Glioma through the looking GLASS: molecular evolution of diffuse gliomas and the Glioma Longitudinal Analysis Consortium

GLASS Consortium, Kenneth Aldape, Samirkumar B Amin, David M Ashley, Jill S Barnholtz-Sloan, Amanda J Bates, Rameen Beroukhim, Christoph Bock, Daniel J Brat, Elizabeth B Claus, Joseph F Costello, John F de Groot, Gaetano Finocchiaro, Pim J French, Hui K Gan, Brent Griffith, Christel C Herold-Mende, Craig Horbinski, Antonio Iavarone, Steven N Kalkanis, Konstantina Karabatsou, Hoon Kim, Mathilde C M Kouwenhoven, Kerrie L McDonald, Hrvoje Miletic, Do-Hyun Nam, Ho Keung Ng, Simone P Niclou, Houtan Noushmehr, D Ryan Ormond, Laila M Poisson, Guido Reifenberger, Federico Roncaroli, Jason K Sa, Peter A E Sillevis Smitt, Marion Smits, Camila F Souza, Ghazaleh Tabatabai, Erwin G Van Meir, Roel G W Verhaak, Colin Watts, Pieter Wesseling, Adelheid Woehrer, W K Alfred Yung, Christine Jungk, Ann-Christin Hau, Eric van Dyck, Bart A Westerman, Julia Yin, Olajide Abiola, Nikolaj Zeps, Sean Grimmond, Michael Buckland, Mustafa Khasraw, Erik P Sulman, Andrea M Muscat, Lucy Stead, GLASS Consortium, Kenneth Aldape, Samirkumar B Amin, David M Ashley, Jill S Barnholtz-Sloan, Amanda J Bates, Rameen Beroukhim, Christoph Bock, Daniel J Brat, Elizabeth B Claus, Joseph F Costello, John F de Groot, Gaetano Finocchiaro, Pim J French, Hui K Gan, Brent Griffith, Christel C Herold-Mende, Craig Horbinski, Antonio Iavarone, Steven N Kalkanis, Konstantina Karabatsou, Hoon Kim, Mathilde C M Kouwenhoven, Kerrie L McDonald, Hrvoje Miletic, Do-Hyun Nam, Ho Keung Ng, Simone P Niclou, Houtan Noushmehr, D Ryan Ormond, Laila M Poisson, Guido Reifenberger, Federico Roncaroli, Jason K Sa, Peter A E Sillevis Smitt, Marion Smits, Camila F Souza, Ghazaleh Tabatabai, Erwin G Van Meir, Roel G W Verhaak, Colin Watts, Pieter Wesseling, Adelheid Woehrer, W K Alfred Yung, Christine Jungk, Ann-Christin Hau, Eric van Dyck, Bart A Westerman, Julia Yin, Olajide Abiola, Nikolaj Zeps, Sean Grimmond, Michael Buckland, Mustafa Khasraw, Erik P Sulman, Andrea M Muscat, Lucy Stead

Abstract

Adult diffuse gliomas are a diverse group of brain neoplasms that inflict a high emotional toll on patients and their families. The Cancer Genome Atlas and similar projects have provided a comprehensive understanding of the somatic alterations and molecular subtypes of glioma at diagnosis. However, gliomas undergo significant cellular and molecular evolution during disease progression. We review the current knowledge on the genomic and epigenetic abnormalities in primary tumors and after disease recurrence, highlight the gaps in the literature, and elaborate on the need for a new multi-institutional effort to bridge these knowledge gaps and how the Glioma Longitudinal Analysis Consortium (GLASS) aims to systemically catalog the longitudinal changes in gliomas. The GLASS initiative will provide essential insights into the evolution of glioma toward a lethal phenotype, with the potential to reveal targetable vulnerabilities and, ultimately, improved outcomes for a patient population in need.

Figures

Fig. 1
Fig. 1
Usual course of glioma management. GLASS would improve the assessment of gliomas, particularly the prediction of malignant transformation, treatment monitoring, and assessment of tumor alterations noninvasively with imaging and/or liquid biopsies. SMDT (tumor board): specialist multidisciplinary team; RT: radiotherapy.
Fig. 2
Fig. 2
Simplified glioma evolution models. The glioma-initiating cell evolves into the tumor at diagnosis with selective pressures resulting in intratumoral heterogeneity. Recurrent tumors share few or the majority of the somatic alterations seen in the diagnostic tumors depending on the evolutionary pattern (linear, branching, or ancestral evolutions). Subclones may be marked by mutations or extrachromosomal DNA elements.

