1. Beijing Key Laboratory of Gene Resource and Molecular Development, Laboratory of Neuroscience and Brain Development, Beijing Normal University, Beijing 100875, China 2. Beijing Neurosurgical Institute, Beijing 100070, China 3. Department of Neurosurgery, Beijing Tiantan Hospital, Capital Medical University, Beijing 100070, China 4. Department of Pathology, Affiliated Hospital of Hebei University, Baoding 071000, China 5. Gendya Biotechnology Ltd., Beijing 100176, China 6. Center of Growth Metabolism & Aging, Key Laboratory of Bio-Resource and Eco-Environment of Ministry of Education, College of Life Sciences, Sichuan University, Chengdu 610065, China 7. Department of Pathology, Sanbo Brain Hospital, Capital Medical University, Beijing 100093, China 8. Biodynamic Optical Imaging Center (BIOPIC), School of Life Sciences, Peking University, Beijing 100871, China 9. Department of Neurosurgery, Affiliated Hospital of Hebei University, Baoding 071000, China; Hebei Key Laboratory of Precise Diagnosis and Treatment of Glioma, Baoding 071000, China 10. Chinese Glioma Genome Atlas Network (CGGA), Beijing 100070, China
Detailed characterizations of genomic alterations have not identified subtype-specific vulnerabilities in adult gliomas. Mapping gliomas into developmental programs may uncover new vulnerabilities that are not strictly related to genomic alterations. After identifying conserved gene modules co-expressed with EGFR or PDGFRA (EM or PM), we recently proposed an EM/PM classification scheme for adult gliomas in a histological subtype- and grade-independent manner. By using cohorts of bulk samples, paired primary and recurrent samples, multi-region samples from the same glioma, single-cell RNA-seq samples, and clinical samples, we here demonstrate the temporal and spatial stability of the EM and PM subtypes. The EM and PM subtypes, which progress in a subtype-specific mode, are robustly maintained in paired longitudinal samples. Elevated activities of cell proliferation, genomic instability and microenvironment, rather than subtype switching, mark recurrent gliomas. Within individual gliomas, the EM/PM subtype was preserved across regions and single cells. Malignant cells in the EM and PM gliomas were correlated to neural stem cell and oligodendrocyte progenitor cell compartment, respectively. Thus, while genetic makeup may change during progression and/or within different tumor areas, adult gliomas evolve within a neurodevelopmental framework of the EM and PM molecular subtypes. The dysregulated developmental pathways embedded in these molecular subtypes may contain subtype-specific vulnerabilities.
K Aldape, KM Brindle, L Chesler, R Chopra, A Gajjar, MR Gilbert, N Gottardo, DH Gutmann, D Hargrave, EC Holland, DTW Jones, JA Joyce, P Kearns, MW Kieran, IK Mellinghoff, M Merchant, SM Pfister, SM Pollard, V Ramaswamy, JN Rich, GW Robinson, DH Rowitch, JH Sampson, MD Taylor, P Workman, RJ Gilbertson. Challenges to curing primary brain tumours. Nat Rev Clin Oncol 2019; 16(8): 509–520 https://doi.org/10.1038/s41571-019-0177-5
pmid: 30733593
2
M Touat, A Idbaih, M Sanson, KL Ligon. Glioblastoma targeted therapy: updated approaches from recent biological insights. Ann Oncol 2017; 28(7): 1457–1472 https://doi.org/10.1093/annonc/mdx106
pmid: 28863449
3
LA Garraway, WR Sellers. Lineage dependency and lineage-survival oncogenes in human cancer. Nat Rev Cancer 2006; 6(8): 593–602 https://doi.org/10.1038/nrc1947
pmid: 16862190
4
P Westervelt, TJ Ley. Seed versus soil: the importance of the target cell for transgenic models of human leukemias. Blood 1999; 93(7): 2143–2148 https://doi.org/10.1182/blood.V93.7.2143
pmid: 10090920
5
SR Alcantara Llaguno, LF Parada. Cell of origin of glioma: biological and clinical implications. Br J Cancer 2016; 115(12): 1445–1450 https://doi.org/10.1038/bjc.2016.354
pmid: 27832665
6
DN Louis, A Perry, G Reifenberger, A von Deimling, D Figarella-Branger, WK Cavenee, H Ohgaki, OD Wiestler, P Kleihues, DW Ellison. The 2016 World Health Organization Classification of Tumors of the Central Nervous System: a summary. Acta Neuropathol 2016; 131(6): 803–820 https://doi.org/10.1007/s00401-016-1545-1
