@article{fe132201d3cf420faa1a73d8f4c75a56,
title = "Multi-scale signaling and tumor evolution in high-grade gliomas",
abstract = "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.",
keywords = "CPTAC, glioblastoma, glycoproteomics, lipidome, metabolome, proteomics, single nuclei ATAC-seq, single nuclei RNA-seq, tumor recurrence",
author = "{Philadelphia Coalition for a Cure} and {Clinical Proteomic Tumor Analysis Consortium} and Jingxian Liu and Song Cao and Imbach, {Kathleen J.} and Gritsenko, {Marina A.} and Lih, {Tung Shing M.} and Kyle, {Jennifer E.} and Yaron-Barir, {Tomer M.} and Binder, {Zev A.} and Yize Li and Ilya Strunilin and Wang, {Yi Ting} and Tsai, {Chia Feng} and Weiping Ma and Lijun Chen and Clark, {Natalie M.} and Andrew Shinkle and {Naser Al Deen}, Nataly and Wagma Caravan and Andrew Houston and Simin, {Faria Anjum} and Wyczalkowski, {Matthew A.} and Wang, {Liang Bo} and Erik Storrs and Siqi Chen and Ritvik Illindala and Li, {Yuping D.} and Jayasinghe, {Reyka G.} and Dmitry Rykunov and Cottingham, {Sandra L.} and Chu, {Rosalie K.} and Weitz, {Karl K.} and Moore, {Ronald J.} and Tyler Sagendorf and Petyuk, {Vladislav A.} and Michael Nestor and Bramer, {Lisa M.} and Stratton, {Kelly G.} and Schepmoes, {Athena A.} and Couvillion, {Sneha P.} and Josie Eder and Kim, {Young Mo} and Yuqian Gao and Fillmore, {Thomas L.} and Rui Zhao and Monroe, {Matthew E.} and Southard-Smith, {Austin N.} and Li, {Yang E.} and {Jui-Hsien Lu}, Rita and Johnson, {Jared L.} and Maciej Wiznerowicz and Galen Hostetter and Newton, {Chelsea J.} and Ketchum, {Karen A.} and Thangudu, {Ratna R.} and Barnholtz-Sloan, {Jill S.} and Pei Wang and David Feny{\"o} and Eunkyung An and Mathangi Thiagarajan and Robles, {Ana I.} and Mani, {D. R.} and Smith, {Richard D.} and Eduard Porta-Pardo and Cantley, {Lewis C.} and Antonio Iavarone and Feng Chen and Mehdi Mesri and Nasrallah, {MacLean P.} and Hui Zhang and Resnick, {Adam C.} and Chheda, {Milan G.} and Rodland, {Karin D.} and Tao Liu and Li Ding",
note = "Publisher Copyright: {\textcopyright} 2024 The Authors",
year = "2024",
month = jul,
day = "8",
doi = "10.1016/j.ccell.2024.06.004",
language = "English",
volume = "42",
pages = "1217--1238.e19",
journal = "Cancer Cell",
issn = "1535-6108",
number = "7",
}