References

    1. Ostrom QT, Gittleman H, Xu J, et al. . CBTRUS Statistical Report: primary brain and other central nervous system tumors diagnosed in the United States in 2009-2013. Neuro Oncol. 2016;18(suppl 5):v1–v75.
    1. Khasraw M, Lassman AB. Advances in the treatment of malignant gliomas. Curr Oncol Rep. 2010;12(1):26–33.
    1. Khasraw M, Ameratunga MS, Grant R, Wheeler H, Pavlakis N. Antiangiogenic therapy for high-grade glioma. Cochrane Database Syst Rev. 2014;(9):CD008218. PMID: 25242542.
    1. Van Meir EG, Hadjipanayis CG, Norden AD, Shu HK, Wen PY, Olson JJ. Exciting new advances in neuro-oncology: the avenue to a cure for malignant glioma. CA Cancer J Clin. 2010;60(3):166–193.
    1. Stupp R, Mason WP, van den Bent MJ, et al. ; European Organisation for Research and Treatment of Cancer Brain Tumor and Radiotherapy Groups; National Cancer Institute of Canada Clinical Trials Group Radiotherapy plus concomitant and adjuvant temozolomide for glioblastoma. N Engl J Med. 2005;352(10):987–996.
    1. Wen PY, Macdonald DR, Reardon DA, et al. . Updated response assessment criteria for high-grade gliomas: response assessment in neuro-oncology working group. J Clin Oncol. 2010;28(11):1963–1972.
    1. Brennan CW, Verhaak RG, McKenna A, et al. ; TCGA Research Network The somatic genomic landscape of glioblastoma. Cell. 2013;155(2):462–477.
    1. Cancer Genome Atlas Research Network. Comprehensive genomic characterization defines human glioblastoma genes and core pathways. Nature 2008;455:1061–1068.
    1. Ceccarelli M, Barthel FP, Malta TM, et al. ; TCGA Research Network Molecular profiling reveals biologically discrete subsets and pathways of progression in diffuse glioma. Cell. 2016;164(3):550–563.
    1. Noushmehr H, Weisenberger DJ, Diefes K, et al. ; Cancer Genome Atlas Research Network Identification of a CpG island methylator phenotype that defines a distinct subgroup of glioma. Cancer Cell. 2010;17(5):510–522.
    1. Brat DJ, Verhaak RG, Aldape KD, et al. ; Cancer Genome Atlas Research Network Comprehensive, integrative genomic analysis of diffuse lower-grade gliomas. N Engl J Med. 2015;372(26):2481–2498.
    1. Verhaak RG, Hoadley KA, Purdom E, et al. ; Cancer Genome Atlas Research Network 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.
    1. Bettegowda C, Agrawal N, Jiao Y, et al. . Mutations in CIC and FUBP1 contribute to human oligodendroglioma. Science. 2011;333(6048):1453–1455.
    1. Gravendeel LA, Kouwenhoven MC, Gevaert O, et al. . Intrinsic gene expression profiles of gliomas are a better predictor of survival than histology. Cancer Res. 2009;69(23):9065–9072.
    1. Phillips HS, Kharbanda S, Chen R, et al. . 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.
    1. Sturm D, Witt H, Hovestadt V, et al. . Hotspot mutations in H3F3A and IDH1 define distinct epigenetic and biological subgroups of glioblastoma. Cancer Cell. 2012;22(4):425–437.
    1. Suzuki H, Aoki K, Chiba K, et al. . Mutational landscape and clonal architecture in grade II and III gliomas. Nat Genet. 2015;47(5):458–468.
    1. Yan H, Parsons DW, Jin G, et al. . IDH1 and IDH2 mutations in gliomas. N Engl J Med. 2009;360(8):765–773.
    1. Louis DN, Perry A, Reifenberger G, et al. . The 2016 World Health Organization classification of tumors of the central nervous system: a summary. Acta Neuropathol. 2016;131(6):803–820.
    1. Eskilsson E, Verhaak RG. Longitudinal genomic characterization of brain tumors for identification of therapeutic vulnerabilities. Neuro Oncol. 2016;18(8):1037–1039.
