Proteogenomic and metabolomic characterization of human glioblastoma.
Brain Neoplasms
/ metabolism
Computational Biology
/ methods
Glioblastoma
/ genetics
Humans
Metabolomics
/ methods
Mutation
/ genetics
Phospholipase C gamma
/ genetics
Phosphorylation
/ physiology
Protein Tyrosine Phosphatase, Non-Receptor Type 11
/ genetics
Proteogenomics
/ methods
Proteomics
/ methods
CPTAC
acetylome
glioblastoma
lipidome
metabolome
proteogenomics
proteomics
signaling
single nuclei RNA-seq
Journal
Cancer cell
ISSN: 1878-3686
Titre abrégé: Cancer Cell
Pays: United States
ID NLM: 101130617
Informations de publication
Date de publication:
12 04 2021
12 04 2021
Historique:
received:
03
02
2020
revised:
02
06
2020
accepted:
11
01
2021
pubmed:
13
2
2021
medline:
17
11
2021
entrez:
12
2
2021
Statut:
ppublish
Résumé
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.
Identifiants
pubmed: 33577785
pii: S1535-6108(21)00050-7
doi: 10.1016/j.ccell.2021.01.006
pmc: PMC8044053
mid: NIHMS1665743
pii:
doi:
Substances chimiques
PTPN11 protein, human
EC 3.1.3.48
Protein Tyrosine Phosphatase, Non-Receptor Type 11
EC 3.1.3.48
PLCG1 protein, human
EC 3.1.4.11
Phospholipase C gamma
EC 3.1.4.3
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Langues
eng
Sous-ensembles de citation
IM
Pagination
509-528.e20Subventions
Organisme : NCI NIH HHS
ID : U24 CA210954
Pays : United States
Organisme : NCI NIH HHS
ID : U24 CA210985
Pays : United States
Organisme : NCI NIH HHS
ID : U24 CA210967
Pays : United States
Organisme : NCI NIH HHS
ID : U24 CA210986
Pays : United States
Organisme : NCI NIH HHS
ID : U24 CA210972
Pays : United States
Organisme : NCI NIH HHS
ID : U24 CA210955
Pays : United States
Organisme : NINDS NIH HHS
ID : K08 NS102474
Pays : United States
Organisme : NCI NIH HHS
ID : U24 CA210979
Pays : United States
Organisme : NCI NIH HHS
ID : U01 CA214125
Pays : United States
Organisme : NHGRI NIH HHS
ID : R01 HG009711
Pays : United States
Organisme : NCI NIH HHS
ID : U24 CA160019
Pays : United States
Organisme : NINDS NIH HHS
ID : R01 NS107833
Pays : United States
Organisme : NCI NIH HHS
ID : U24 CA210993
Pays : United States
Investigateurs
Anupriya Agarwal
(A)
Mitual Amin
(M)
Eunkyung An
(E)
Matthew L Anderson
(ML)
David W Andrews
(DW)
Thomas Bauer
(T)
Chet Birger
(C)
Michael J Birrer
(MJ)
Lili Blumenberg
(L)
William E Bocik
(WE)
Uma Borate
(U)
Melissa Borucki
(M)
Meghan C Burke
(MC)
Shuang Cai
(S)
Anna P Calinawan
(AP)
Steven A Carr
(SA)
Sandra Cerda
(S)
Daniel W Chan
(DW)
Alyssa Charamut
(A)
Lin S Chen
(LS)
David Chesla
(D)
Arul M Chinnaiyan
(AM)
Shrabanti Chowdhury
(S)
Marcin P Cieślik
(MP)
David J Clark
(DJ)
Houston Culpepper
(H)
Tomasz Czernicki
(T)
Fulvio D'Angelo
(F)
Jacob Day
(J)
Stephanie De Young
