Multi-scale signaling and tumor evolution in high-grade gliomas

• DOI: 10.1016/j.ccell.2024.06.004
• Publication Date: 2024-07-08T14:50:20Z
• Authors: Jingxian Liu; Song Cao; Kathleen J. Imbach; Marina A. Gritsenko; Tung-Shing M. Lih; Jennifer E. Kyle; Tomer M. Yaron-Barir; Zev A. Binder; Yize Li; Ilya Strunilin; Yi-Ting Wang; Chia-Feng Tsai; Weiping Ma; Lijun Chen; Natalie M. Clark; Andrew Shinkle; Nataly Naser Al Deen; Wagma Caravan; Andrew Houston; Faria Anjum Simin; Matthew A. Wyczal...; Liang-Bo Wang; Erik Storrs; Siqi Chen; Ritvik Illindala; Yuping D. Li; Reyka G. Jayasinghe; Dmitry Rykunov; Sandra L. Cottingham; Rosalie K. Chu; Karl K. Weitz; Ronald J. Moore; Tyler Sagendorf; Vladislav A. Petyuk; Michael Nestor; Lisa M. Bramer; Kelly G. Stratton; Athena A. Schepmoes; Sneha P. Couvillion; Josie Eder; Young-Mo Kim; Yuqian Gao; Thomas L. Fillmore; Rui Zhao; Matthew E. Monroe; Austin N. Southar...; Yang E. Li; Rita Jui-Hsien Lu; Jared L. Johnson; Maciej Wiznerowicz; Galen Hostetter; Chelsea J. Newton; Karen A. Ketchum; Ratna R. Thangudu; Jill S. Barnholtz...; Pei Wang; David Fenyö; Eunkyung An; Mathangi Thiagarajan; Ana I. Robles; D.R. Mani; Richard D. Smith; Eduard Porta-Pardo; Lewis C. Cantley; Antonio Iavarone; Feng Chen; Mehdi Mesri; MacLean P. Nasrallah; Hui Zhang; Adam C. Resnick; Milan G. Chheda; Karin D. Rodland; Tao Liu; Li Ding; Anupriya Agarwal; Iyad Alnahhas; Mitual Amin; Eunkyung An; Matthew L. Anderson; David W. Andrews; Meenakshi Anurag; Jill S. Barnholtz...; Thomas Bauer; Jasmin Bavarva; Zev A. Binder; Michael J. Birrer; Uma Borate; Melissa Borucki; Lisa M. Bramer; Steven Brem; Shuang Cai; Lewis C. Cantley; Song Cao; Wagma Caravan; Steven A Carr; Daniel W. Chan; Lijun Chen; Lin S. Chen; Xi S. Chen; David Chesla; Milan G. Chheda; Arul M. Chinnaiyan; Shrabanti Chowdhury; Rosalie K. Chu; Marcin P. Cieślik; Natalie M. Clark; Karl Clauser; Antonio Colaprico; Sandra L. Cottingham; Sneha P. Couvillion; Reese Crispen; Tomasz Czernicki; Fulvio D’Angelo; Emek Demir; Saravana Mohan Dh...; Li Ding; Marcin J. Domagalski; Yongchao Dou; Brian Druker; Josie Eder; Nathan J. Edwards; Jennifer Eschbacher; David Fenyő; Thomas H. Fillmore; Nikolay Gabrovski; Yuqian Gao; Luciano Garofano; Yifat Geffen; Gad Getz; Michael A. Gillette; Denis Golbin; Charles A. Goldth...; Marina A. Gritsenko; Zeynep Gumus; Ziad Hanhan; Beth Hermes; Tara Hiltke; Galen Hostetter; Andrew Houston; Chen Huang; Antonio Iavarone; Kathleen J. Imbach; Eric Jaehnig; Scott D. Jewell; Jared L. Johnson; Kevin D. Judy; Alicia Karz; Wojciech Kaspera; Karen A. Ketchum; Lyndon Kim; Young-Mo Kim; Mateusz P Koptyra; Ramani B Kothadia; Chandan Kumar-Sinha; Jennifer E. Kyle; John Y.K. Lee; Jonathan Lei; Felipe D. Leprevost; Kai Li; Qing Kay Li; Yize Li; Zibo Li; Yuxing Liao; Tung-Shing M. Lih; Jena Lilly; Jingxian Liu; Tao Liu; Rita Jui-Hsien Lu; Yin Lu; Jan Lubínski; Weiping Ma; William Maggio; Anna Malovannaya; D.R. Mani; Nina Martinez; Jason E. McDermott; Peter B. McGarvey; Mehdi Mesri; Simona Migliozzi; Matthew E. Monroe; Ronald J. Moore; Nataly Naser Al Deen; MacLean P. Nasrallah; Michael Nestor; Alexey I. Nesvizh...; Chelsea J. Newton; Donald M. O’Rourke; Gilbert S. Omenn; Umut Ozbek; Oxana V. Paklina; Amanda G. Paulovich; Samuel H. Payne; Francesca Petralia; Vladislav A. Petyuk; Alexander R. Pico; Paul D. Piehowski; Alexander Pilozzi; Dmitris Placanton...; Eduard Porta-Pardo; Olga Potapova; Barbara Pruetz; Adam C. Resnick; Boris Reva; Ana I. Robles; Karin D. Rodland; Henry Rodriguez; Daniel C. Rohrer; Brian Rood; Larissa Rossell; Kelly V. Ruggles; Dmitry Rykunov; Tyler Sagendorf; Atom Sarkar; Shankha Satpathy; Sara R. Savage; Eric E. Schadt; Athena A. Schepmoes; Scott R. Shepard; Zhiao Shi; Yvonne Shutack; Richard D. Smith; Lori J. Sokoll; Yingduo Song; Yizhe Song; Austin N. Southar...; Jakub Stawicki; Phillip B. Storm; Kelly G. Stratton; Ilya Strunilin; Wojciech Szopa; Ratna R. Thangudu; Mathangi Thiagarajan; Cristina Tognon; Elie Traer; Chia-Feng Tsai; Shirley Tsang; Alan R. Turtz; Jeffrey Tyner; Negin Vatanian; Weiqing Wan; Liang-Bo Wang; Pei Wang; Yi-Ting Wang; Michael W. Weaver; Karl K. Weitz; Bo Wen; Jeffrey R. Whiteaker; Bart Williams; George D. Wilson; Maciej Wiznerowicz; Yige Wu; Matthew A. Wyczal...; Lijun Yao; Tomer M. Yaron; Eric L. Zager; Bing Zhang; Hui Zhang; Xu Zhang; Zhen Zhang; Rui Zhao; Jun Zhu
• Keywords: Proteome

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 IDH-wildtype GBM and IDH-mutant grade 4 astrocytoma, by integrating proteomic, metabolomic, lipidomic, post-translational modifications (PTMs) with transcriptomic measurements uncover multi-scale regulatory interactions governing tumor development evolution. Applying 14 proteogenomic metabolomic platforms 228 tumors (212 16 astrocytoma), including 28 at recurrence, plus 18 normal brain samples metastases as comparators, reveals heterogeneous upstream alterations converging on common downstream events proteomic levels changes protein-protein glycosylation site occupancy recurrence. Recurrent genetic phosphorylation PTPN11 map important domains three dimensions, suggesting central role signaling across gliomas.