NEW: astrocytoma IV (formerly secondary glioblastoma) and GBM
WHO classification: introducing astrocytoma IV and molecular definition of GBM (even without typical histological features)
CTC: circulating tumor cell; EV: extracellular vesicle; PNETs: primitive neuroectodermal tumors; SSCP: single-strand conformation polymorphism; PA I: pleomorphic adenoma I; PCR: polymerase chain reaction; ctDNA: circulating tumor DNA; MGMT: O6-methylguanine-methyltransferase; cfDNA: cell-free DNA; NSCLC: non-small cell lung cancer; FDA: Food and Drug administration; WHO: World Health Organization
Declarations
Acknowledgments
We gratefully acknowledge the introduction into the field of brain tumor research by Otmar D. Wiestler and the late Paul Kleihues, as well as discussions with Irving L. Weissman and Eugene C. Butcher on immune and tumor cell migration and metastasis, and Catherine Alix-Panabières on liquid biopsy.
Author contributions
RHE: Conceptualization, Investigation, Writing—original draft, Writing—review & editing. MS: Conceptualization, Investigation, Writing—review & editing. Both of the authors read and approved the submitted version.
Conflicts of interest
The authors declare that they have no conflicts of interest.
Ohgaki H, Kleihues P.Genetic pathways to primary and secondary glioblastoma. Am J Pathol. 2007;170:1445–53. [DOI] [PubMed] [PMC]
Ostrom QT, Cioffi G, Waite K, Kruchko C, Barnholtz-Sloan JS.CBTRUS statistical report: primary brain and other central nervous system tumors diagnosed in the United States in 2014–2018. Neuro Oncol. 2021;23:iii1–105. [DOI] [PubMed] [PMC]
Bailey P, Cushing H.A classification of the tumours of the glioma group on a histogenetic basis, with a correlated study of prognosis. Philadelphia, London [etc.]: J. B. Lippincott Company; 1926.
Louis DN, Perry A, Reifenberger G, von Deimling A, Figarella-Branger D, Cavenee WK, et al. The 2016 World Health Organization Classification of Tumors of the Central Nervous System: a summary. Acta Neuropathol (Berl). 2016;131:803–20. [DOI] [PubMed]
Louis DN, Perry A, Wesseling P, Brat DJ, Cree IA, Figarella-Branger D, et al. The 2021 WHO Classification of Tumors of the Central Nervous System: a summary. Neuro Oncol. 2021;23:1231–51. [DOI] [PubMed] [PMC]
Watanabe K, Tachibana O, Sato K, Yonekawa Y, Kleihues P, Ohgaki H.Overexpression of the EGF Receptor and p53 Mutations are Mutually Exclusive in the Evolution of Primary and Secondary Glioblastomas. Brain Pathol. 1996;6:217–23. [DOI] [PubMed]
Eibl RH, Wiestler OD.Induction of primitive neuroectodermal tumors following retrovirus-mediated transfer of SV40 large T antigen into neural transplants. Clin Neuropathol. 1991;10:245.
Eibl RH, Kleihues P, Jat PS, Wiestler OD.A model for primitive neuroectodermal tumors in transgenic neural transplants harboring the SV40 large T antigen. Am J Pathol. 1994;144:556–64. [PubMed] [PMC]
Wiestler OD, Aguzzi A, Schneemann M, Eibl R, von Deimling A, Kleihues P.Oncogene complementation in fetal brain transplants. Cancer Res. 1992;52:3760–7. [PubMed]
Eibl RH, Schneemann M.Medulloblastoma: from TP53 mutations to molecular classification and liquid biopsy. Biology. 2023;12:267. [DOI]
von Deimling A, Eibl RH, Ohgaki H, Louis DN, von Ammon K, Petersen I, et al. p53 mutations are associated with 17p allelic loss in grade II and grade III astrocytoma. Cancer Res. 1992;52:2987–90. [PubMed]
Louis DN, von Deimling A, Chung RY, Rubio MP, Whaley JM, Eibl RH, et al. Comparative study of p53 gene and protein alterations in human astrocytic tumors. J Neuropathol Exp Neurol. 1993;52:31–8. [DOI] [PubMed]
Ohgaki H, Eibl RH, Schwab M, Reichel MB, Mariani L, Gehring M, et al. Mutations of the p53 tumor suppressor gene in neoplasms of the human nervous system. Mol Carcinog. 1993;8:74–80. [DOI] [PubMed]