pmid: 27157931
7
A Sottoriva, I Spiteri, SG Piccirillo, A Touloumis, VP Collins, JC Marioni, C Curtis, C Watts, S Tavaré. Intratumor heterogeneity in human glioblastoma reflects cancer evolutionary dynamics. Proc Natl Acad Sci USA 2013; 110(10): 4009–4014 https://doi.org/10.1073/pnas.1219747110
pmid: 23412337
8
M Weller, den Bent M van, M Preusser, Rhun E Le, JC Tonn, G Minniti, M Bendszus, C Balana, O Chinot, L Dirven, P French, ME Hegi, AS Jakola, M Platten, P Roth, R Rudà, S Short, M Smits, MJB Taphoorn, Deimling A von, M Westphal, R Soffietti, G Reifenberger, W Wick. EANO guidelines on the diagnosis and treatment of diffuse gliomas of adulthood. Nat Rev Clin Oncol 2021; 18(3): 170–186 https://doi.org/10.1038/s41571-020-00447-z
pmid: 33293629
9
DN Louis, A Perry, P Wesseling, DJ Brat, IA Cree, D Figarella-Branger, C Hawkins, HK Ng, SM Pfister, G Reifenberger, R Soffietti, A von Deimling, DW Ellison. The 2021 WHO Classification of Tumors of the Central Nervous System: a summary. Neuro-oncol 2021; 23(8): 1231–1251 https://doi.org/10.1093/neuonc/noab106
pmid: 34185076
10
M Cieślik, AM Chinnaiyan. Cancer transcriptome profiling at the juncture of clinical translation. Nat Rev Genet 2018; 19(2): 93–109 https://doi.org/10.1038/nrg.2017.96
pmid: 29279605
11
RG Verhaak, KA Hoadley, E Purdom, V Wang, Y Qi, MD Wilkerson, CR Miller, L Ding, T Golub, JP Mesirov, G Alexe, M Lawrence, M O’Kelly, P Tamayo, BA Weir, S Gabriel, W Winckler, S Gupta, L Jakkula, HS Feiler, JG Hodgson, CD James, JN Sarkaria, C Brennan, A Kahn, PT Spellman, RK Wilson, TP Speed, JW Gray, M Meyerson, G Getz, CM Perou, DN; Cancer Genome Atlas Research Network Hayes. Integrated genomic analysis identifies clinically relevant subtypes of glioblastoma characterized by abnormalities in PDGFRA, IDH1, EGFR, and NF1. Cancer Cell 2010; 17(1): 98–110 https://doi.org/10.1016/j.ccr.2009.12.020
pmid: 20129251
12
Q Wang, B Hu, X Hu, H Kim, M Squatrito, L Scarpace, AC deCarvalho, S Lyu, P Li, Y Li, F Barthel, HJ Cho, YH Lin, N Satani, E Martinez-Ledesma, S Zheng, E Chang, CG Sauvé, A Olar, ZD Lan, G Finocchiaro, JJ Phillips, MS Berger, KR Gabrusiewicz, G Wang, E Eskilsson, J Hu, T Mikkelsen, RA DePinho, F Muller, AB Heimberger, EP Sulman, DH Nam, RGW Verhaak. Tumor evolution of glioma-intrinsic gene expression subtypes associates with immunological changes in the microenvironment. Cancer Cell 2017; 32(1): 42–56.e6 https://doi.org/10.1016/j.ccell.2017.06.003
pmid: 28697342
13
J Wang, E Cazzato, E Ladewig, V Frattini, DI Rosenbloom, S Zairis, F Abate, Z Liu, O Elliott, YJ Shin, JK Lee, IH Lee, WY Park, M Eoli, AJ Blumberg, A Lasorella, DH Nam, G Finocchiaro, A Iavarone, R Rabadan. Clonal evolution of glioblastoma under therapy. Nat Genet 2016; 48(7): 768–776 https://doi.org/10.1038/ng.3590
pmid: 27270107
14
AP Patel, I Tirosh, JJ Trombetta, AK Shalek, SM Gillespie, H Wakimoto, DP Cahill, BV Nahed, WT Curry, RL Martuza, DN Louis, O Rozenblatt-Rosen, ML Suvà, A Regev, BE Bernstein. Single-cell RNA-seq highlights intratumoral heterogeneity in primary glioblastoma. Science 2014; 344(6190): 1396–1401 https://doi.org/10.1126/science.1254257
pmid: 24925914
15
C Neftel, J Laffy, MG Filbin, T Hara, ME Shore, GJ Rahme, AR Richman, D Silverbush, ML Shaw, CM Hebert, J Dewitt, S Gritsch, EM Perez, Castro LN Gonzalez, X Lan, N Druck, C Rodman, D Dionne, A Kaplan, MS Bertalan, J Small, K Pelton, S Becker, D Bonal, QD Nguyen, RL Servis, JM Fung, R Mylvaganam, L Mayr, J Gojo, C Haberler, R Geyeregger, T Czech, I Slavc, BV Nahed, WT Curry, BS Carter, H Wakimoto, PK Brastianos, TT Batchelor, A Stemmer-Rachamimov, M Martinez-Lage, MP Frosch, I Stamenkovic, N Riggi, E Rheinbay, M Monje, O Rozenblatt-Rosen, DP Cahill, AP Patel, T Hunter, IM Verma, KL Ligon, DN Louis, A Regev, BE Bernstein, I Tirosh, ML Suvà. An integrative model of cellular states, plasticity, and genetics for glioblastoma. Cell 2019; 178(4): 835–849.e21 https://doi.org/10.1016/j.cell.2019.06.024
pmid: 31327527
16
