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Proteogenomic and metabolomic characterization of human glioblastoma

  1. Author:
    Wang, Liang-Bo
    Karpova, Alla
    Gritsenko, Marina A.
    Kyle, Jennifer E.
    Cao, Song
    Li, Yize
    Rykunov, Dmitry
    Colaprico, Antonio
    Rothstein, Joseph H.
    Hong, Runyu
    Stathias, Vasileios
    Cornwell, MacIntosh
    Petralia, Francesca
    Wu, Yige
    Reva, Boris
    Krug, Karsten
    Pugliese, Pietro
    Kawaler, Emily
    Olsen, Lindsey K.
    Liang, Wen-Wei
    Song, Xiaoyu
    Dou, Yongchao
    Wendl, Michael C.
    Caravan, Wagma
    Liu, Wenke
    Zhou, Daniel Cui
    Ji, Jiayi
    Tsai, Chia-Feng
    Petyuk, Vladislav A.
    Moon, Jamie
    Ma, Weiping
    Chu, Rosalie K.
    Weitz, Karl K.
    Moore, Ronald J.
    Monroe, Matthew E.
    Zhao, Rui
    Yang, Xiaolu
    Yoo, Seungyeul
    Krek, Azra
    Demopoulos, Alexis
    Zhu, Houxiang
    Wyczalkowski, Matthew A.
    McMichael, Joshua F.
    Henderson, Brittany L.
    Lindgren, Caleb M.
    Boekweg, Hannah
    Lu, Shuangjia
    Baral, Jessika
    Yao, Lijun
    Stratton, Kelly G.
    Bramer, Lisa M.
    Zink, Erika
    Couvillion, Sneha P.
    Bloodsworth, Kent J.
    Satpathy, Shankha
    Sieh, Weiva
    Boca, Simina M.
    Schurer, Stephan
    Chen, Feng
    Wiznerowicz, Maciej
    Ketchum, Karen A.
    Boja, Emily S.
    Kinsinger, Christopher R.
    Robles, Ana
    Hiltke, Tara
    Thiagarajan,Mathangi
    Nesvizhskii, Alexey
    Zhang, Bing
    Mani, D. R.
    Ceccarelli, Michele
    Chen, Xi S.
    Cottingham, Sandra L.
    Li, Qing Kay
    Kim, Albert H.
    Fenyo, David
    Ruggles, Kelly
    Rodriguez, Henry
    Mesri, Mehdi
    Payne, Samuel H.
    Resnick, Adam C.
    Wang, Pei
    Smith, Richard D.
    Iavarone, Antonio
    Chheda, Milan G.
    Barnholtz-Sloan, Jill S.
    Rodland, Karin D.
    Liu, Tao
    Ding, Li

