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Annual Review of Pathology: Mechanisms of Disease

Volume 11, 2016

Gliomas Genomics and Epigenomics: Arriving at the Start and Knowing It for the First Time

Abstract

Gliomas are the most common primary human brain tumors and occur in both adults and children. Over the past few years, systematic large-scale genomic and epigenomic profiling has provided unprecedented insight into their pathogenesis, uncovering alterations in an unanticipated number of genes and regulatory elements. In this review, we discuss recent discoveries about the genomics and epigenomics of adult and pediatric gliomas and highlight how some of the founding genetic mutations reshape the cancer epigenome. These studies provide an in-depth view of the molecular routes leading to glioma development, offer insight into the cancer stem cell model, help refine classifications, and should lay the foundation for improved clinical care.

Keyword(s): astrocytoma, diffuse intrinsic pontine glioma, glioblastoma, histone mutations, IDH1, oligodendroglioma
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/content/journals/10.1146/annurev-pathol-012615-044208
2016-05-23
2024-04-29
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Literature Cited

  1. Bailey P, Cushing H. 1.  1926. A Classification of the Tumors of the Glioma Group on a Histogenetic Basis with a Correlated Study of Prognosis Philadelphia: Lippincott
  2. Louis DN, Perry A, Burger P, Ellison DW, Reifenberger G. 2.  et al. 2014. International Society Of Neuropathology–Haarlem consensus guidelines for nervous system tumor classification and grading. Brain Pathol. 24:429–35 [Google Scholar]
  3. Stupp R, Mason WP, van den Bent MJ, Weller M, Fisher B. 3.  et al. 2005. Radiotherapy plus concomitant and adjuvant temozolomide for glioblastoma. N. Engl. J. Med. 352:987–96 [Google Scholar]
  4. Chinot OL, Wick W, Mason W, Henriksson R, Saran F. 4.  et al. 2014. Bevacizumab plus radiotherapy-temozolomide for newly diagnosed glioblastoma. N. Engl. J. Med. 370:709–22 [Google Scholar]
  5. Gilbert MR, Dignam JJ, Armstrong TS, Wefel JS, Blumenthal DT. 5.  et al. 2014. A randomized trial of bevacizumab for newly diagnosed glioblastoma. N. Engl. J. Med. 370:699–708 [Google Scholar]
  6. Slamon DJ, Leyland-Jones B, Shak S, Fuchs H, Paton V. 6.  et al. 2001. Use of chemotherapy plus a monoclonal antibody against HER2 for metastatic breast cancer that overexpresses HER2. N. Engl. J. Med. 344:783–92 [Google Scholar]
  7. Chapman PB, Hauschild A, Robert C, Haanen JB, Ascierto P. 7.  et al. 2011. Improved survival with vemurafenib in melanoma with BRAF V600E mutation. N. Engl. J. Med. 364:2507–16 [Google Scholar]
  8. Druker BJ, Talpaz M, Resta DJ, Peng B, Buchdunger E. 8.  et al. 2001. Efficacy and safety of a specific inhibitor of the BCR-ABL tyrosine kinase in chronic myeloid leukemia. N. Engl. J. Med. 344:1031–37 [Google Scholar]
  9. Lynch TJ, Bell DW, Sordella R, Gurubhagavatula S, Okimoto RA. 9.  et al. 2004. Activating mutations in the epidermal growth factor receptor underlying responsiveness of non-small-cell lung cancer to gefitinib. N. Engl. J. Med. 350:2129–39 [Google Scholar]
  10. Kwak EL, Bang YJ, Camidge DR, Shaw AT, Solomon B. 10.  et al. 2010. Anaplastic lymphoma kinase inhibition in non-small-cell lung cancer. N. Engl. J. Med. 363:1693–703 [Google Scholar]
  11. Cancer Genome Atlas Research Network, Brat DJ, Verhaak RG, Aldape KD, Yung WK. 11.  et al. 2015. Comprehensive, Integrative Genomic Analysis of Diffuse Lower-Grade Gliomas. N. Engl. J. Med. 372:2481–98 [Google Scholar]