TM Kim, W Huang, R Park, PJ Park, MD Johnson. A developmental taxonomy of glioblastoma defined and maintained by microRNAs. Cancer Res 2011; 71(9): 3387–3399 https://doi.org/10.1158/0008-5472.CAN-10-4117
pmid: 21385897
17
H Noushmehr, DJ Weisenberger, K Diefes, HS Phillips, K Pujara, BP Berman, F Pan, CE Pelloski, EP Sulman, KP Bhat, RG Verhaak, KA Hoadley, DN Hayes, CM Perou, HK Schmidt, L Ding, RK Wilson, Den Berg D Van, H Shen, H Bengtsson, P Neuvial, LM Cope, J Buckley, JG Herman, SB Baylin, PW Laird, K; Cancer Genome Atlas Research Network Aldape. Identification of a CpG island methylator phenotype that defines a distinct subgroup of glioma. Cancer Cell 2010; 17(5): 510–522 https://doi.org/10.1016/j.ccr.2010.03.017
pmid: 20399149
18
Y Sun, W Zhang, D Chen, Y Lv, J Zheng, H Lilljebjörn, L Ran, Z Bao, C Soneson, HO Sjögren, LG Salford, J Ji, PJ French, T Fioretos, T Jiang, X Fan. A glioma classification scheme based on coexpression modules of EGFR and PDGFRA. Proc Natl Acad Sci USA 2014; 111(9): 3538–3543 https://doi.org/10.1073/pnas.1313814111
pmid: 24550449
19
J Li, Y Xue, A Wenger, Y Sun, Z Wang, C Zhang, Y Zhang, B Fekete, B Rydenhag, AS Jakola, T Jiang, H Carén, X Fan. Individual assignment of adult diffuse gliomas into the EM/PM molecular subtypes using a TaqMan low-density array. Clin Cancer Res 2019; 25(23): 7068–7077 https://doi.org/10.1158/1078-0432.CCR-19-0299
pmid: 31481507
20
HS Phillips, S Kharbanda, R Chen, WF Forrest, RH Soriano, TD Wu, A Misra, JM Nigro, H Colman, L Soroceanu, PM Williams, Z Modrusan, BG Feuerstein, K Aldape. Molecular subclasses of high-grade glioma predict prognosis, delineate a pattern of disease progression, and resemble stages in neurogenesis. Cancer Cell 2006; 9(3): 157–173 https://doi.org/10.1016/j.ccr.2006.02.019
pmid: 16530701
21
SM Kwon, SH Kang, CK Park, S Jung, ES Park, JS Lee, SH Kim, HG Woo. Recurrent glioblastomas reveal molecular subtypes associated with mechanistic implications of drug-resistance. PLoS One 2015; 10(10): e0140528 https://doi.org/10.1371/journal.pone.0140528
pmid: 26466313
22
KM Joo, J Kim, J Jin, M Kim, HJ Seol, J Muradov, H Yang, YL Choi, WY Park, DS Kong, JI Lee, YH Ko, HG Woo, J Lee, S Kim, DH Nam. Patient-specific orthotopic glioblastoma xenograft models recapitulate the histopathology and biology of human glioblastomas in situ. Cell Rep 2013; 3(1): 260–273 https://doi.org/10.1016/j.celrep.2012.12.013
pmid: 23333277
23
J Kim, IH Lee, HJ Cho, CK Park, YS Jung, Y Kim, SH Nam, BS Kim, MD Johnson, DS Kong, HJ Seol, JI Lee, KM Joo, Y Yoon, WY Park, J Lee, PJ Park, DH Nam. Spatiotemporal evolution of the primary glioblastoma genome. Cancer Cell 2015; 28(3): 318–328 https://doi.org/10.1016/j.ccell.2015.07.013
pmid: 26373279
24
RB Puchalski, N Shah, J Miller, R Dalley, SR Nomura, JG Yoon, KA Smith, M Lankerovich, D Bertagnolli, K Bickley, AF Boe, K Brouner, S Butler, S Caldejon, M Chapin, S Datta, N Dee, T Desta, T Dolbeare, N Dotson, A Ebbert, D Feng, X Feng, M Fisher, G Gee, J Goldy, L Gourley, BW Gregor, G Gu, N Hejazinia, J Hohmann, P Hothi, R Howard, K Joines, A Kriedberg, L Kuan, C Lau, F Lee, H Lee, T Lemon, F Long, N Mastan, E Mott, C Murthy, K Ngo, E Olson, M Reding, Z Riley, D Rosen, D Sandman, N Shapovalova, CR Slaughterbeck, A Sodt, G Stockdale, A Szafer, W Wakeman, PE Wohnoutka, SJ White, D Marsh, RC Rostomily, L Ng, C Dang, A Jones, B Keogh, HR Gittleman, JS Barnholtz-Sloan, PJ Cimino, MS Uppin, CD Keene, FR Farrokhi, JD Lathia, ME Berens, A Iavarone, A Bernard, E Lein, JW Phillips, SW Rostad, C Cobbs, MJ Hawrylycz, GD Foltz. An anatomic transcriptional atlas of human glioblastoma. Science 2018; 360(6389): 660–663 https://doi.org/10.1126/science.aaf2666
pmid: 29748285
25
D Mizrak, HM Levitin, AC Delgado, V Crotet, J Yuan, Z Chaker, V Silva-Vargas, PA Sims, F Doetsch. Single-cell analysis of regional differences in adult V-SVZ neural stem cell lineages. Cell Rep 2019; 26(2): 394–406.e5 https://doi.org/10.1016/j.celrep.2018.12.044
pmid: 30625322
26