    1. Blank CU, Haanen JB, Ribas A, Schumacher TN. CANCER IMMUNOLOGY. The “cancer immunogram”. Science. 2016;352(6286):658–660.
    1. Osuka S, Van Meir EG. Overcoming therapeutic resistance in glioblastoma: the way forward. J Clin Invest. 2017;127(2):415–426.
    1. Perry A, Wesseling P. Histologic classification of gliomas. Handb Clin Neurol. 2016;134:71–95.
    1. Eckel-Passow JE, Lachance DH, Molinaro AM, et al. . Glioma groups based on 1p/19q, IDH, and TERT promoter mutations in tumors. N Engl J Med. 2015;372(26):2499–2508.
    1. Louis DN, Perry A, Burger P, et al. ; International Society of Neuropathology–Haarlem International Society of Neuropathology–Haarlem consensus guidelines for nervous system tumor classification and grading. Brain Pathol. 2014;24(5):429–435.
    1. Dubbink HJ, Atmodimedjo PN, Kros JM, et al. . Molecular classification of anaplastic oligodendroglioma using next-generation sequencing: a report of the prospective randomized EORTC Brain Tumor Group 26951 phase III trial. Neuro Oncol. 2016;18(3):388–400.
    1. Yan W, Zhang W, You G, et al. . Molecular classification of gliomas based on whole genome gene expression: a systematic report of 225 samples from the Chinese Glioma Cooperative Group. Neuro Oncol. 2012;14(12):1432–1440.
    1. Jiao Y, Killela PJ, Reitman ZJ, et al. . Frequent ATRX, CIC, FUBP1 and IDH1 mutations refine the classification of malignant gliomas. Oncotarget. 2012;3(7):709–722.
    1. Wiestler B, Capper D, Sill M, et al. . Integrated DNA methylation and copy-number profiling identify three clinically and biologically relevant groups of anaplastic glioma. Acta Neuropathol. 2014;128(4):561–571.
    1. Olar A, Wani KM, Alfaro-Munoz KD, et al. . IDH mutation status and role of WHO grade and mitotic index in overall survival in grade II-III diffuse gliomas. Acta Neuropathol. 2015;129(4):585–596.
    1. Reuss DE, Sahm F, Schrimpf D, et al. . ATRX and IDH1-R132H immunohistochemistry with subsequent copy number analysis and IDH sequencing as a basis for an “integrated” diagnostic approach for adult astrocytoma, oligodendroglioma and glioblastoma. Acta Neuropathol. 2015;129(1):133–146.
    1. Weller M, Cloughesy T, Perry JR, Wick W. Standards of care for treatment of recurrent glioblastoma—are we there yet?Neuro Oncol. 2013;15(1):4–27.
    1. Barthel FP, Wesseling P, Verhaak RGW. Reconstructing the molecular life history of gliomas. Acta Neuropathol. 2018;135(5):649–670. PMID:29616301.
    1. Kim H, Zheng S, Amini SS, et al. . Whole-genome and multisector exome sequencing of primary and post-treatment glioblastoma reveals patterns of tumor evolution. Genome Res. 2015;25(3):316–327.
    1. Sottoriva A, Spiteri I, Piccirillo SG, et al. . Intratumor heterogeneity in human glioblastoma reflects cancer evolutionary dynamics. Proc Natl Acad Sci U S A 2013;110:4009–4014.
    1. Johnson BE, Mazor T, Hong C, et al. . Mutational analysis reveals the origin and therapy-driven evolution of recurrent glioma. Science. 2014;343(6167):189–193.
    1. Navin N, Kendall J, Troge J, et al. . Tumour evolution inferred by single-cell sequencing. Nature. 2011;472(7341):90–94.
    1. Driessens G, Beck B, Caauwe A, Simons BD, Blanpain C. Defining the mode of tumour growth by clonal analysis. Nature. 2012;488(7412):527–530.
    1. Bedard PL, Hansen AR, Ratain MJ, Siu LL. Tumour heterogeneity in the clinic. Nature. 2013;501(7467):355–364.
