%0 Journal Article
%T Multi-scale signaling and tumor evolution in high-grade gliomas.
%A Liu J
%A Cao S
%A Imbach KJ
%A Gritsenko MA
%A Lih TM
%A Kyle JE
%A Yaron-Barir TM
%A Binder ZA
%A Li Y
%A Strunilin I
%A Wang YT
%A Tsai CF
%A Ma W
%A Chen L
%A Clark NM
%A Shinkle A
%A Naser Al Deen N
%A Caravan W
%A Houston A
%A Simin FA
%A Wyczalkowski MA
%A Wang LB
%A Storrs E
%A Chen S
%A Illindala R
%A Li YD
%A Jayasinghe RG
%A Rykunov D
%A Cottingham SL
%A Chu RK
%A Weitz KK
%A Moore RJ
%A Sagendorf T
%A Petyuk VA
%A Nestor M
%A Bramer LM
%A Stratton KG
%A Schepmoes AA
%A Couvillion SP
%A Eder J
%A Kim YM
%A Gao Y
%A Fillmore TL
%A Zhao R
%A Monroe ME
%A Southard-Smith AN
%A Li YE
%A Jui-Hsien Lu R
%A Johnson JL
%A Wiznerowicz M
%A Hostetter G
%A Newton CJ
%A Ketchum KA
%A Thangudu RR
%A Barnholtz-Sloan JS
%A Wang P
%A Fenyö D
%A An E
%A Thiagarajan M
%A Robles AI
%A Mani DR
%A Smith RD
%A Porta-Pardo E
%A Cantley LC
%A Iavarone A
%A Chen F
%A Mesri M
%A Nasrallah MP
%A Zhang H
%A Resnick AC
%A Chheda MG
%A Rodland KD
%A Liu T
%A Ding L
%A  
%A  
%J Cancer Cell
%V 42
%N 7
%D 2024 Jul 8
%M 38981438
%F 38.585
%R 10.1016/j.ccell.2024.06.004
%X Although genomic anomalies in glioblastoma (GBM) have been well studied for over a decade, its 5-year survival rate remains lower than 5%. We seek to expand the molecular landscape of high-grade glioma, composed of IDH-wildtype GBM and IDH-mutant grade 4 astrocytoma, by integrating proteomic, metabolomic, lipidomic, and post-translational modifications (PTMs) with genomic and transcriptomic measurements to uncover multi-scale regulatory interactions governing tumor development and evolution. Applying 14 proteogenomic and metabolomic platforms to 228 tumors (212 GBM and 16 grade 4 IDH-mutant astrocytoma), including 28 at recurrence, plus 18 normal brain samples and 14 brain metastases as comparators, reveals heterogeneous upstream alterations converging on common downstream events at the proteomic and metabolomic levels and changes in protein-protein interactions and glycosylation site occupancy at recurrence. Recurrent genetic alterations and phosphorylation events on PTPN11 map to important regulatory domains in three dimensions, suggesting a central role for PTPN11 signaling across high-grade gliomas.