I Tirosh, AS Venteicher, C Hebert, LE Escalante, AP Patel, K Yizhak, JM Fisher, C Rodman, C Mount, MG Filbin, C Neftel, N Desai, J Nyman, B Izar, CC Luo, JM Francis, AA Patel, ML Onozato, N Riggi, KJ Livak, D Gennert, R Satija, BV Nahed, WT Curry, RL Martuza, R Mylvaganam, AJ Iafrate, MP Frosch, TR Golub, MN Rivera, G Getz, O Rozenblatt-Rosen, DP Cahill, M Monje, BE Bernstein, DN Louis, A Regev, ML Suvà. Single-cell RNA-seq supports a developmental hierarchy in human oligodendroglioma. Nature 2016; 539(7628): 309–313 https://doi.org/10.1038/nature20123
pmid: 27806376
27
S Darmanis, SA Sloan, D Croote, M Mignardi, S Chernikova, P Samghababi, Y Zhang, N Neff, M Kowarsky, C Caneda, G Li, SD Chang, ID Connolly, Y Li, BA Barres, MH Gephart, SR Quake. Single-cell RNA-Seq analysis of infiltrating neoplastic cells at the migrating front of human glioblastoma. Cell Rep 2017; 21(5): 1399–1410 https://doi.org/10.1016/j.celrep.2017.10.030
pmid: 29091775
28
AS Venteicher, I Tirosh, C Hebert, K Yizhak, C Neftel, MG Filbin, V Hovestadt, LE Escalante, ML Shaw, C Rodman, SM Gillespie, D Dionne, CC Luo, H Ravichandran, R Mylvaganam, C Mount, ML Onozato, BV Nahed, H Wakimoto, WT Curry, AJ Iafrate, MN Rivera, MP Frosch, TR Golub, PK Brastianos, G Getz, AP Patel, M Monje, DP Cahill, O Rozenblatt-Rosen, DN Louis, BE Bernstein, A Regev, ML Suvà. Decoupling genetics, lineages, and microenvironment in IDH-mutant gliomas by single-cell RNA-seq. Science 2017; 355(6332): eaai8478 https://doi.org/10.1126/science.aai8478
pmid: 28360267
29
W Huang, BT Sherman, RA Lempicki. Systematic and integrative analysis of large gene lists using DAVID bioinformatics resources. Nat Protoc 2009; 4(1): 44–57 https://doi.org/10.1038/nprot.2008.211
pmid: 19131956
30
W Huang, BT Sherman, RA Lempicki. Bioinformatics enrichment tools: paths toward the comprehensive functional analysis of large gene lists. Nucleic Acids Res 2009; 37(1): 1–13 https://doi.org/10.1093/nar/gkn923
pmid: 19033363
31
R Beroukhim, G Getz, L Nghiemphu, J Barretina, T Hsueh, D Linhart, I Vivanco, JC Lee, JH Huang, S Alexander, J Du, T Kau, RK Thomas, K Shah, H Soto, S Perner, J Prensner, RM Debiasi, F Demichelis, C Hatton, MA Rubin, LA Garraway, SF Nelson, L Liau, PS Mischel, TF Cloughesy, M Meyerson, TA Golub, ES Lander, IK Mellinghoff, WR Sellers. Assessing the significance of chromosomal aberrations in cancer: methodology and application to glioma. Proc Natl Acad Sci USA 2007; 104(50): 20007–20012 https://doi.org/10.1073/pnas.0710052104
pmid: 18077431
32
P Tamayo, D Scanfeld, BL Ebert, MA Gillette, CW Roberts, JP Mesirov. Metagene projection for cross-platform, cross-species characterization of global transcriptional states. Proc Natl Acad Sci USA 2007; 104(14): 5959–5964 https://doi.org/10.1073/pnas.0701068104
pmid: 17389406
33
Y Zhang, J Li, K Yi, J Feng, Z Cong, Z Wang, Y Wei, F Wu, W Cheng, AA Samo, P Salomoni, Q Yang, Y Huang, C Kang, T Jiang, X Fan. Elevated signature of a gene module coexpressed with CDC20 marks genomic instability in glioma. Proc Natl Acad Sci USA 2019; 116(14): 6975–6984 https://doi.org/10.1073/pnas.1814060116
pmid: 30877245
34
E Talevich, AH Shain, T Botton, BC Bastian. CNVkit: genome-wide copy number detection and visualization from targeted DNA sequencing. PLOS Comput Biol 2016; 12(4): e1004873 https://doi.org/10.1371/journal.pcbi.1004873
pmid: 27100738
35
DC Koboldt, DE Larson, RK Wilson. Using VarScan 2 for germline variant calling and somatic mutation detection. Curr Protoc Bioinformatics 2013; 44(1): 15.4.1–15.4.17 https://doi.org/10.1002/0471250953.bi1504s44
pmid: 25553206
36
A Butler, P Hoffman, P Smibert, E Papalexi, R Satija. Integrating single-cell transcriptomic data across different conditions, technologies, and species. Nat Biotechnol 2018; 36(5): 411–420 https://doi.org/10.1038/nbt.4096
pmid: 29608179
37
J Yuan, HM Levitin, V Frattini, EC Bush, DM Boyett, J Samanamud, M Ceccarelli, A Dovas, G Zanazzi, P Canoll, JN Bruce, A Lasorella, A Iavarone, PA Sims. Single-cell transcriptome analysis of lineage diversity in high-grade glioma. Genome Med 2018; 10(1): 57 https://doi.org/10.1186/s13073-018-0567-9
pmid: 30041684
38
