Cancer cell · 2024

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

СтатьяПоддержка NIH: внешняя программаПоддержка исследования: вне правительства СШАНазвание и аннотация: Перевод пока не подготовлен

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Liu Jingxian, Cao Song, Imbach Kathleen J, Gritsenko Marina A, Lih Tung-Shing M, Kyle Jennifer E, Yaron-Barir Tomer M, Binder Zev A, Li Yize, Strunilin Ilya, Wang Yi-Ting, Tsai Chia-Feng, Ma Weiping, Chen Lijun, Clark Natalie M, Shinkle Andrew, Naser Al Deen Nataly, Caravan Wagma, Houston Andrew, Simin Faria Anjum, Wyczalkowski Matthew A, Wang Liang-Bo, Storrs Erik, Chen Siqi, Illindala Ritvik, Li Yuping D, Jayasinghe Reyka G, Rykunov Dmitry, Cottingham Sandra L, Chu Rosalie K, Weitz Karl K, Moore Ronald J, Sagendorf Tyler, Petyuk Vladislav A, Nestor Michael, Bramer Lisa M, Stratton Kelly G, Schepmoes Athena A, Couvillion Sneha P, Eder Josie, Kim Young-Mo, Gao Yuqian, Fillmore Thomas L, Zhao Rui, Monroe Matthew E, Southard-Smith Austin N, Li Yang E, Jui-Hsien Lu Rita, Johnson Jared L, Wiznerowicz Maciej, Hostetter Galen, Newton Chelsea J, Ketchum Karen A, Thangudu Ratna R, Barnholtz-Sloan Jill S, Wang Pei, Fenyö David, An Eunkyung, Thiagarajan Mathangi, Robles Ana I, Mani D R, Smith Richard D, Porta-Pardo Eduard, Cantley Lewis C, Iavarone Antonio, Chen Feng, Mesri Mehdi, Nasrallah MacLean P, Zhang Hui, Resnick Adam C, Chheda Milan G, Rodland Karin D, Liu Tao, Ding Li, Philadelphia Coalition for a Cure, Clinical Proteomic Tumor Analysis Consortium

Аннотация

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.

Предметные рубрики MeSH

Humans Brain Neoplasms Signal Transduction Protein Tyrosine Phosphatase, Non-Receptor Type 11 Glioma Mutation Proteomics Protein Processing, Post-Translational Gene Expression Regulation, Neoplastic Glioblastoma Phosphorylation Neoplasm Grading Isocitrate Dehydrogenase

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

Ошибки и ограничения

Аннотация

Предметные рубрики MeSH