Balaña C, Ramirez JL, Taron M, Roussos Y, Ariza A, Ballester R, et al. O6-methyl-guanine-DNA methyltransferase methylation in serum and tumor DNA predicts response to 1,3-bis(2-chloroethyl)-1-nitrosourea but not to temozolamide plus cisplatin in glioblastoma multiforme. Clin Cancer Res. 2003;9:1461–8. [PubMed]
Bettegowda C, Sausen M, Leary RJ, Kinde I, Wang Y, Agrawal N, et al. Detection of circulating tumor DNA in early- and late-stage human malignancies. Sci Transl Med. 2014;6:224ra24. [DOI] [PubMed] [PMC]
Sullivan JP, Nahed BV, Madden MW, Oliveira SM, Springer S, Bhere D, et al. Brain tumor cells in circulation are enriched for mesenchymal gene expression. Cancer Discov. 2014;4:1299–309. [DOI] [PubMed] [PMC]
Underhill HR, Kitzman JO, Hellwig S, Welker NC, Daza R, Baker DN, et al. Fragment length of circulating tumor DNA. PLoS Genet. 2016;12:e1006162. [DOI] [PubMed] [PMC]
Donaldson J, Park BH.Circulating tumor DNA: measurement and clinical utility. Annu Rev Med. 2018;69:223–34. [DOI] [PubMed]
Yasui T, Yanagida T, Ito S, Konakade Y, Takeshita D, Naganawa T, et al. Unveiling massive numbers of cancer-related urinary-microRNA candidates via nanowires. Sci Adv. 2017;3:e1701133. [DOI] [PubMed] [PMC]
Aslan K, Turco V, Blobner J, Sonner JK, Liuzzi AR, Núñez NG, et al. Heterogeneity of response to immune checkpoint blockade in hypermutated experimental gliomas. Nat Commun. 2020;11:931. [DOI] [PubMed] [PMC]
Martínez-Ricarte F, Mayor R, Martínez-Sáez E, Rubio-Pérez C, Pineda E, Cordero E, et al. Molecular diagnosis of diffuse gliomas through sequencing of cell-free circulating tumor DNA from cerebrospinal fluid. Clin Cancer Res. 2018;24:2812–9. [DOI] [PubMed]
Miller AM, Shah RH, Pentsova EI, Pourmaleki M, Briggs S, Distefano N, et al. Tracking tumour evolution in glioma through liquid biopsies of cerebrospinal fluid. Nature. 2019;565:654–8. [DOI] [PubMed] [PMC]
Mouliere F, Mair R, Chandrananda D, Marass F, Smith CG, Su J, et al. Detection of cell-free DNA fragmentation and copy number alterations in cerebrospinal fluid from glioma patients. EMBO Mol Med. 2018;10:e9323. [DOI] [PubMed] [PMC]
Pan Y, Long W, Liu Q.Current advances and future perspectives of cerebrospinal fluid biopsy in midline brain malignancies. Curr Treat Options Oncol. 2019;20:88. [DOI] [PubMed]
Wang Y, Springer S, Zhang M, McMahon KW, Kinde I, Dobbyn L, et al. Detection of tumor-derived DNA in cerebrospinal fluid of patients with primary tumors of the brain and spinal cord. Proc Natl Acad Sci U S A. 2015;112:9704–9. [DOI] [PubMed] [PMC]
De Mattos-Arruda L, Mayor R, Ng CKY, Weigelt B, Martínez-Ricarte F, Torrejon D, et al. Cerebrospinal fluid-derived circulating tumour DNA better represents the genomic alterations of brain tumours than plasma. Nat Commun. 2015;6:8839. [DOI] [PubMed] [PMC]
Majchrzak-Celińska A, Paluszczak J, Kleszcz R, Magiera M, Barciszewska A-M, Nowak S, et al. Detection of MGMT, RASSF1A, p15INK4B, and p14ARF promoter methylation in circulating tumor-derived DNA of central nervous system cancer patients. J Appl Genet. 2013;54:335–44. [DOI] [PubMed] [PMC]
Preuss I, Eberhagen I, Haas S, Eibl RH, Kaufmann M, von Minckwitz G, et al. O6-methylguanine-DNA methyltransferase activity in breast and brain tumors. Int J Cancer. 1995;61:321–6. [DOI] [PubMed]
Preuss I, Haas S, Eichhorn U, Eberhagen I, Kaufmann M, Beck T, et al. Activity of the DNA repair protein O6-methylguanine-DNA methyltransferase in human tumor and corresponding normal tissue. Cancer Detect Prev. 1996;20:130–6. [PubMed]
Kalogerak A, Tamiolakis D, Zoi I, Karvela-Kalogeraki I, Karvelas-Kalogerakis M, Segredakis J, et al. FNA Cytology in pediatric small cell glioblastoma. Acta Biomed. 2018;89:265–8. [DOI] [PubMed] [PMC]
Weaver KD, Grossman SA, Herman JG.Methylated tumor-specific DNA as a plasma biomarker in patients with glioma. Cancer Invest. 2006;24:35–40. [DOI] [PubMed]
