Lau CC; Texas Children's Hospital, Houston, TX 77030, USA; Baylor College of Medicine, Houston, TX 77030, USA.
  • Yung WK; 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.
  • Rabadan R; 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.
  • Huse J; Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA.
  • Brat DJ; Winship Cancer Institute, Emory University, Atlanta, GA 30322, USA.
  • Lehman NL; Department of Pathology, The Ohio State University, Columbus, OH 43210, USA.
  • Barnholtz-Sloan JS; Case Comprehensive Cancer Center, Case Western Reserve University, Cleveland, OH 44106, USA.
  • Zheng S; 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.
  • Hess K; 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.
  • Rao G; 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.
  • Meyerson M; 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.
  • Beroukhim R; 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.
  • Cooper L; Winship Cancer Institute, Emory University, Atlanta, GA 30322, USA.
  • Akbani R; 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.
  • Wrensch M; Department of Neurological Surgery, University of California, San Francisco, San Francisco, CA 94158, USA.
  • Haussler D; UC Santa Cruz Genomics Institute, University of California, Santa Cruz, Santa Cruz, CA 95064, USA.
  • Aldape KD; Princess Margaret Cancer Centre, Toronto, ON M5G 2M9, Canada.
  • Laird PW; Van Andel Research Institute, Grand Rapids, MI 49503, USA.
  • Gutmann DH; School of Medicine, Washington University, St. Louis, MO 63110, USA.
  • Noushmehr H; 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, Ribe
  • Iavarone A; 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.
  • Verhaak RG; 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@
Cell ; 164(3): 550-63, 2016 Jan 28.
Article in En | MEDLINE | ID: mdl-26824661
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.
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Full text: 1 Database: MEDLINE Main subject: Brain Neoplasms / Transcriptome / Glioma Limits: Adult / Humans / Middle aged Language: En Journal: Cell Year: 2016 Type: Article Affiliation country: Italy
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Full text: 1 Database: MEDLINE Main subject: Brain Neoplasms / Transcriptome / Glioma Limits: Adult / Humans / Middle aged Language: En Journal: Cell Year: 2016 Type: Article Affiliation country: Italy