    1. Snuderl M, Fazlollahi L, Le LP, et al. . Mosaic amplification of multiple receptor tyrosine kinase genes in glioblastoma. Cancer Cell. 2011;20(6):810–817.
    1. Szerlip NJ, Pedraza A, Chakravarty D, et al. . Intratumoral heterogeneity of receptor tyrosine kinases EGFR and PDGFRA amplification in glioblastoma defines subpopulations with distinct growth factor response. Proc Natl Acad Sci U S A 2012;109:3041–3046.
    1. Francis JM, Zhang CZ, Maire CL, et al. . EGFR variant heterogeneity in glioblastoma resolved through single-nucleus sequencing. Cancer Discov. 2014;4(8):956–971.
    1. Mazor T, Pankov A, Johnson BE, et al. . DNA methylation and somatic mutations converge on the cell cycle and define similar evolutionary histories in brain tumors. Cancer Cell. 2015;28(3):307–317.
    1. Bai H, Harmancı AS, Erson-Omay EZ, et al. . Integrated genomic characterization of IDH1-mutant glioma malignant progression. Nat Genet. 2016;48(1):59–66.
    1. Kumar A, Boyle EA, Tokita M, et al. . Deep sequencing of multiple regions of glial tumors reveals spatial heterogeneity for mutations in clinically relevant genes. Genome Biol. 2014;15(12):530.
    1. Aubry M, de Tayrac M, Etcheverry A, et al. . From the core to beyond the margin: a genomic picture of glioblastoma intratumor heterogeneity. Oncotarget. 2015;6(14):12094–12109.
    1. Lee JK, Wang J, Sa JK, et al. . Spatiotemporal genomic architecture informs precision oncology in glioblastoma. Nat Genet. 2017;49(4):594–599. PMID: 28263318.
    1. deCarvalho AC, Kim H, Poisson LM, et al. . Discordant inheritance of chromosomal and extrachromosomal DNA elements contributes to dynamic disease evolution in glioblastoma. Nat Genet. 2018;50(5):708–717. PMID: 29686388.
    1. Nathanson DA, Gini B, Mottahedeh J, et al. . Targeted therapy resistance mediated by dynamic regulation of extrachromosomal mutant EGFR DNA. Science. 2014;343(6166):72–76.
    1. Turner KM, Deshpande V, Beyter D, et al. . Extrachromosomal oncogene amplification drives tumour evolution and genetic heterogeneity. Nature. 2017;543(7643):122–125. PMID: 28178237.
    1. Nikolaev S, Santoni F, Garieri M, et al. . Extrachromosomal driver mutations in glioblastoma and low-grade glioma. Nat Commun. 2014;5:5690.
    1. Vogt N, Lefevre SH, Apiou F, et al. . Molecular structure of double-minute chromosomes bearing amplified copies of the epidermal growth factor receptor gene in gliomas. Proc Natl Acad Sci U S A 2004;101:11368–11373.
    1. Zheng S, Fu J, Vegesna R, et al. . A survey of intragenic breakpoints in glioblastoma identifies a distinct subset associated with poor survival. Genes Dev. 2013;27(13):1462–1472.
    1. Abou-El-Ardat K, Seifert M, Becker K, et al. . Comprehensive molecular characterization of multifocal glioblastoma proves its monoclonal origin and reveals novel insights into clonal evolution and heterogeneity of glioblastomas. Neuro Oncol 2017;19:546–557.
    1. Liu Q, Liu Y, Li W, et al. . Genetic, epigenetic, and molecular landscapes of multifocal and multicentric glioblastoma. Acta Neuropathol. 2015;130(4):587–597.
    1. Raiber EA, Beraldi D, Martínez Cuesta S, et al. . Base resolution maps reveal the importance of 5-hydroxymethylcytosine in a human glioblastoma. NPJ Genom Med. 2017;2:6.
    1. Johnson KC, Houseman EA, King JE, von Herrmann KM, Fadul CE, Christensen BC. 5-Hydroxymethylcytosine localizes to enhancer elements and is associated with survival in glioblastoma patients. Nat Commun. 2016;7:13177.