Y Zhang, K Chen, SA Sloan, ML Bennett, AR Scholze, S O’Keeffe, HP Phatnani, P Guarnieri, C Caneda, N Ruderisch, S Deng, SA Liddelow, C Zhang, R Daneman, T Maniatis, BA Barres, JQ Wu. An RNA-sequencing transcriptome and splicing database of glia, neurons, and vascular cells of the cerebral cortex. J Neurosci 2014; 34(36): 11929–11947 https://doi.org/10.1523/JNEUROSCI.1860-14.2014
pmid: 25186741
39
S Marques, A Zeisel, S Codeluppi, Bruggen D van, Falcão A Mendanha, L Xiao, H Li, M Häring, H Hochgerner, RA Romanov, D Gyllborg, Manchado A Muñoz, Manno G La, P Lönnerberg, EM Floriddia, F Rezayee, P Ernfors, E Arenas, J Hjerling-Leffler, T Harkany, WD Richardson, S Linnarsson, G Castelo-Branco. Oligodendrocyte heterogeneity in the mouse juvenile and adult central nervous system. Science 2016; 352(6291): 1326–1329 https://doi.org/10.1126/science.aaf6463
pmid: 27284195
40
ML Bennett, FC Bennett, SA Liddelow, B Ajami, JL Zamanian, NB Fernhoff, SB Mulinyawe, CJ Bohlen, A Adil, A Tucker, IL Weissman, EF Chang, G Li, GA Grant, MG Hayden Gephart, BA Barres. New tools for studying microglia in the mouse and human CNS. Proc Natl Acad Sci USA 2016; 113(12): E1738–E1746 https://doi.org/10.1073/pnas.1525528113
pmid: 26884166
41
VM RaviN NeidertP WillK JosephJP MaierJ KückelhausL VollmerJM GoeldnerSP BehringerF SchererM BoerriesM FolloT WeissD DelevJ KernbachP FrancoN SchallnerC DierksMS CarroUG HofmannC FungJ BeckR SankowskiM PrinzO SchnellHeiland D Henrik. Lineage and spatial mapping of glioblastoma-associated immunity. bioRxiv, 2020: p. 2020.06.01.121467 doi:10.1101/2020.06.01.121467
42
JD Cahoy, B Emery, A Kaushal, LC Foo, JL Zamanian, KS Christopherson, Y Xing, JL Lubischer, PA Krieg, SA Krupenko, WJ Thompson, BA Barres. A transcriptome database for astrocytes, neurons, and oligodendrocytes: a new resource for understanding brain development and function. J Neurosci 2008; 28(1): 264–278 https://doi.org/10.1523/JNEUROSCI.4178-07.2008
pmid: 18171944
43
AM Newman, CB Steen, CL Liu, AJ Gentles, AA Chaudhuri, F Scherer, MS Khodadoust, MS Esfahani, BA Luca, D Steiner, M Diehn, AA Alizadeh. Determining cell type abundance and expression from bulk tissues with digital cytometry. Nat Biotechnol 2019; 37(7): 773–782 https://doi.org/10.1038/s41587-019-0114-2
pmid: 31061481
44
D Szklarczyk, AL Gable, D Lyon, A Junge, S Wyder, J Huerta-Cepas, M Simonovic, NT Doncheva, JH Morris, P Bork, LJ Jensen, CV Mering. STRING v11: protein-protein association networks with increased coverage, supporting functional discovery in genome-wide experimental datasets. Nucleic Acids Res 2019; 47(D1): D607–D613 https://doi.org/10.1093/nar/gky1131
pmid: 30476243
45
S Madhavan, JC Zenklusen, Y Kotliarov, H Sahni, HA Fine, K Buetow. Rembrandt: helping personalized medicine become a reality through integrative translational research. Mol Cancer Res 2009; 7(2): 157–167 https://doi.org/10.1158/1541-7786.MCR-08-0435
pmid: 19208739
46
H Suzuki, K Aoki, K Chiba, Y Sato, Y Shiozawa, Y Shiraishi, T Shimamura, A Niida, K Motomura, F Ohka, T Yamamoto, K Tanahashi, M Ranjit, T Wakabayashi, T Yoshizato, K Kataoka, K Yoshida, Y Nagata, A Sato-Otsubo, H Tanaka, M Sanada, Y Kondo, H Nakamura, M Mizoguchi, T Abe, Y Muragaki, R Watanabe, I Ito, S Miyano, A Natsume, S Ogawa. Mutational landscape and clonal architecture in grade II and III gliomas. Nat Genet 2015; 47(5): 458–468 https://doi.org/10.1038/ng.3273
pmid: 25848751
47
Cancer Genome Atlas Research Network; Brat DJ, Verhaak RG, Aldape KD, Yung WK, Salama SR, Cooper LA, Rheinbay E, Miller CR, Vitucci M, Morozova O, Robertson AG, Noushmehr H, Laird PW, Cherniack AD, Akbani R, Huse JT, Ciriello G, Poisson LM, Barnholtz-Sloan JS, Berger MS, Brennan C, Colen RR, Colman H, Flanders AE, Giannini C, Grifford M, Iavarone A, Jain R, Joseph I, Kim J, Kasaian K, Mikkelsen T, Murray BA, O’Neill BP, Pachter L, Parsons DW, Sougnez C, Sulman EP, Vandenberg SR, Van Meir EG, von Deimling A, Zhang H, Crain D, Lau K, Mallery D, Morris S, Paulauskis J, Penny R, Shelton T, Sherman M, Yena P, Black A, Bowen J, Dicostanzo K, Gastier-Foster J, Leraas KM, Lichtenberg TM, Pierson CR, Ramirez NC, Taylor