  12. Dunn GP, Rinne ML, Wykosky J, Genovese G, Quayle SN. 12.  et al. 2012. Emerging insights into the molecular and cellular basis of glioblastoma. Genes Dev. 26:756–84 [Google Scholar]
  13. Brennan CW, Verhaak RG, McKenna A, Campos B, Noushmehr H. 13.  et al. 2013. The somatic genomic landscape of glioblastoma. Cell 155:462–77 [Google Scholar]
  14. Sugawa N, Ekstrand AJ, James CD, Collins VP. 14.  1990. Identical splicing of aberrant epidermal growth factor receptor transcripts from amplified rearranged genes in human glioblastomas. PNAS 87:8602–6 [Google Scholar]
  15. Schwechheimer K, Huang S, Cavenee WK. 15.  1995. EGFR gene amplification–rearrangement in human glioblastomas. Int. J. Cancer 62:145–48 [Google Scholar]
  16. Biernat W, Huang H, Yokoo H, Kleihues P, Ohgaki H. 16.  2004. Predominant expression of mutant EGFR (EGFRvIII) is rare in primary glioblastomas. Brain Pathol. 14:131–36 [Google Scholar]
  17. Wikstrand CJ, Reist CJ, Archer GE, Zalutsky MR, Bigner DD. 17.  1998. The class III variant of the epidermal growth factor receptor (EGFRvIII): characterization and utilization as an immunotherapeutic target. J. Neurovirol. 4:148–58 [Google Scholar]
  18. Furnari FB, Cloughesy TF, Cavenee WK, Mischel PS. 18.  2015. Heterogeneity of epidermal growth factor receptor signalling networks in glioblastoma. Nat. Rev. Cancer 15:302–10 [Google Scholar]
  19. Snuderl M, Fazlollahi L, Le LP, Nitta M, Zhelyazkova BH. 19.  et al. 2011. Mosaic amplification of multiple receptor tyrosine kinase genes in glioblastoma. Cancer Cell 20:810–17 [Google Scholar]
  20. Francis JM, Zhang CZ, Maire CL, Jung J, Manzo VE. 20.  et al. 2014. EGFR variant heterogeneity in glioblastoma resolved through single-nucleus sequencing. Cancer Discov. 4:956–71 [Google Scholar]
  21. Patel AP, Tirosh I, Trombetta JJ, Shalek AK, Gillespie SM. 21.  et al. 2014. Single-cell RNA-seq highlights intratumoral heterogeneity in primary glioblastoma. Science 344:1396–401 [Google Scholar]
  22. Sottoriva A, Spiteri I, Piccirillo SG, Touloumis A, Collins VP. 22.  et al. 2013. Intratumor heterogeneity in human glioblastoma reflects cancer evolutionary dynamics. PNAS 110:4009–14 [Google Scholar]
  23. Gill BJ, Pisapia DJ, Malone HR, Goldstein H, Lei L. 23.  et al. 2014. MRI-localized biopsies reveal subtype-specific differences in molecular and cellular composition at the margins of glioblastoma. PNAS 111:12550–55 [Google Scholar]
  24. Nathanson DA, Gini B, Mottahedeh J, Visnyei K, Koga T. 24.  et al. 2014. Targeted therapy resistance mediated by dynamic regulation of extrachromosomal mutant EGFR DNA. Science 343:616672–76 [Google Scholar]
  25. Parker BC, Annala MJ, Cogdell DE, Granberg KJ, Sun Y. 25.  et al. 2013. The tumorigenic FGFR3-TACC3 gene fusion escapes miR-99a regulation in glioblastoma. J. Clin. Investig. 123:855–65 [Google Scholar]
  26. Singh D, Chan JM, Zoppoli P, Niola F, Sullivan R. 26.  et al. 2012. Transforming fusions of FGFR and TACC genes in human glioblastoma. Science 337:1231–35 [Google Scholar]
  27. Frattini V, Trifonov V, Chan JM, Castano A, Lia M. 27.  et al. 2013. The integrated landscape of driver genomic alterations in glioblastoma. Nat. Genet. 45:1141–49 [Google Scholar]
  28. Schonberg DL, Bao S, Rich JN. 28.  2013. Genomics informs glioblastoma biology. Nat. Genet. 45:1105–7 [Google Scholar]
  29. Akhavan D, Pourzia AL, Nourian AA, Williams KJ, Nathanson D. 29.  et al. 2013. De-repression of PDGFRβ transcription promotes acquired resistance to EGFR tyrosine kinase inhibitors in glioblastoma patients. Cancer Discov. 3:534–47 [Google Scholar]
