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

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.

[1]  Martin Sill,et al.  Integrated DNA methylation and copy-number profiling identify three clinically and biologically relevant groups of anaplastic glioma , 2014, Acta Neuropathologica.

[2]  M. Berger,et al.  Increased Microglia/Macrophage Gene Expression in a Subset of Adult and Pediatric Astrocytomas , 2012, PloS one.

[3]  Alexander R. Pico,et al.  Variants in the CDKN2B and RTEL1 regions are associated with high grade glioma susceptibility , 2009, Nature Genetics.

[4]  Li Ding,et al.  The Pediatric Cancer Genome Project , 2012, Nature Genetics.

[5]  P. Loehrer.  Radiotherapy Plus Concomitant and Adjuvant Temozolomide for Glioblastoma , 2006 .

[6]  Alex A. Pollen,et al.  Single‐cell sequencing maps gene expression to mutational phylogenies in PDGF‐ and EGF‐driven gliomas , 2016, Molecular Systems Biology.

[7]  S. Antonarakis,et al.  Extrachromosomal driver mutations in glioblastoma and low grade glioma , 2014, Nature Communications.

[8]  Neema Jamshidi,et al.  Illuminating radiogenomic characteristics of glioblastoma multiforme through integration of MR imaging, messenger RNA expression, and DNA copy number variation. , 2013, Radiology.

[9]  S. Gabriel,et al.  Integrated genomic analysis identifies clinically relevant subtypes of glioblastoma characterized by abnormalities in PDGFRA, IDH1, EGFR, and NF1. , 2010, Cancer cell.

[10]  Alexander R. Pico,et al.  Glioma Groups Based on 1p/19q, IDH, and TERT Promoter Mutations in Tumors. , 2015, The New England journal of medicine.

[11]  In-Hee Lee,et al.  Clonal evolution of glioblastoma under therapy , 2016, Nature Genetics.

[12]  F. Ducray,et al.  IDH1 and IDH2 mutations in gliomas. , 2009, The New England journal of medicine.

[13]  David T. W. Jones,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 , 2014, Acta Neuropathologica.

[14]  Michael Weller,et al.  Standards of care for treatment of recurrent glioblastoma--are we there yet? , 2013, Neuro-oncology.

[15]  Mariella G. Filbin,et al.  Single-cell RNA-seq supports a developmental hierarchy in human oligodendroglioma , 2016, Nature.

[16]  Glyn Johnson,et al.  Glioma grading: sensitivity, specificity, and predictive values of perfusion MR imaging and proton MR spectroscopic imaging compared with conventional MR imaging. , 2003, AJNR. American journal of neuroradiology.

[17]  V. P. Collins,et al.  Intratumor heterogeneity in human glioblastoma reflects cancer evolutionary dynamics , 2013, Proceedings of the National Academy of Sciences.

[18]  K. Aldape,et al.  IDH mutation status and role of WHO grade and mitotic index in overall survival in grade II–III diffuse gliomas , 2015, Acta Neuropathologica.

[19]  G. Reifenberger,et al.  The 2016 World Health Organization Classification of Tumors of the Central Nervous System: a summary , 2016, Acta Neuropathologica.

[20]  J. Costello,et al.  Isocitrate dehydrogenase mutations suppress STAT1 and CD8+ T cell accumulation in gliomas , 2017, The Journal of clinical investigation.

[21]  Erwin G. Van Meir,et al.  Detection of “oncometabolite” 2-hydroxyglutarate by magnetic resonance analysis as a biomarker of IDH1/2 mutations in glioma , 2012, Journal of Molecular Medicine.

[22]  S. Nelson,et al.  Targeted Therapy Resistance Mediated by Dynamic Regulation of Extrachromosomal Mutant EGFR DNA , 2014, Science.

[23]  Pieter Wesseling,et al.  Histologic classification of gliomas. , 2016, Handbook of clinical neurology.

[24]  M. J. van den Bent,et al.  Isocitrate dehydrogenase-1 mutations: a fundamentally new understanding of diffuse glioma? , 2011, The Lancet. Oncology.

[25]  J. Mosser,et al.  ‘From the core to beyond the margin’: a genomic picture of glioblastoma intratumor heterogeneity , 2014, Oncotarget.