C, Weaver S, Wise L, Zmuda E, Davidsen T, Demchok JA, Eley G, Ferguson ML, Hutter CM, Mills Shaw KR, Ozenberger BA, Sheth M, Sofia HJ, Tarnuzzer R, Wang Z, Yang L, Zenklusen JC, Ayala B, Baboud J, Chudamani S, Jensen MA, Liu J, Pihl T, Raman R, Wan Y, Wu Y, Ally A, Auman JT, Balasundaram M, Balu S, Baylin SB, Beroukhim R, Bootwalla MS, Bowlby R, Bristow CA, Brooks D, Butterfield Y, Carlsen R, Carter S, Chin L, Chu A, Chuah E, Cibulskis K, Clarke A, Coetzee SG, Dhalla N, Fennell T, Fisher S, Gabriel S, Getz G, Gibbs R, Guin R, Hadjipanayis A, Hayes DN, Hinoue T, Hoadley K, Holt RA, Hoyle AP, Jefferys SR, Jones S, Jones CD, Kucherlapati R, Lai PH, Lander E, Lee S, Lichtenstein L, Ma Y, Maglinte DT, Mahadeshwar HS, Marra MA, Mayo M, Meng S, Meyerson ML, Mieczkowski PA, Moore RA, Mose LE, Mungall AJ, Pantazi A, Parfenov M, Park PJ, Parker JS, Perou CM, Protopopov A, Ren X, Roach J, Sabedot TS, Schein J, Schumacher SE, Seidman JG, Seth S, Shen H, Simons JV, Sipahimalani P, Soloway MG, Song X, Sun H, Tabak B, Tam A, Tan D, Tang J, Thiessen N, Triche T Jr, Van Den Berg DJ, Veluvolu U, Waring S, Weisenberger DJ, Wilkerson MD, Wong T, Wu J, Xi L, Xu AW, Yang L, Zack TI, Zhang J, Aksoy BA, Arachchi H, Benz C, Bernard B, Carlin D, Cho J, DiCara D, Frazer S, Fuller GN, Gao J, Gehlenborg N, Haussler D, Heiman DI, Iype L, Jacobsen A, Ju Z, Katzman S, Kim H, Knijnenburg T, Kreisberg RB, Lawrence MS, Lee W, Leinonen K, Lin P, Ling S, Liu W, Liu Y, Liu Y, Lu Y, Mills G, Ng S, Noble MS, Paull E, Rao A, Reynolds S, Saksena G, Sanborn Z, Sander C, Schultz N, Senbabaoglu Y, Shen R, Shmulevich I, Sinha R, Stuart J, Sumer SO, Sun Y, Tasman N, Taylor BS, Voet D, Weinhold N, Weinstein JN, Yang D, Yoshihara K, Zheng S, Zhang W, Zou L, Abel T, Sadeghi S, Cohen ML, Eschbacher J, Hattab EM, Raghunathan A, Schniederjan MJ, Aziz D, Barnett G, Barrett W, Bigner DD, Boice L, Brewer C, Calatozzolo C, Campos B, Carlotti CG Jr, Chan TA, Cuppini L, Curley E, Cuzzubbo S, Devine K, DiMeco F, Duell R, Elder JB, Fehrenbach A, Finocchiaro G, Friedman W, Fulop J, Gardner J, Hermes B, Herold-Mende C, Jungk C, Kendler A, Lehman NL, Lipp E, Liu O, Mandt R, McGraw M, Mclendon R, McPherson C, Neder L, Nguyen P, Noss A, Nunziata R, Ostrom QT, Palmer C, Perin A, Pollo B, Potapov A, Potapova O, Rathmell WK, Rotin D, Scarpace L, Schilero C, Senecal K, Shimmel K, Shurkhay V, Sifri S, Singh R, Sloan AE, Smolenski K, Staugaitis SM, Steele R, Thorne L, Tirapelli DP, Unterberg A, Vallurupalli M, Wang Y, Warnick R, Williams F, Wolinsky Y, Bell S, Rosenberg M, Stewart C, Huang F, Grimsby JL, Radenbaugh AJ, Zhang J. Comprehensive, integrative genomic analysis of diffuse lower-grade gliomas. N Engl J Med 2015; 372(26): 2481–2498 doi:10.1056/NEJMoa1402121 PMID:26061751
48
M Ceccarelli, FP Barthel, TM Malta, TS Sabedot, SR Salama, BA Murray, O Morozova, Y Newton, A Radenbaugh, SM Pagnotta, S Anjum, J Wang, G Manyam, P Zoppoli, S Ling, AA Rao, M Grifford, AD Cherniack, H Zhang, L Poisson, CG Jr Carlotti, DP Tirapelli, A Rao, T Mikkelsen, CC Lau, WK Yung, R Rabadan, J Huse, DJ Brat, NL Lehman, JS Barnholtz-Sloan, S Zheng, K Hess, G Rao, M Meyerson, R Beroukhim, L Cooper, R Akbani, M Wrensch, D Haussler, KD Aldape, PW Laird, DH; TCGA Research Network Gutmann, H Noushmehr, A Iavarone, RG Verhaak. Molecular profiling reveals biologically discrete subsets and pathways of progression in diffuse glioma. Cell 2016; 164(3): 550–563 https://doi.org/10.1016/j.cell.2015.12.028
pmid: 26824661
49
BE Johnson, T Mazor, C Hong, M Barnes, K Aihara, CY McLean, SD Fouse, S Yamamoto, H Ueda, K Tatsuno, S Asthana, LE Jalbert, SJ Nelson, AW Bollen, WC Gustafson, E Charron, WA Weiss, IV Smirnov, JS Song, AB Olshen, S Cha, Y Zhao, RA Moore, AJ Mungall, SJM Jones, M Hirst, MA Marra, N Saito, H Aburatani, A Mukasa, MS Berger, SM Chang, BS Taylor, JF Costello. Mutational analysis reveals the origin and therapy-driven evolution of recurrent glioma. Science 2014; 343(6167): 189–193 https://doi.org/10.1126/science.1239947
pmid: 24336570
50