(S)
Emek Demir
(E)
Saravana Mohan Dhanasekaran
(SM)
Rajiv Dhir
(R)
Marcin J Domagalski
(MJ)
Brian Druker
(B)
Elizabeth Duffy
(E)
Maureen Dyer
(M)
Nathan J Edwards
(NJ)
Robert Edwards
(R)
Kimberly Elburn
(K)
Matthew J Ellis
(MJ)
Jennifer Eschbacher
(J)
Alicia Francis
(A)
Stacey Gabriel
(S)
Nikolay Gabrovski
(N)
Luciano Garofano
(L)
Gad Getz
(G)
Michael A Gillette
(MA)
Andrew K Godwin
(AK)
Denis Golbin
(D)
Ziad Hanhan
(Z)
Linda I Hannick
(LI)
Pushpa Hariharan
(P)
Barbara Hindenach
(B)
Katherine A Hoadley
(KA)
Galen Hostetter
(G)
Chen Huang
(C)
Eric Jaehnig
(E)
Scott D Jewell
(SD)
Nan Ji
(N)
Corbin D Jones
(CD)
Alcida Karz
(A)
Wojciech Kaspera
(W)
Lyndon Kim
(L)
Ramani B Kothadia
(RB)
Chandan Kumar-Sinha
(C)
Jonathan Lei
(J)
Felipe D Leprevost
(FD)
Kai Li
(K)
Yuxing Liao
(Y)
Jena Lilly
(J)
Hongwei Liu
(H)
Jan Lubínski
(J)
Rashna Madan
(R)
William Maggio
(W)
Ewa Malc
(E)
Anna Malovannaya
(A)
Sailaja Mareedu
(S)
Sanford P Markey
(SP)
Annette Marrero-Oliveras
(A)
Nina Martinez
(N)
Nicollette Maunganidze
(N)
Jason E McDermott
(JE)
Peter B McGarvey
(PB)
John McGee
(J)
Piotr Mieczkowski
(P)
Simona Migliozzi
(S)
Francesmary Modugno
(F)
Rebecca Montgomery
(R)
Chelsea J Newton
(CJ)
Gilbert S Omenn
(GS)
Umut Ozbek
(U)
Oxana V Paklina
(OV)
Amanda G Paulovich
(AG)
Amy M Perou
(AM)
Alexander R Pico
(AR)
Paul D Piehowski
(PD)
Dimitris G Placantonakis
(DG)
Larisa Polonskaya
(L)
Olga Potapova
(O)
Barbara Pruetz
(B)
Liqun Qi
(L)
Shakti Ramkissoon
(S)
Adam Resnick
(A)
Shannon Richey
(S)
Gregory Riggins
(G)
Karna Robinson
(K)
Nancy Roche
(N)
Daniel C Rohrer
(DC)
Brian R Rood
(BR)
Larissa Rossell
(L)
Sara R Savage
(SR)
Eric E Schadt
(EE)
Yan Shi
(Y)
Zhiao Shi
(Z)
Yvonne Shutack
(Y)
Shilpi Singh
(S)
Tara Skelly
(T)
Lori J Sokoll
(LJ)
Jakub Stawicki
(J)
Stephen E Stein
(SE)
James Suh
(J)
Wojciech Szopa
(W)
Dave Tabor
(D)
Donghui Tan
(D)
Darlene Tansil
(D)
Ratna R Thangudu
(RR)
Cristina Tognon
(C)
Elie Traer
(E)
Shirley Tsang
(S)
Jeffrey Tyner
(J)
Ki Sung Um
(KS)
Dana R Valley
(DR)
Suhas Vasaikar
(S)
Negin Vatanian
(N)
Uma Velvulou
(U)
Michael Vernon
(M)
Weiqing Wan
(W)
Junmei Wang
(J)
Alex Webster
(A)
Bo Wen
(B)
Jeffrey R Whiteaker
(JR)
George D Wilson
(GD)
Yuriy Zakhartsev
(Y)
Robert Zelt
(R)
Hui Zhang
(H)
Liwei Zhang
(L)
Zhen Zhang
(Z)
Grace Zhao
(G)
Jun Zhu
(J)
Informations de copyright
Copyright © 2021 The Authors. Published by Elsevier Inc. All rights reserved.
Déclaration de conflit d'intérêts
Declaration of interests S.Y. is employed by Sema4. A.H.K. consults for Monteris Medical. P.W. is a statistical consultant for Sema4. M.G.C. receives research support from Orbus Therapeutics and NeoimmuneTech Inc, and royalties from UpToDate.
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