Lavon I, Refael M, Zelikovitch B, Shalom E, Siegal T.Serum DNA can define tumor-specific genetic and epigenetic markers in gliomas of various grades. Neuro Oncol. 2010;12:173–80. [DOI] [PubMed] [PMC]
Boisselier B, Gállego Pérez-Larraya J, Rossetto M, Labussière M, Ciccarino P, Marie Y, et al. Detection of IDH1 mutation in the plasma of patients with glioma. Neurology. 2012;79:1693–8. [DOI] [PubMed]
Schwaederle M, Chattopadhyay R, Kato S, Fanta PT, Banks KC, Choi IS, et al. Genomic alterations in circulating tumor DNA from diverse cancer patients identified by next-generation sequencing. Cancer Res. 2017;77:5419–27. [DOI] [PubMed] [PMC]
Juratli TA, Stasik S, Zolal A, Schuster C, Richter S, Daubner D, et al. TERT promoter mutation detection in cell-free tumor-derived DNA in patients with IDH wild-type glioblastomas: A Pilot Prospective Study. Clin Cancer Res. 2018;24:5282–91. [DOI] [PubMed]
Piccioni DE, Achrol AS, Kiedrowski LA, Banks KC, Boucher N, Barkhoudarian G, et al. Analysis of cell-free circulating tumor DNA in 419 patients with glioblastoma and other primary brain tumors. CNS Oncol. 2019;8:CNS34. [DOI] [PubMed] [PMC]
Saenz-Antoñanzas A, Auzmendi-Iriarte J, Carrasco-Garcia E, Moreno-Cugnon L, Ruiz I, Villanua J, et al. Liquid biopsy in glioblastoma: opportunities, applications and challenges. Cancers (Basel). 2019;11:950. [DOI] [PubMed] [PMC]
Gatto L, Franceschi E, Di Nunno V, Tosoni A, Lodi R, Brandes AA.Liquid biopsy in glioblastoma management: from current research to future perspectives. Oncologist. 2021;26:865–78. [DOI] [PubMed] [PMC]
Ronvaux L, Riva M, Coosemans A, Herzog M, Rommelaere G, Donis N, et al. Liquid biopsy in glioblastoma. Cancers (Basel). 2022;14:3394. [DOI] [PubMed] [PMC]
Soffietti R, Bettegowda C, Mellinghoff IK, Warren KE, Ahluwalia MS, De Groot JF, et al. Liquid biopsy in gliomas: A RANO review and proposals for clinical applications. Neuro Oncol. 2022;24:855–71. [DOI] [PubMed] [PMC]
Blee JA, Liu X, Harland AJ, Fatania K, Currie S, Kurian KM, et al. Liquid biopsies for early diagnosis of brain tumours: in silico mathematical biomarker modelling. J R Soc Interface. 2022;19:20220180. [DOI] [PubMed] [PMC]
Eibl RH, Schneemann M.Cell-free DNA as a biomarker in cancer. Extracell Vesicles Circ Nucleic Acids. 2022;3:178–98. [DOI]
Müller C, Holtschmidt J, Auer M, Heitzer E, Lamszus K, Schulte A, et al. Hematogenous dissemination of glioblastoma multiforme. Sci Transl Med. 2014;6:247ra101. [DOI]
Macarthur KM, Kao GD, Chandrasekaran S, Alonso-Basanta M, Chapman C, Lustig RA, et al. Detection of brain tumor cells in the peripheral blood by a telomerase promoter-based assay. Cancer Res. 2014;74:2152–9. [DOI] [PubMed] [PMC]
Krol I, Castro-Giner F, Maurer M, Gkountela S, Szczerba BM, Scherrer R, et al. Detection of circulating tumour cell clusters in human glioblastoma. Br J Cancer. 2018;119:487–91. [DOI] [PubMed] [PMC]
Gao F, Cui Y, Jiang H, Sui D, Wang Y, Jiang Z, et al. Circulating tumor cell is a common property of brain glioma and promotes the monitoring system. Oncotarget. 2016;7:71330–40. [DOI] [PubMed] [PMC]
Eibl RH, Pietsch T, Moll J, Skroch-Angel P, Heider KH, von Ammon K, et al. Expression of variant CD44 epitopes in human astrocytic brain tumors. J Neurooncol. 1995;26:165–70. [DOI] [PubMed]
Garzia L, Kijima N, Morrissy AS, Antonellis PD, Guerreiro-Stucklin A, Holgado BL, et al. A hematogenous route for medulloblastoma leptomeningeal metastases. Cell. 2018;172:1050-1062.e14. [DOI] [PubMed] [PMC]
Eibl RH.From leukocyte trafficking to tumor cell metastasis - a new approach for the development of antimetastatic drugs. Biochem Soc Trans. 2000;28:A350. [DOI]
Eibl RH.Rapid arrest of metastasizing melanoma cells under flow conditions. Virchows Arch. 2001;439:241–2.