  2. Author Address

    Washington Univ, Dept Med, St Louis, MO 63130 USA.Washington Univ, McDonnell Genome Inst, Richland, WA 63130 USA.Pacific Northwest Natl Lab, Biol Sci Div, Richland, WA 99354 USA.Icahn Sch Med Mt Sinai, Icahn Inst Genom & Multiscale Biol, Dept Genet & Genom Sci, New York, NY 10029 USA.Univ Miami, Dept Publ Hlth Sci, Sylvester Comprehens Canc Ctr, Miami, FL 33136 USA.Univ Miami, Dept Publ Hlth Sci, Div Biostat, Miami, FL 33136 USA.NYU, Inst Syst Genet, Grossman Sch Med, New York, NY 10016 USA.NYU, Dept Biochem & Mol Pharmacol, Grossman Sch Med, New York, NY 10016 USA.Univ Miami, Miller Sch Med, Dept Mol & Cellular Pharmacol, Miami, FL 33136 USA.BD2K LINCS Data Coordinat & Integrat Ctr, Miami, FL 33136 USA.NYU, Dept Med, Grossman Sch Med, New York, NY 10016 USA.Broad Inst MIT & Harvard, Cambridge, MA 02142 USA.Univ Sannio, Dept Sci & Technol, I-82100 Benevento, Italy.Brigham Young Univ, Dept Biol, Provo, UT 84602 USA.Icahn Sch Med Mt Sinai, Tisch Canc Inst, New York, NY 10029 USA.Icahn Sch Med Mt Sinai, Dept Populat Hlth Sci & Policy, New York, NY 10029 USA.Baylor Coll Med, Lester & Sue Smith Breast Ctr, Houston, TX 77030 USA.Baylor Coll Med, Dept Mol & Human Genet, Houston, TX 77030 USA.Washington Univ, Dept Genet, St Louis, MO 63130 USA.Washington Univ, Dept Math, St Louis, MO 63130 USA.Northwell Hlth Syst, Dept Neurol, Lake Success, NY 11042 USA.Georgetown Univ, Innovat Ctr Biomed Informat, Med Ctr, Washington, DC 20007 USA.Univ Miami, Inst Data Sci & Comp, Miami, FL 33136 USA.Washington Univ, Dept Cell Biol & Physiol, St Louis, MO 63130 USA.Washington Univ, Siteman Canc Ctr, St Louis, MO 63130 USA.Int Inst Mol Oncol, PL-60203 Poznan, Poland.Poznan Univ Med Sci, PL-61701 Poznan, Poland.ESAC Inc, Rockville, MD 20850 USA.NCI, Off Canc Clin Prote Res, Bethesda, MD 20892 USA.Frederick Natl Lab Canc Res, Frederick, MD 21702 USA.Univ Michigan, Dept Pathol, Ann Arbor, MI 48109 USA.Univ Michigan, Dept Computat Med & Bioinformat, Ann Arbor, MI 48109 USA.Univ Naples Federico II, Dept Elect Engn & Informat Technol, I-80128 Naples, Italy.Spectrum Hlth & Helen DeVos Childrens Hosp, Dept Pathol, Grand Rapids, MI 49503 USA.Johns Hopkins Univ, Dept Pathol, Baltimore, MD 21231 USA.Washington Univ, Dept Neurol Surg, St Louis, MO 63130 USA.Childrens Hosp Philadelphia, Ctr Data Driven Discovery Biomed, Philadelphia, PA 19104 USA.Childrens Hosp Philadelphia, Div Neurosurg, Philadelphia, PA 19104 USA.Columbia Univ Med Ctr, Inst Canc Genet, New York, NY 10032 USA.Columbia Univ, Dept Neurol, Med Ctr, New York, NY 10032 USA.Columbia Univ, Dept Pathol & Cell Biol, Med Ctr, New York, NY 10032 USA.Columbia Univ, Herbert Irving Comprehens Canc Ctr, Med Ctr, New York, NY 10032 USA.Washington Univ, Dept Neurol, St Louis, MO 63130 USA.Case Western Reserve Univ, Case Comprehens Canc Ctr, Sch Med, Cleveland, OH 44106 USA.Case Western Reserve Univ, Dept Populat & Quantitat Hlth Sci, Sch Med, Cleveland, OH 44106 USA.Univ Hosp Hlth Syst, Res & Educ, Cleveland, OH 44106 USA.Oregon Hlth & Sci Univ, Dept Cell Dev & Canc Biol, Portland, OR 97221 USA.BIOGEM, I-83031 Ariano Irpino, Italy.
    1. Year: 2021
    2. Date: Apr 12
  2. Journal: Cancer Cell
  3. CELL PRESS,
    1. 39
    2. 4
    3. Pages: 509-528.e20
  5. Type of Article: Article
  6. ISSN: 1535-6108
  1. Abstract:

    Glioblastoma (GBM) is the most aggressive nervous system cancer. Understanding its molecular pathogenesis is crucial to improving diagnosis and treatment. Integrated analysis of genomic, proteomic, post-translational modification and metabolomic data on 99 treatment-naive GBMs provides insights to GBM biology. We identify key phosphorylation events (e.g., phosphorylated PTPN11 and PLCG1) as potential switches mediating oncogenic pathway activation, as well as potential targets for EGFR-, TP53-, and RB1-altered tumors. Immune subtypes with distinct immune cell types are discovered using bulk omics methodologies, validated by snRNA-seq, and correlated with specific expression and histone acetylation patterns. Histone H2B acetylation in classical-like and immune-low GBM is driven largely by BRDs, CREBBP, and EP300. Integrated metabolomic and proteomic data identify specific lipid distributions across subtypes and distinct global metabolic changes in IDH-mutated tumors. This work highlights biological relationships that could contribute to stratification of GBM patients for more effective treatment.

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External Sources

  1. View Full Text
  2. DOI: 10.1016/j.ccell.2021.01.006
  3. PMID: 33577785
  4. PMCID: PMC8044053
  5. View record in Web of Science®
  6. WOS: 000640027300012

Library Notes

  1. Fiscal Year: FY2020-2021
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