    1. Engler JR, Robinson AE, Smirnov I, et al. . Increased microglia/macrophage gene expression in a subset of adult and pediatric astrocytomas. PLoS One. 2012;7(8):e43339.
    1. Wang Q, Hu B, Hu X, et al. . Tumor evolution of glioma-intrinsic gene expression subtypes associates with immunological changes in the microenvironment. Cancer Cell. 2017;32(1):42–56.e6.
    1. Müller S, Liu SJ, Di Lullo E, et al. . Single-cell sequencing maps gene expression to mutational phylogenies in PDGF- and EGF-driven gliomas. Mol Syst Biol. 2016;12(11):889.
    1. Patel AP, Tirosh I, Trombetta JJ, et al. . Single-cell RNA-seq highlights intratumoral heterogeneity in primary glioblastoma. Science. 2014;344(6190):1396–1401.
    1. Tirosh I, Venteicher AS, Hebert C, et al. . Single-cell RNA-seq supports a developmental hierarchy in human oligodendroglioma. Nature. 2016;539(7628):309–313.
    1. Venteicher AS, Tirosh I, Hebert C, et al. . Decoupling genetics, lineages, and microenvironment in IDH-mutant gliomas by single-cell RNA-seq. Science 2017;355:doi: 10.1126/science.aai8478.
    1. Hunter C, Smith R, Cahill DP, et al. . A hypermutation phenotype and somatic MSH6 mutations in recurrent human malignant gliomas after alkylator chemotherapy. Cancer Res. 2006;66(8):3987–3991.
    1. Bouffet E, Larouche V, Campbell BB, et al. . Immune checkpoint inhibition for hypermutant glioblastoma multiforme resulting from germline biallelic mismatch repair deficiency. J Clin Oncol. 2016;34(19):2206–2211.
    1. Jue TR, Nozue K, Lester AJ, et al. . Veliparib in combination with radiotherapy for the treatment of MGMT unmethylated glioblastoma. J Transl Med. 2017;15(1):61.
    1. Yip S, Miao J, Cahill DP, et al. . MSH6 mutations arise in glioblastomas during temozolomide therapy and mediate temozolomide resistance. Clin Cancer Res. 2009;15(14):4622–4629.
    1. Kim J, Lee IH, Cho HJ, et al. . Spatiotemporal evolution of the primary glioblastoma genome. Cancer Cell. 2015;28(3):318–328.
    1. Wang J, Cazzato E, Ladewig E, et al. . Clonal evolution of glioblastoma under therapy. Nat Genet. 2016;48(7):768–776.
    1. Erson-Omay EZ, Henegariu O, Omay SB, et al. . Longitudinal analysis of treatment-induced genomic alterations in gliomas. Genome Med. 2017;9(1):12.
    1. van den Bent MJ, Gao Y, Kerkhof M, et al. . Changes in the EGFR amplification and EGFRvIII expression between paired primary and recurrent glioblastomas. Neuro Oncol. 2015;17(7):935–941.
    1. Nutt CL, Mani DR, Betensky RA, et al. . Gene expression-based classification of malignant gliomas correlates better with survival than histological classification. Cancer Res. 2003;63(7):1602–1607.
    1. Kwon SM, Kang SH, Park CK, et al. . Recurrent glioblastomas reveal molecular subtypes associated with mechanistic implications of drug-resistance. PLoS One. 2015;10(10):e0140528.
    1. Bhat KPL, Balasubramaniyan V, Vaillant B, et al. . Mesenchymal differentiation mediated by NF-κB promotes radiation resistance in glioblastoma. Cancer Cell. 2013;24(3):331–346.
    1. Flavahan WA, Drier Y, Liau BB, et al. . Insulator dysfunction and oncogene activation in IDH mutant gliomas. Nature. 2016;529(7584):110–114.
    1. Lu C, Ward PS, Kapoor GS, et al. . IDH mutation impairs histone demethylation and results in a block to cell differentiation. Nature. 2012;483(7390):474–478.
    1. Kohanbash G, Carrera DA, Shrivastav S, et al. . Isocitrate dehydrogenase mutations suppress STAT1 and CD8+ T cell accumulation in gliomas. J Clin Invest. 2017;127(4):1425–1437.