  30. Nathanson DA, Gini B, Mottahedeh J, Visnyei K, Koga T. 30.  et al. 2014. Targeted therapy resistance mediated by dynamic regulation of extrachromosomal mutant EGFR DNA. Science 343:72–76 [Google Scholar]
  31. Vivanco I, Robins HI, Rohle D, Campos C, Grommes C. 31.  et al. 2012. Differential sensitivity of glioma- versus lung cancer-specific EGFR mutations to EGFR kinase inhibitors. Cancer Discov. 2:458–71 [Google Scholar]
  32. Morris LG, Kaufman AM, Gong Y, Ramaswami D, Walsh LA. 32.  et al. 2013. Recurrent somatic mutation of FAT1 in multiple human cancers leads to aberrant Wnt activation. Nat. Genet. 45:253–61 [Google Scholar]
  33. Rheinbay E, Suva ML, Gillespie SM, Wakimoto H, Patel AP. 33.  et al. 2013. An aberrant transcription factor network essential for Wnt signaling and stem cell maintenance in glioblastoma. Cell Rep. 3:1567–79 [Google Scholar]
  34. Suva ML, Rheinbay E, Gillespie SM, Patel AP, Wakimoto H. 34.  et al. 2014. Reconstructing and reprogramming the tumor-propagating potential of glioblastoma stem-like cells. Cell 157:580–94 [Google Scholar]
  35. Bell RJ, Rube HT, Kreig A, Mancini A, Fouse SD. 35.  et al. 2015. The transcription factor GABP selectively binds and activates the mutant TERT promoter in cancer. Science 348:62381036–39 [Google Scholar]
  36. Schwartzentruber J, Korshunov A, Liu XY, Jones DT, Pfaff E. 36.  et al. 2012. Driver mutations in histone H3.3 and chromatin remodelling genes in paediatric glioblastoma. Nature 482:226–31 [Google Scholar]
  37. Jiao Y, Killela PJ, Reitman ZJ, Rasheed AB, Heaphy CM. 37.  et al. 2012. Frequent ATRX, CIC, FUBP1 and IDH1 mutations refine the classification of malignant gliomas. Oncotarget 3:709–22 [Google Scholar]
  38. Wu G, Diaz AK, Paugh BS, Rankin SL, Ju B. 38.  et al. 2014. The genomic landscape of diffuse intrinsic pontine glioma and pediatric non-brainstem high-grade glioma. Nat. Genet. 46:444–50 [Google Scholar]
  39. Parsons DW, Jones S, Zhang X, Lin JC, Leary RJ. 39.  et al. 2008. An integrated genomic analysis of human glioblastoma multiforme. Science 321:1807–12 [Google Scholar]
  40. Ohgaki H, Kleihues P. 40.  2011. Genetic profile of astrocytic and oligodendroglial gliomas. Brain Tumor Pathol. 28:177–83 [Google Scholar]
  41. Camelo-Piragua S, Jansen M, Ganguly A, Kim JC, Cosper AK. 41.  et al. 2011. A sensitive and specific diagnostic panel to distinguish diffuse astrocytoma from astrocytosis: Chromosome 7 gain with mutant isocitrate dehydrogenase 1 and p53. J. Neuropathol. Exp. Neurol. 70:110–15 [Google Scholar]
  42. Juratli TA, Kirsch M, Robel K, Soucek S, Geiger K. 42.  et al. 2012. IDH mutations as an early and consistent marker in low-grade astrocytomas WHO grade II and their consecutive secondary high-grade gliomas. J. Neuro-Oncol. 108:403–10 [Google Scholar]
  43. Kannan K, Inagaki A, Silber J, Gorovets D, Zhang J. 43.  et al. 2012. Whole-exome sequencing identifies ATRX mutation as a key molecular determinant in lower-grade glioma. Oncotarget 3:1194–203 [Google Scholar]
  44. Liu XY, Gerges N, Korshunov A, Sabha N, Khuong-Quang DA. 44.  et al. 2012. Frequent ATRX mutations and loss of expression in adult diffuse astrocytic tumors carrying IDH1/IDH2 and TP53 mutations. Acta Neuropathol. 124:615–25 [Google Scholar]
  45. Reuss DE, Sahm F, Schrimpf D, Wiestler B, Capper D. 45.  et al. 2015. 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. 129:133–46 [Google Scholar]
  46. Abedalthagafi M, Phillips JJ, Kim GE, Mueller S, Haas-Kogen DA. 46.  et al. 2013. The alternative lengthening of telomere phenotype is significantly associated with loss of ATRX expression in high-grade pediatric and adult astrocytomas: A multi-institutional study of 214 astrocytomas. Mod. Pathol. 26:1425–32 [Google Scholar]