[26]  Helen Wheeler,et al.  Antiangiogenic therapy for high-grade glioma. , 2014, The Cochrane database of systematic reviews.

[27]  Susan M. Chang,et al.  Updated response assessment criteria for high-grade gliomas: response assessment in neuro-oncology working group. , 2010, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[28]  Joshua M. Korn,et al.  Comprehensive genomic characterization defines human glioblastoma genes and core pathways , 2008, Nature.

[29]  Emanuel F Petricoin,et al.  Discordant inheritance of chromosomal and extrachromosomal DNA elements contributes to dynamic disease evolution in glioblastoma , 2018, Nature Genetics.

[30]  D. Merico,et al.  Immune Checkpoint Inhibition for Hypermutant Glioblastoma Multiforme Resulting From Germline Biallelic Mismatch Repair Deficiency. , 2016, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[31]  S. Plevritis,et al.  Glioblastoma multiforme: exploratory radiogenomic analysis by using quantitative image features. , 2014, Radiology.

[32]  J. Barnholtz-Sloan,et al.  CBTRUS Statistical Report: Primary Brain and Other Central Nervous System Tumors Diagnosed in the United States in 2009-2013. , 2016, Neuro-oncology.

[33]  Antoni Ribas,et al.  The “cancer immunogram” , 2016, Science.

[34]  Jessica M. Rusert,et al.  Extrachromosomal oncogene amplification drives tumor evolution and genetic heterogeneity , 2017, Nature.

[35]  Marion Smits,et al.  Consensus recommendations for a standardized Brain Tumor Imaging Protocol in clinical trials. , 2015, Neuro-oncology.

[36]  Ken Chen,et al.  A survey of intragenic breakpoints in glioblastoma identifies a distinct subset associated with poor survival. , 2013, Genes & development.

[37]  M. Khasraw,et al.  Veliparib in combination with radiotherapy for the treatment of MGMT unmethylated glioblastoma , 2017, Journal of Translational Medicine.

[38]  Mark J. Ratain,et al.  Tumour heterogeneity in the clinic , 2013, Nature.

[39]  T. Golub,et al.  Gene expression-based classification of malignant gliomas correlates better with survival than histological classification. , 2003, Cancer research.

[40]  R. Wilson,et al.  Identification of a CpG island methylator phenotype that defines a distinct subgroup of glioma. , 2010, Cancer cell.

[41]  Andrew P. Stubbs,et al.  Intrinsic gene expression profiles of gliomas are a better predictor of survival than histology. , 2009, Cancer research.

[42]  R. Verhaak,et al.  Longitudinal genomic characterization of brain tumors for identification of therapeutic vulnerabilities. , 2016, Neuro-oncology.

[43]  Kevin C. Johnson,et al.  5-Hydroxymethylcytosine localizes to enhancer elements and is associated with survival in glioblastoma patients , 2016, Nature Communications.

[44]  Stephen Yip,et al.  MSH6 Mutations Arise in Glioblastomas during Temozolomide Therapy and Mediate Temozolomide Resistance , 2009, Clinical Cancer Research.

[45]  Lei Han,et al.  Molecular classification of gliomas based on whole genome gene expression: a systematic report of 225 samples from the Chinese Glioma Cooperative Group. , 2012, Neuro-oncology.

[46]  T. Mikkelsen,et al.  Distinct epigenetic shift in a subset of Glioma CpG island methylator phenotype (G-CIMP) during tumor recurrence , 2017, bioRxiv.

[47]  Steven J. M. Jones,et al.  Mutational Analysis Reveals the Origin and Therapy-Driven Evolution of Recurrent Glioma , 2014, Science.

[48]  Chibo Hong,et al.  DNA Methylation and Somatic Mutations Converge on the Cell Cycle and Define Similar Evolutionary Histories in Brain Tumors. , 2015, Cancer cell.

[49]  J. Barnholtz-Sloan,et al.  CBTRUS statistical report: primary brain and central nervous system tumors diagnosed in the United States in 2007-2011. , 2012, Neuro-oncology.