FP Barthel, KC Johnson, FS Varn, AD Moskalik, G Tanner, E Kocakavuk, KJ Anderson, O Abiola, K Aldape, KD Alfaro, D Alpar, SB Amin, DM Ashley, P Bandopadhayay, JS Barnholtz-Sloan, R Beroukhim, C Bock, PK Brastianos, DJ Brat, AR Brodbelt, AF Bruns, KR Bulsara, A Chakrabarty, A Chakravarti, JH Chuang, EB Claus, EJ Cochran, J Connelly, JF Costello, G Finocchiaro, MN Fletcher, PJ French, HK Gan, MR Gilbert, PV Gould, MR Grimmer, A Iavarone, A Ismail, MD Jenkinson, M Khasraw, H Kim, MCM Kouwenhoven, PS LaViolette, M Li, P Lichter, KL Ligon, AK Lowman, TM Malta, T Mazor, KL McDonald, AM Molinaro, DH Nam, N Nayyar, HK Ng, CY Ngan, SP Niclou, JM Niers, H Noushmehr, J Noorbakhsh, DR Ormond, CK Park, LM Poisson, R Rabadan, B Radlwimmer, G Rao, G Reifenberger, JK Sa, M Schuster, BL Shaw, SC Short, PAS Smitt, AE Sloan, M Smits, H Suzuki, G Tabatabai, Meir EG Van, C Watts, M Weller, P Wesseling, BA Westerman, G Widhalm, A Woehrer, WKA Yung, G Zadeh, JT Huse, Groot JF De, LF Stead, RGW Verhaak, FP Barthel, KC Johnson, FS Varn, AD Moskalik, G Tanner, E Kocakavuk, KJ Anderson, K Aldape, KD Alfaro, SB Amin, DM Ashley, P Bandopadhayay, JS Barnholtz-Sloan, R Beroukhim, C Bock, PK Brastianos, DJ Brat, AR Brodbelt, KR Bulsara, A Chakrabarty, JH Chuang, EB Claus, EJ Cochran, J Connelly, JF Costello, G Finocchiaro, MN Fletcher, PJ French, HK Gan, MR Gilbert, PV Gould, A Iavarone, A Ismail, MD Jenkinson, M Khasraw, H Kim, MCM Kouwenhoven, PS LaViolette, P Lichter, KL Ligon, AK Lowman, TM Malta, KL McDonald, AM Molinaro, DH Nam, HK Ng, SP Niclou, JM Niers, H Noushmehr, DR Ormond, CK Park, LM Poisson, R Rabadan, B Radlwimmer, G Rao, G Reifenberger, JK Sa, SC Short, PAS Smitt, AE Sloan, M Smits, H Suzuki, G Tabatabai, Meir EG Van, C Watts, M Weller, P Wesseling, BA Westerman, A Woehrer, WKA Yung, G Zadeh, JT Huse, Groot JF De, LF Stead, RGW; GLASS Consortium Verhaak. Longitudinal molecular trajectories of diffuse glioma in adults. Nature 2019; 576(7785): 112–120 https://doi.org/10.1038/s41586-019-1775-1
pmid: 31748746
51
JK Lee, J Wang, JK Sa, E Ladewig, HO Lee, IH Lee, HJ Kang, DS Rosenbloom, PG Camara, Z Liu, P van Nieuwenhuizen, SW Jung, SW Choi, J Kim, A Chen, KT Kim, S Shin, YJ Seo, JM Oh, YJ Shin, CK Park, DS Kong, HJ Seol, A Blumberg, JI Lee, A Iavarone, WY Park, R Rabadan, DH Nam. Spatiotemporal genomic architecture informs precision oncology in glioblastoma. Nat Genet 2017; 49(4): 594–599 https://doi.org/10.1038/ng.3806
pmid: 28263318
52
K Draaisma, A Chatzipli, M Taphoorn, M Kerkhof, A Weyerbrock, M Sanson, A Hoeben, S Lukacova, G Lombardi, S Leenstra, M Hanse, R Fleischeuer, C Watts, J McAbee, N Angelopoulos, T Gorlia, V Golfinopoulos, JM Kros, RGW Verhaak, V Bours, MJ van den Bent, U McDermott, PA Robe, PJ French. Molecular evolution of IDH wild-type glioblastomas treated with standard of care affects survival and design of precision medicine trials: a report from the EORTC 1542 study. J Clin Oncol 2020; 38(1): 81–99 https://doi.org/10.1200/JCO.19.00367
pmid: 31743054
53
RC Gimple, RL Kidwell, LJY Kim, T Sun, AD Gromovsky, Q Wu, M Wolf, D Lv, S Bhargava, L Jiang, BC Prager, X Wang, Q Ye, Z Zhu, G Zhang, Z Dong, L Zhao, D Lee, J Bi, AE Sloan, PS Mischel, JM Brown, H Cang, T Huan, SC Mack, Q Xie, JN Rich. Glioma stem cell-specific superenhancer promotes polyunsaturated fatty-acid synthesis to support EGFR signaling. Cancer Discov 2019; 9(9): 1248–1267 https://doi.org/10.1158/2159-8290.CD-19-0061
pmid: 31201181
54
A López-Juárez, HE Titus, SH Silbak, JW Pressler, TA Rizvi, M Bogard, MR Bennett, G Ciraolo, MT Williams, CV Vorhees, N Ratner. Oligodendrocyte Nf1 controls aberrant notch activation and regulates myelin structure and behavior. Cell Rep 2017; 19(3): 545–557 https://doi.org/10.1016/j.celrep.2017.03.073
pmid: 28423318
55
H Kim, S Zheng, SS Amini, SM Virk, T Mikkelsen, DJ Brat, J Grimsby, C Sougnez, F Muller, J Hu, AE Sloan, ML Cohen, EG Van Meir, L Scarpace, PW Laird, JN Weinstein, ES Lander, S Gabriel, G Getz, M Meyerson, L Chin, JS Barnholtz-Sloan, RG Verhaak. Whole-genome and multisector exome sequencing of primary and post-treatment glioblastoma reveals patterns of tumor evolution. Genome Res 2015; 25(3): 316–327 https://doi.org/10.1101/gr.180612.114