  47. Koelsche C, Sahm F, Capper D, Reuss D, Sturm D. 47.  et al. 2013. Distribution of TERT promoter mutations in pediatric and adult tumors of the nervous system. Acta Neuropathol. 126:907–15 [Google Scholar]
  48. Fontebasso AM, Schwartzentruber J, Khuong-Quang DA, Liu XY, Sturm D. 48.  et al. 2013. Mutations in SETD2 and genes affecting histone H3K36 methylation target hemispheric high-grade gliomas. Acta Neuropathol. 125:659–69 [Google Scholar]
  49. Chi AS, Batchelor TT, Yang D, Dias-Santagata D, Borger DR. 49.  et al. 2013. BRAF V600E mutation identifies a subset of low-grade diffusely infiltrating gliomas in adults. J. Clin. Oncol. 31:e233–36 [Google Scholar]
  50. Bettegowda C, Agrawal N, Jiao Y, Sausen M, Wood LD. 50.  et al. 2011. Mutations in CIC and FUBP1 contribute to human oligodendroglioma. Science 333:1453–55 [Google Scholar]
  51. Yip S, Butterfield YS, Morozova O, Chittaranjan S, Blough MD. 51.  et al. 2012. Concurrent CIC mutations, IDH mutations, and 1p/19q loss distinguish oligodendrogliomas from other cancers. J. Pathol. 226:7–16 [Google Scholar]
  52. Badiali M, Gleize V, Paris S, Moi L, Elhouadani S. 52.  et al. 2012. KIAA1549-BRAF fusions and IDH mutations can coexist in diffuse gliomas of adults. Brain Pathol. 22:841–47 [Google Scholar]
  53. Kim YH, Nonoguchi N, Paulus W, Brokinkel B, Keyvani K. 53.  et al. 2012. Frequent BRAF gain in low-grade diffuse gliomas with 1p/19q loss. Brain Pathol. 22:834–40 [Google Scholar]
  54. Zhang J, Wu G, Miller CP, Tatevossian RG, Dalton JD. 54.  et al. 2013. Whole-genome sequencing identifies genetic alterations in pediatric low-grade gliomas. Nat. Genet. 45:602–12 [Google Scholar]
  55. Cruz GR, Dias Oliveira I, Moraes L, Del Giudice Paniago M, de Seixas Alves MT. 55.  et al. 2014. Analysis of KIAA1549-BRAF fusion gene expression and IDH1/IDH2 mutations in low grade pediatric astrocytomas. J. Neuro-Oncol. 117:235–42 [Google Scholar]
  56. Nakamura M, Shimada K, Ishida E, Higuchi T, Nakase H. 56.  et al. 2007. Molecular pathogenesis of pediatric astrocytic tumors. Neuro-Oncology 9:113–23 [Google Scholar]
  57. Deshmukh H, Yeh TH, Yu J, Sharma MK, Perry A. 57.  et al. 2008. High-resolution, dual-platform aCGH analysis reveals frequent HIPK2 amplification and increased expression in pilocytic astrocytomas. Oncogene 27:4745–51 [Google Scholar]
  58. Hoischen A, Ehrler M, Fassunke J, Simon M, Baudis M. 58.  et al. 2008. Comprehensive characterization of genomic aberrations in gangliogliomas by CGH, array-based CGH and interphase FISH. Brain Pathol. 18:326–37 [Google Scholar]
  59. Jacob K, Albrecht S, Sollier C, Faury D, Sader E. 59.  et al. 2009. Duplication of 7q34 is specific to juvenile pilocytic astrocytomas and a hallmark of cerebellar and optic pathway tumours. Br. J. Cancer 101:722–33 [Google Scholar]
  60. Pfister S, Janzarik WG, Remke M, Ernst A, Werft W. 60.  et al. 2008. BRAF gene duplication constitutes a mechanism of MAPK pathway activation in low-grade astrocytomas. J. Clin. Investig. 118:1739–49 [Google Scholar]
  61. Sievert AJ, Jackson EM, Gai X, Hakonarson H, Judkins AR. 61.  et al. 2009. Duplication of 7q34 in pediatric low-grade astrocytomas detected by high-density single-nucleotide polymorphism-based genotype arrays results in a novel BRAF fusion gene. Brain Pathol. 19:449–58 [Google Scholar]
  62. Forshew T, Tatevossian RG, Lawson AR, Ma J, Neale G. 62.  et al. 2009. Activation of the ERK/MAPK pathway: A signature genetic defect in posterior fossa pilocytic astrocytomas. J. Pathol. 218:172–81 [Google Scholar]
