| Literature DB >> 33577785 |
Liang-Bo Wang1, Alla Karpova1, Marina A Gritsenko2, Jennifer E Kyle2, Song Cao1, Yize Li1, Dmitry Rykunov3, Antonio Colaprico4, Joseph H Rothstein3, Runyu Hong5, Vasileios Stathias6, MacIntosh Cornwell7, Francesca Petralia3, Yige Wu1, Boris Reva3, Karsten Krug8, Pietro Pugliese9, Emily Kawaler5, Lindsey K Olsen10, Wen-Wei Liang1, Xiaoyu Song11, Yongchao Dou12, Michael C Wendl13, Wagma Caravan1, Wenke Liu5, Daniel Cui Zhou1, Jiayi Ji11, Chia-Feng Tsai2, Vladislav A Petyuk2, Jamie Moon2, Weiping Ma3, Rosalie K Chu2, Karl K Weitz2, Ronald J Moore2, Matthew E Monroe2, Rui Zhao2, Xiaolu Yang14, Seungyeul Yoo3, Azra Krek3, Alexis Demopoulos15, Houxiang Zhu1, Matthew A Wyczalkowski1, Joshua F McMichael1, Brittany L Henderson10, Caleb M Lindgren10, Hannah Boekweg10, Shuangjia Lu1, Jessika Baral1, Lijun Yao1, Kelly G Stratton2, Lisa M Bramer2, Erika Zink2, Sneha P Couvillion2, Kent J Bloodsworth2, Shankha Satpathy8, Weiva Sieh16, Simina M Boca17, Stephan Schürer18, Feng Chen19, Maciej Wiznerowicz20, Karen A Ketchum21, Emily S Boja22, Christopher R Kinsinger22, Ana I Robles22, Tara Hiltke22, Mathangi Thiagarajan23, Alexey I Nesvizhskii24, Bing Zhang12, D R Mani8, Michele Ceccarelli25, Xi S Chen4, Sandra L Cottingham26, Qing Kay Li27, Albert H Kim28, David Fenyö5, Kelly V Ruggles7, Henry Rodriguez22, Mehdi Mesri22, Samuel H Payne10, Adam C Resnick29, Pei Wang3, Richard D Smith2, Antonio Iavarone30, Milan G Chheda31, Jill S Barnholtz-Sloan32, Karin D Rodland33, Tao Liu34, Li Ding35.
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.Entities:
Keywords: CPTAC; acetylome; glioblastoma; lipidome; metabolome; proteogenomics; proteomics; signaling; single nuclei RNA-seq
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Year: 2021 PMID： 33577785 PMCID： PMC8044053 DOI： 10.1016/j.ccell.2021.01.006
Source DB: PubMed Journal: Cancer Cell ISSN： 1535-6108 Impact factor: 31.743