Integrated proteogenomic characterization across major histological types of pediatric brain cancer Journal Article
| Authors: | Petralia, F.; Tignor, N.; Reva, B.; Koptyra, M.; Chowdhury, S.; Rykunov, D.; Krek, A.; Ma, W.; Zhu, Y.; Ji, J.; Calinawan, A.; Whiteaker, J. R.; Colaprico, A.; Stathias, V.; Omelchenko, T.; Song, X.; Raman, P.; Guo, Y.; Brown, M. A.; Ivey, R. G.; Szpyt, J.; Guha Thakurta, S.; Gritsenko, M. A.; Weitz, K. K.; Lopez, G.; Kalayci, S.; Gümüş, Z. H.; Yoo, S.; da Veiga Leprevost, F.; Chang, H. Y.; Krug, K.; Katsnelson, L.; Wang, Y.; Kennedy, J. J.; Voytovich, U. J.; Zhao, L.; Gaonkar, K. S.; Ennis, B. M.; Zhang, B.; Baubet, V.; Tauhid, L.; Lilly, J. V.; Mason, J. L.; Farrow, B.; Young, N.; Leary, S.; Moon, J.; Petyuk, V. A.; Nazarian, J.; Adappa, N. D.; Palmer, J. N.; Lober, R. M.; Rivero-Hinojosa, S.; Wang, L. B.; Wang, J. M.; Broberg, M.; Chu, R. K.; Moore, R. J.; Monroe, M. E.; Zhao, R.; Smith, R. D.; Zhu, J.; Robles, A. I.; Mesri, M.; Boja, E.; Hiltke, T.; Rodriguez, H.; Zhang, B.; Schadt, E. E.; Mani, D. R.; Ding, L.; Iavarone, A.; Wiznerowicz, M.; Schürer, S.; Chen, X. S.; Heath, A. P.; Rokita, J. L.; Nesvizhskii, A. I.; Fenyö, D.; Rodland, K. D.; Liu, T.; Gygi, S. P.; Paulovich, A. G.; Resnick, A. C.; Storm, P. B.; Rood, B. R.; Wang, P.; Children's Brain Tumor Network; and Clinical Proteomic Tumor Analysis Consortium |
| Article Title: | Integrated proteogenomic characterization across major histological types of pediatric brain cancer |
| Abstract: | We report a comprehensive proteogenomics analysis, including whole-genome sequencing, RNA sequencing, and proteomics and phosphoproteomics profiling, of 218 tumors across 7 histological types of childhood brain cancer: low-grade glioma (n = 93), ependymoma (32), high-grade glioma (25), medulloblastoma (22), ganglioglioma (18), craniopharyngioma (16), and atypical teratoid rhabdoid tumor (12). Proteomics data identify common biological themes that span histological boundaries, suggesting that treatments used for one histological type may be applied effectively to other tumors sharing similar proteomics features. Immune landscape characterization reveals diverse tumor microenvironments across and within diagnoses. Proteomics data further reveal functional effects of somatic mutations and copy number variations (CNVs) not evident in transcriptomics data. Kinase-substrate association and co-expression network analysis identify important biological mechanisms of tumorigenesis. This is the first large-scale proteogenomics analysis across traditional histological boundaries to uncover foundational pediatric brain tumor biology and inform rational treatment selection. © 2020 Elsevier Inc. Integrative proteogenomics analysis of pediatric tumors identifies common underlying biological processes and potential treatments as well as the functional effects of somatic mutations and CNVs driving tumorigenesis. © 2020 Elsevier Inc. |
| Keywords: | tumor microenvironment; pediatric brain tumor; post-translational modification; cptac; braf alteration; ctnnb1 mutation; kinase activity score; kinase substrate regulation; proteomic cluster; recurrent versus primary tumors |
| Journal Title: | Cell |
| Volume: | 183 |
| Issue: | 7 |
| ISSN: | 0092-8674 |
| Publisher: | Cell Press |
| Date Published: | 2020-12-23 |
| Start Page: | 1962 |
| End Page: | 1985.e31 |
| Language: | English |
| DOI: | 10.1016/j.cell.2020.10.044 |
| PUBMED: | 33242424 |
| PROVIDER: | scopus |
| PMCID: | PMC8143193 |
| DOI/URL: | |
| Notes: | Article -- Export Date: 4 January 2021 -- Source: Scopus |
