TY - JOUR
T1 - Proteogenomic and metabolomic characterization of human glioblastoma
AU - Clinical Proteomic Tumor Analysis Consortium
AU - Wang, Liang Bo
AU - Karpova, Alla
AU - Gritsenko, Marina A.
AU - Kyle, Jennifer E.
AU - Cao, Song
AU - Li, Yize
AU - Rykunov, Dmitry
AU - Colaprico, Antonio
AU - Rothstein, Joseph H.
AU - Hong, Runyu
AU - Stathias, Vasileios
AU - Cornwell, MacIntosh
AU - Petralia, Francesca
AU - Wu, Yige
AU - Reva, Boris
AU - Krug, Karsten
AU - Pugliese, Pietro
AU - Kawaler, Emily
AU - Olsen, Lindsey K.
AU - Liang, Wen Wei
AU - Song, Xiaoyu
AU - Dou, Yongchao
AU - Wendl, Michael C.
AU - Caravan, Wagma
AU - Liu, Wenke
AU - Cui Zhou, Daniel
AU - Ji, Jiayi
AU - Tsai, Chia Feng
AU - Petyuk, Vladislav A.
AU - Moon, Jamie
AU - Ma, Weiping
AU - Chu, Rosalie K.
AU - Weitz, Karl K.
AU - Moore, Ronald J.
AU - Monroe, Matthew E.
AU - Zhao, Rui
AU - Yang, Xiaolu
AU - Yoo, Seungyeul
AU - Krek, Azra
AU - Demopoulos, Alexis
AU - Zhu, Houxiang
AU - Wyczalkowski, Matthew A.
AU - McMichael, Joshua F.
AU - Henderson, Brittany L.
AU - Lindgren, Caleb M.
AU - Sieh, Weiva
AU - Wang, Pei
AU - Chowdhury, Shrabanti
AU - Kim, Lyndon
AU - Ozbek, Umut
N1 - Publisher Copyright:
© 2021 The Authors
PY - 2021/4/12
Y1 - 2021/4/12
N2 - 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.
AB - 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.
KW - CPTAC
KW - acetylome
KW - glioblastoma
KW - lipidome
KW - metabolome
KW - proteogenomics
KW - proteomics
KW - signaling
KW - single nuclei RNA-seq
UR - http://www.scopus.com/inward/record.url?scp=85101666510&partnerID=8YFLogxK
U2 - 10.1016/j.ccell.2021.01.006
DO - 10.1016/j.ccell.2021.01.006
M3 - Article
C2 - 33577785
AN - SCOPUS:85101666510
SN - 1535-6108
VL - 39
SP - 509-528.e20
JO - Cancer Cell
JF - Cancer Cell
IS - 4
ER -