[50]  L. Chin,et al.  Extrachromosal DNA elements can drive disease evolution in glioblastoma , 2016 .

[51]  Se Hoon Kim,et al.  Mesenchymal differentiation mediated by NF-κB promotes radiation resistance in glioblastoma. , 2013, Cancer cell.

[52]  Shawn M. Gillespie,et al.  Insulator dysfunction and oncogene activation in IDH mutant gliomas , 2015, Nature.

[53]  Jill S Barnholtz-Sloan,et al.  Whole-genome and multisector exome sequencing of primary and post-treatment glioblastoma reveals patterns of tumor evolution , 2015, Genome research.

[54]  S. Kwon,et al.  Recurrent Glioblastomas Reveal Molecular Subtypes Associated with Mechanistic Implications of Drug-Resistance , 2015, PloS one.

[55]  klaguia.  International Network of Cancer Genome Projects , 2010 .

[56]  Erwin G. Van Meir,et al.  Overcoming therapeutic resistance in glioblastoma: the way forward. , 2017, The Journal of clinical investigation.

[57]  J. Troge,et al.  Tumour evolution inferred by single-cell sequencing , 2011, Nature.

[58]  Wei Zhang,et al.  Genetic, epigenetic, and molecular landscapes of multifocal and multicentric glioblastoma , 2015, Acta Neuropathologica.

[59]  Emily J. Girard,et al.  Deep sequencing of multiple regions of glial tumors reveals spatial heterogeneity for mutations in clinically relevant genes , 2014, Genome Biology.

[60]  J. C. Love,et al.  EGFR variant heterogeneity in glioblastoma resolved through single-nucleus sequencing. , 2014, Cancer discovery.

[61]  Catherine Dumur,et al.  Microarray Analysis of MRI-defined Tissue Samples in Glioblastoma Reveals Differences in Regional Expression of Therapeutic Targets , 2006, Diagnostic molecular pathology : the American journal of surgical pathology, part B.

[62]  Gordon R. McInroy,et al.  Base resolution maps reveal the importance of 5-hydroxymethylcytosine in a human glioblastoma , 2017, npj Genomic Medicine.

[63]  Gary D Bader,et al.  International network of cancer genome projects , 2010, Nature.

[64]  M. J. van den Bent,et al.  Changes in the EGFR amplification and EGFRvIII expression between paired primary and recurrent glioblastomas. , 2015, Neuro-oncology.

[65]  Andrew P. Stubbs,et al.  Identification of Patients with Recurrent Glioblastoma Who May Benefit from Combined Bevacizumab and CCNU Therapy: A Report from the BELOB Trial. , 2016, Cancer research.

[66]  Debyani Chakravarty,et al.  Intratumoral heterogeneity of receptor tyrosine kinases EGFR and PDGFRA amplification in glioblastoma defines subpopulations with distinct growth factor response , 2012, Proceedings of the National Academy of Sciences.

[67]  Ian Law,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. , 2016, Neuro-oncology.

[68]  C. Melief,et al.  Cancer immunology. , 2011, Current opinion in immunology.

[69]  A. Vortmeyer,et al.  Integrated genomic characterization of IDH1-mutant glioma malignant progression , 2015, Nature Genetics.

[70]  Mariella G. Filbin,et al.  Decoupling genetics, lineages, and microenvironment in IDH-mutant gliomas by single-cell RNA-seq , 2017, Science.

[71]  Robert J Dempsey,et al.  Science Times , 2022 .

[72]  Benjamin D. Simons,et al.  Defining the mode of tumour growth by clonal analysis , 2012, Nature.

[73]  Yuchen Jiao,et al.  Mutations in CIC and FUBP1 Contribute to Human Oligodendroglioma , 2011, Science.

[74]  Mustafa Khasraw,et al.  Advances in the Treatment of Malignant Gliomas , 2010, Current oncology reports.

[75]  In-Hee Lee,et al.  Spatiotemporal genomic architecture informs precision oncology in glioblastoma , 2017, Nature Genetics.

[76]  D. Bensimon.  Participants List , 2006, Genetica.

[77]  Georg Langs,et al.  The DNA methylation landscape of glioblastoma disease progression shows extensive heterogeneity in time and space , 2017, Nature Medicine.