Eibl RH, Kremer M, Herzog C, Kitsanta E, Fend F, Schlegel J, et al. Role of metastasis-associated chemokine receptors in breast and brain tumors. Acta Neuropathol (Berl). 2001;102:532.
Eibl RH, Höfler H.The multistep homing model of tumor metastasis: from inflammatory cell adhesion molecules to chemokine receptors. Inflamm Res. 2001;50:201.
Eibl RH, Höfler H.The multistep homing model of tumor metastasis: from cell adhesion molecules to chemokine receptors. Scand J Immunol. 2001;54:50.
Eibl RH, Moy VT.AFM-based adhesion measurements of single receptor-ligand bonds on living cells. In: Pandalai SG, editor. Recent research developments in biophysics. Trivandrum: Transworld Research Network; 2004. pp. 235–46.
Eibl RH, Moy VT.Atomic Force Microscopy Measurements of Protein-Ligand Interactions on Living Cells. In: Ulrich Nienhaus G, editor. Protein-Ligand interactions: methods and applications. Totowa, NJ: Humana Press; 2005. pp. 439–49. [DOI] [PubMed]
Eibl RH.First measurement of physiologic VLA-4 activation by SDF-1 at the single-molecule level on a living cell. In: Hinterdorfer P, Schütz G, Pohl P, editor. Proceedings of the VIII Linz winter workshop: advances in single molecule research for biology and nanoscience. Linz: Trauner; 2006. pp. 40–3.
Eibl RH.Direct Force Measurements of Receptor–Ligand Interactions on Living Cells. In: Bhushan B, Fuchs H, editor. Applied scanning probe methods XII: characterization. Berlin, Heidelberg: Springer; 2009. pp. 1–31. [DOI]
Eibl RH.Cell Adhesion Receptors Studied by AFM-Based Single-Molecule Force Spectroscopy. In: Bhushan B, editor. Scanning probe microscopy in nanoscience and nanotechnology 2. Berlin, Heidelberg: Springer; 2011. pp. 197–215. [DOI]
Eibl RH.Single-Molecule Studies of Integrins by AFM-Based Force Spectroscopy on Living Cells. In: Bhushan B, editor. Scanning probe microscopy in nanoscience and nanotechnology 3. Berlin, Heidelberg: Springer; 2013. pp. 137–69. [DOI]
Eibl RH.Comment on “A method to measure cellular adhesion utilizing a polymer micro-cantilever” [Appl. Phys. Lett. 103, 123702 (2013)]. Appl Phys Lett. 2014;104:236103. [DOI] [PubMed] [PMC]
Eibl RH.Atomic force microscopy measurement of SDF-1 mediated affinity modulation of single VLA-4 - VCAM-1 bonds. In: Skamene E, editor. Immunology2004. Bologna, Italy: Medimond; 2004. pp. 115–20.