pmid: 25650244
56
C Yang, Y Tan, S Li, J Zhou, Q Wang, Y Wang, Y Xie, L Chen, J Li, C Fang, C Kang. Genomic landscapes by multiregion sequencing combined with circulation tumor DNA detection contribute to molecular diagnosis in glioblastomas. Aging (Albany NY) 2019; 11(23): 11224–11243 https://doi.org/10.18632/aging.102526
pmid: 31822636
57
K Yu, Y Hu, F Wu, Q Guo, Z Qian, W Hu, J Chen, K Wang, X Fan, X Wu, JE Rasko, X Fan, A Iavarone, T Jiang, F Tang, XD Su. Surveying brain tumor heterogeneity by single-cell RNA-sequencing of multi-sector biopsies. Natl Sci Rev 2020; 7(8): 1306–1318 https://doi.org/10.1093/nsr/nwaa099
pmid: 34692159
58
Z Chaker, P Codega, F Doetsch. A mosaic world: puzzles revealed by adult neural stem cell heterogeneity. Wiley Interdiscip Rev Dev Biol 2016; 5(6): 640–658 https://doi.org/10.1002/wdev.248
pmid: 27647730
59
B Menn, JM Garcia-Verdugo, C Yaschine, O Gonzalez-Perez, D Rowitch, A Alvarez-Buylla. Origin of oligodendrocytes in the subventricular zone of the adult brain. J Neurosci 2006; 26(30): 7907–7918 https://doi.org/10.1523/JNEUROSCI.1299-06.2006
pmid: 16870736
60
M Snuderl, L Fazlollahi, LP Le, M Nitta, BH Zhelyazkova, CJ Davidson, S Akhavanfard, DP Cahill, KD Aldape, RA Betensky, DN Louis, AJ Iafrate. Mosaic amplification of multiple receptor tyrosine kinase genes in glioblastoma. Cancer Cell 2011; 20(6): 810–817 https://doi.org/10.1016/j.ccr.2011.11.005
pmid: 22137795
61
NJ Szerlip, A Pedraza, D Chakravarty, M Azim, J McGuire, Y Fang, T Ozawa, EC Holland, JT Huse, S Jhanwar, MA Leversha, T Mikkelsen, CW Brennan. Intratumoral heterogeneity of receptor tyrosine kinases EGFR and PDGFRA amplification in glioblastoma defines subpopulations with distinct growth factor response. Proc Natl Acad Sci USA 2012; 109(8): 3041–3046 https://doi.org/10.1073/pnas.1114033109
pmid: 22323597
E Kougioumtzidou, T Shimizu, NB Hamilton, K Tohyama, R Sprengel, H Monyer, D Attwell, WD Richardson. Signalling through AMPA receptors on oligodendrocyte precursors promotes myelination by enhancing oligodendrocyte survival. eLife 2017; 6: e28080 https://doi.org/10.7554/eLife.28080
pmid: 28608780
64
VA LarsonY ZhangDE Bergles. Electrophysiological properties of NG2(+) cells: matching physiological studies with gene expression profiles. Brain Res 2016; 1638(Pt B): 138–160 doi:10.1016/j.brainres.2015.09.010
pmid: 26385417
65
M Castellan, A Guarnieri, A Fujimura, F Zanconato, G Battilana, T Panciera, HL Sladitschek, P Contessotto, A Citron, A Grilli, O Romano, S Bicciato, M Fassan, E Porcù, A Rosato, M Cordenonsi, S Piccolo. Single-cell analyses reveal YAP/TAZ as regulators of stemness and cell plasticity in glioblastoma. Nat Can 2021; 2(2): 174–188 https://doi.org/10.1038/s43018-020-00150-z
pmid: 33644767
66
L Garofano, S Migliozzi, YT Oh, F D’Angelo, RD Najac, A Ko, B Frangaj, FP Caruso, K Yu, J Yuan, W Zhao, Di Stefano A Luisa, F Bielle, T Jiang, P Sims, ML Suvà, F Tang, XD Su, M Ceccarelli, M Sanson, A Lasorella, A Iavarone. Pathway-based classification of glioblastoma uncovers a mitochondrial subtype with therapeutic vulnerabilities. Nat Can 2021; 2(2): 141–156 https://doi.org/10.1038/s43018-020-00159-4
pmid: 33681822
67
GP Dunn, ML Rinne, J Wykosky, G Genovese, SN Quayle, IF Dunn, PK Agarwalla, MG Chheda, B Campos, A Wang, C Brennan, KL Ligon, F Furnari, WK Cavenee, RA Depinho, L Chin, WC Hahn. Emerging insights into the molecular and cellular basis of glioblastoma. Genes Dev 2012; 26(8): 756–784 https://doi.org/10.1101/gad.187922.112
pmid: 22508724
68
E Pastrana, LC Cheng, F Doetsch. Simultaneous prospective purification of adult subventricular zone neural stem cells and their progeny. Proc Natl Acad Sci USA 2009; 106(15): 6387–6392 https://doi.org/10.1073/pnas.0810407106
pmid: 19332781
69
S Alcantara Llaguno, D Sun, AM Pedraza, E Vera, Z Wang, DK Burns, LF Parada. Cell-of-origin susceptibility to glioblastoma formation declines with neural lineage restriction. Nat Neurosci 2019; 22(4): 545–555 https://doi.org/10.1038/s41593-018-0333-8
pmid: 30778149