[78]  Hugues Sicotte,et al.  Genome-wide association study of glioma subtypes identifies specific differences in genetic susceptibility to glioblastoma and non-glioblastoma tumors , 2017, Nature Genetics.

[79]  In-Hee Lee,et al.  Spatiotemporal Evolution of the Primary Glioblastoma Genome. , 2015, Cancer cell.

[80]  T. Mikkelsen,et al.  A Distinct DNA Methylation Shift in a Subset of Glioma CpG Island Methylator Phenotypes during Tumor Recurrence , 2018, Cell reports.

[81]  Pieter Wesseling,et al.  International Society of Neuropathology‐Haarlem Consensus Guidelines for Nervous System Tumor Classification and Grading , 2014, Brain pathology.

[82]  Steven J. M. Jones,et al.  Molecular Profiling Reveals Biologically Discrete Subsets and Pathways of Progression in Diffuse Glioma , 2016, Cell.

[83]  Pieter Wesseling,et al.  Reconstructing the molecular life history of gliomas , 2017, bioRxiv.

[84]  David T. W. Jones,et al.  Hotspot mutations in H3F3A and IDH1 define distinct epigenetic and biological subgroups of glioblastoma. , 2012, Cancer cell.

[85]  Pieter Wesseling,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. , 2016, Neuro-oncology.

[86]  Rebecca A Betensky,et al.  Mosaic amplification of multiple receptor tyrosine kinase genes in glioblastoma. , 2011, Cancer cell.

[87]  S. Heath,et al.  A Comparison of RNA-Seq Results from Paired Formalin-Fixed Paraffin-Embedded and Fresh-Frozen Glioblastoma Tissue Samples , 2017, PloS one.

[88]  R. McLendon,et al.  Frequent ATRX, CIC, FUBP1 and IDH1 mutations refine the classification of malignant gliomas , 2012, Oncotarget.

[89]  Martin J. van den Bent,et al.  Radiotherapy plus concomitant and adjuvant temozolomide for glioblastoma. , 2005, The New England journal of medicine.

[90]  D. Haussler,et al.  The Somatic Genomic Landscape of Glioblastoma , 2013, Cell.

[91]  Steven J. M. Jones,et al.  Comprehensive, Integrative Genomic Analysis of Diffuse Lower-Grade Gliomas. , 2015, The New England journal of medicine.

[92]  F. Apiou,et al.  Molecular structure of double-minute chromosomes bearing amplified copies of the epidermal growth factor receptor gene in gliomas. , 2004, Proceedings of the National Academy of Sciences of the United States of America.

[93]  E. Schröck,et al.  Comprehensive molecular characterization of multifocal glioblastoma proves its monoclonal origin and reveals novel insights into clonal evolution and heterogeneity of glioblastomas , 2017, Neuro-oncology.

[94]  Longitudinal analysis of treatment-induced genomic alterations in gliomas , 2017, Genome Medicine.

[95]  Tracy T Batchelor,et al.  A hypermutation phenotype and somatic MSH6 mutations in recurrent human malignant gliomas after alkylator chemotherapy. , 2006, Cancer research.

[96]  S. Berger,et al.  IDH mutation impairs histone demethylation and results in a block to cell differentiation , 2012, Nature.

[97]  Erwin G. Van Meir,et al.  Exciting New Advances in Neuro‐Oncology: The Avenue to a Cure for Malignant Glioma , 2010, CA: a cancer journal for clinicians.

[98]  Shawn M. Gillespie,et al.  Single-cell RNA-seq highlights intratumoral heterogeneity in primary glioblastoma , 2014, Science.

[99]  Edward F. Chang,et al.  Tumor Evolution of Glioma-Intrinsic Gene Expression Subtypes Associates with Immunological Changes in the Microenvironment. , 2017, Cancer cell.

[100]  Satoru Miyano,et al.  Mutational landscape and clonal architecture in grade II and III gliomas , 2015, Nature Genetics.

[101]  Thomas D. Wu,et al.  Molecular subclasses of high-grade glioma predict prognosis, delineate a pattern of disease progression, and resemble stages in neurogenesis. , 2006, Cancer cell.