Chen WW, Balaj L, Liau LM, Samuels ML, Kotsopoulos SK, Maguire CA, et al. BEAMing and droplet digital PCR analysis of mutant IDH1 mRNA in glioma patient serum and cerebrospinal fluid extracellular vesicles. Mol Ther Nucleic Acids. 2013;2:e109. [DOI] [PubMed] [PMC]
Floyd D, Purow B.Micro-masters of glioblastoma biology and therapy: increasingly recognized roles for microRNAs. Neuro Oncol. 2014;16:622–7. [DOI] [PubMed] [PMC]
Kitano Y, Aoki K, Ohka F, Yamazaki S, Motomura K, Tanahashi K, et al. Urinary MicroRNA-based diagnostic model for central nervous system tumors using nanowire scaffolds. ACS Appl Mater Interfaces. 2021;13:17316–29. [DOI] [PubMed]
Gonzalez-Beltran AN, Masuzzo P, Ampe C, Bakker GJ, Besson S, Eibl RH, et al. Community standards for open cell migration data. Gigascience. 2020;9:giaa041. [DOI] [PubMed] [PMC]
Pembrolizumab and a vaccine (ATL-DC) for the treatment of surgically accessible recurrent glioblastoma [Internet]. Bethesda (MD): U.S. National Library of Medicine; [cited 2023 Jan 11]. Available from: https://clinicaltrials.gov/ct2/show/NCT04201873
Tessa Jowell BRAIN MATRIX - platform study (BRAIN MATRIX) [Internet]. Bethesda (MD): U.S. National Library of Medicine; [cited 2023 Jan 11]. Available from: https://clinicaltrials.gov/ct2/show/NCT04274283
The circTeloDIAG: a new approach of liquid biopsy for the diagnosis and follow-up of patients with glioma tumor [Internet]. Bethesda (MD): U.S. National Library of Medicine; [cited 2023 Jan 11]. Available from: https://clinicaltrials.gov/ct2/show/NCT04931732
Profiling program of cancer patients with sequential tumor and liquid biopsies (PLANET) [Internet]. Bethesda (MD): U.S. National Library of Medicine; [cited 2023 Jan 11]. Available from: https://clinicaltrials.gov/ct2/show/NCT05099068
Pagès M, Rotem D, Gydush G, Reed S, Rhoades J, Ha G, et al. Liquid biopsy detection of genomic alterations in pediatric brain tumors from cell-free DNA in peripheral blood, CSF, and urine. Neuro Oncol. 2022;24:1352–63. [DOI] [PubMed] [PMC]
Glioma brain tumours - E12513 - sensiscreen glioma [Internet]. Bethesda (MD): U.S. National Library of Medicine; [cited 2023 Jan 11]. Available from: https://clinicaltrials.gov/ct2/show/NCT04539431
Blood-brain barrier disruption (BBBD) for liquid biopsy in subjects with glioblastoma brain tumor [Internet]. Bethesda (MD): U.S. National Library of Medicine; [cited 2023 Jan 11]. Available from: https://clinicaltrials.gov/ct2/show/NCT05383872
Liquid biopsy in low-grade glioma patients (GLIOLIPSY) [Internet]. Bethesda (MD): U.S. National Library of Medicine; [cited 2023 Jan 11]. Available from: https://clinicaltrials.gov/ct2/show/NCT05133154
Combing a deep learning-based radiomics with liquid biopsy for preoperative and non-invasive diagnosis of glioma [Internet]. Bethesda (MD): U.S. National Library of Medicine; [cited 2023 Jan 11]. Available from: https://clinicaltrials.gov/ct2/show/NCT05536024
Carvedilol with chemotherapy in second line glioblastoma and response of circulating tumor cells [Internet]. Bethesda (MD): U.S. National Library of Medicine; [cited 2023 Jan 11]. Available from: https://clinicaltrials.gov/ct2/show/NCT03861598
Anti-cancer effects of carvedilol with standard treatment in glioblastoma and response of peripheral glioma circulating tumor cells [Internet]. Bethesda (MD): U.S. National Library of Medicine; [cited 2023 Jan 11]. Available from: https://clinicaltrials.gov/ct2/show/NCT03980249
Multimodality MRI and liquid biopsy in GBM [Internet]. Bethesda (MD): U.S. National Library of Medicine; [cited 2023 Jan 11]. Available from: https://clinicaltrials.gov/ct2/show/NCT04776980
Evaluation of circulating tumor DNA as a theranostic marker in the management of glioblastomas (Bi- GLAM) [Internet]. Bethesda (MD): U.S. National Library of Medicine; [cited 2023 Jan 11]. Available from: https://clinicaltrials.gov/ct2/show/NCT03115138
Detecting malignant brain tumor cells in the bloodstream during surgery to remove the tumor [Internet]. Bethesda (MD): U.S. National Library of Medicine; [cited 2023 Jan 11]. Available from: https://clinicaltrials.gov/ct2/show/record/NCT00001148
Laboratory study of early tumor markers in the peripheral blood of glioblastoma multiforme patients [Internet]. Bethesda (MD): U.S. National Library of Medicine; [cited 2023 Jan 11]. Available from: https://clinicaltrials.gov/ct2/show/NCT01135875
Sonobiopsy for noninvasive and sensitive detection of glioblastoma [Internet]. Bethesda (MD): U.S. National Library of Medicine; [cited 2023 Jan 11]. Available from: https://clinicaltrials.gov/ct2/show/NCT05281731
Ohgaki H, Eibl RH, Wiestler OD, Yasargil MG, Newcomb EW, Kleihues P.p53 mutations in nonastrocytic human brain tumors. Cancer Res. 1991;51:6202–5. [PubMed]