    1. de Souza CF, Sabedot TS, Malta TM, et al. . A distinct DNA methylation shift in a subset of glioma CpG island methylator phenotypes during tumor recurrence. Cell Rep. 2018;23(2):637–651. PMID: 29642018.
    1. Klughammer J, Kiesel B, Roetzer T, et al. . The DNA methylation landscape of glioblastoma disease progression shows extensive heterogeneity in time and space. bioRxiv 2017.
    1. Ellingson BM, Bendszus M, Boxerman J, et al. ; Jumpstarting Brain Tumor Drug Development Coalition Imaging Standardization Steering Committee Consensus recommendations for a standardized Brain Tumor Imaging Protocol in clinical trials. Neuro Oncol. 2015;17(9):1188–1198.
    1. Law M, Yang S, Wang H, et al. . Glioma grading: sensitivity, specificity, and predictive values of perfusion MR imaging and proton MR spectroscopic imaging compared with conventional MR imaging. AJNR Am J Neuroradiol. 2003;24(10):1989–1998.
    1. Albert NL, Weller M, Suchorska B, et al. . Response Assessment in Neuro-Oncology working group and European Association for Neuro-Oncology recommendations for the clinical use of PET imaging in gliomas. Neuro Oncol. 2016;18(9):1199–1208.
    1. Jamshidi N, Diehn M, Bredel M, Kuo MD. Illuminating radiogenomic characteristics of glioblastoma multiforme through integration of MR imaging, messenger RNA expression, and DNA copy number variation. Radiology. 2014;270(1):1–2.
    1. Gevaert O, Mitchell LA, Achrol AS, et al. . Glioblastoma multiforme: exploratory radiogenomic analysis by using quantitative image features. Radiology. 2014;273(1):168–174.
    1. Kalinina J, Carroll A, Wang L, et al. . Detection of “oncometabolite” 2-hydroxyglutarate by magnetic resonance analysis as a biomarker of IDH1/2 mutations in glioma. J Mol Med (Berl). 2012;90(10):1161–1171.
    1. Kloosterhof NK, Bralten LB, Dubbink HJ, French PJ, van den Bent MJ. Isocitrate dehydrogenase-1 mutations: a fundamentally new understanding of diffuse glioma?Lancet Oncol. 2011;12(1):83–91.
    1. Van Meter T, Dumur C, Hafez N, Garrett C, Fillmore H, Broaddus WC. Microarray analysis of MRI-defined tissue samples in glioblastoma reveals differences in regional expression of therapeutic targets. Diagn Mol Pathol. 2006;15(4):195–205.
    1. Melin BS, Barnholtz-Sloan JS, Wrensch MR, et al. ; GliomaScan Consortium Genome-wide association study of glioma subtypes identifies specific differences in genetic susceptibility to glioblastoma and non-glioblastoma tumors. Nat Genet. 2017;49(5):789–794.
    1. Wrensch M, Jenkins RB, Chang JS, et al. . Variants in the CDKN2B and RTEL1 regions are associated with high-grade glioma susceptibility. Nat Genet. 2009;41(8):905–908.
    1. Hudson TJ, Anderson W, Artez A, et al. ; International Cancer Genome Consortium International network of cancer genome projects. Nature. 2010;464(7291):993–998.
    1. Downing JR, Wilson RK, Zhang J, et al. . The Pediatric Cancer Genome Project. Nat Genet. 2012;44(6):619–622.
    1. Esteve-Codina A, Arpi O, Martinez-García M, et al. ; GLIOCAT Group A comparison of RNA-Seq results from paired formalin-fixed paraffin-embedded and fresh-frozen glioblastoma tissue samples. PLoS One. 2017;12(1):e0170632.
    1. Erdem-Eraslan L, van den Bent MJ, Hoogstrate Y, et al. . Identification of patients with recurrent glioblastoma who may benefit from combined bevacizumab and CCNU therapy: a report from the BELOB trial. Cancer Res. 2016;76(3):525–534.

Source: PubMed

Sponsors and Collaborators

Medical Conditions

Drug Interventions

3
Subscribe