  63. Lin A, Rodriguez FJ, Karajannis MA, Williams SC, Legault G. 63.  et al. 2012. BRAF alterations in primary glial and glioneuronal neoplasms of the central nervous system with identification of 2 novel KIAA1549:BRAF fusion variants. J. Neuropathol. Exp. Neurol. 71:66–72 [Google Scholar]
  64. Jones DT, Kocialkowski S, Liu L, Pearson DM, Ichimura K, Collins VP. 64.  2009. Oncogenic RAF1 rearrangement and a novel BRAF mutation as alternatives to KIAA1549:BRAF fusion in activating the MAPK pathway in pilocytic astrocytoma. Oncogene 28:2119–23 [Google Scholar]
  65. Cin H, Meyer C, Herr R, Janzarik WG, Lambert S. 65.  et al. 2011. Oncogenic FAM131B-BRAF fusion resulting from 7q34 deletion comprises an alternative mechanism of MAPK pathway activation in pilocytic astrocytoma. Acta Neuropathol. 121:763–74 [Google Scholar]
  66. Jones DT, Hutter B, Jager N, Korshunov A, Kool M. 66.  et al. 2013. Recurrent somatic alterations of FGFR1 and NTRK2 in pilocytic astrocytoma. Nat. Genet. 45:927–32 [Google Scholar]
  67. Sharma MK, Zehnbauer BA, Watson MA, Gutmann DH. 67.  2005. RAS pathway activation and an oncogenic RAS mutation in sporadic pilocytic astrocytoma. Neurology 65:1335–36 [Google Scholar]
  68. Janzarik WG, Kratz CP, Loges NT, Olbrich H, Klein C. 68.  et al. 2007. Further evidence for a somatic KRAS mutation in a pilocytic astrocytoma. Neuropediatrics 38:61–63 [Google Scholar]
  69. DeClue JE, Papageorge AG, Fletcher JA, Diehl SR, Ratner N. 69.  et al. 1992. Abnormal regulation of mammalian p21ras contributes to malignant tumor growth in von Recklinghausen (type 1) neurofibromatosis. Cell 69:265–73 [Google Scholar]
  70. Tatevossian RG, Tang B, Dalton J, Forshew T, Lawson AR. 70.  et al. 2010. MYB upregulation and genetic aberrations in a subset of pediatric low-grade gliomas. Acta Neuropathol. 120:731–43 [Google Scholar]
  71. Ramkissoon LA, Horowitz PM, Craig JM, Ramkissoon SH, Rich BE. 71.  et al. 2013. Genomic analysis of diffuse pediatric low-grade gliomas identifies recurrent oncogenic truncating rearrangements in the transcription factor MYBL1. PNAS 110:8188–93 [Google Scholar]
  72. Jones C, Baker SJ. 72.  2014. Unique genetic and epigenetic mechanisms driving paediatric diffuse high-grade glioma. Nat. Rev. Cancer 14:551–61 [Google Scholar]
  73. Roujeau T, Machado G, Garnett MR, Miquel C, Puget S. 73.  et al. 2007. Stereotactic biopsy of diffuse pontine lesions in children. J. Neurosurg. 107:1–4 [Google Scholar]
  74. Wu G, Broniscer A, McEachron TA, Lu C, Paugh BS. 74.  et al. 2012. Somatic histone H3 alterations in pediatric diffuse intrinsic pontine gliomas and non-brainstem glioblastomas. Nat. Genet. 44:251–53 [Google Scholar]
  75. Sturm D, Witt H, Hovestadt V, Khuong-Quang DA, Jones DT. 75.  et al. 2012. Hotspot mutations in H3F3A and IDH1 define distinct epigenetic and biological subgroups of glioblastoma. Cancer Cell 22:425–37 [Google Scholar]
  76. Bjerke L, Mackay A, Nandhabalan M, Burford A, Jury A. 76.  et al. 2013. Histone H3.3. mutations drive pediatric glioblastoma through upregulation of MYCN. Cancer Discov. 3:512–19 [Google Scholar]
  77. Buczkowicz P, Hoeman C, Rakopoulos P, Pajovic S, Letourneau L. 77.  et al. 2014. Genomic analysis of diffuse intrinsic pontine gliomas identifies three molecular subgroups and recurrent activating ACVR1 mutations. Nat. Genet. 46:451–56 [Google Scholar]
  78. Taylor KR, Mackay A, Truffaux N, Butterfield YS, Morozova O. 78.  et al. 2014. Recurrent activating ACVR1 mutations in diffuse intrinsic pontine glioma. Nat. Genet. 46:457–61 [Google Scholar]
  79. Fontebasso AM, Papillon-Cavanagh S, Schwartzentruber J, Nikbakht H, Gerges N. 79.  et al. 2014. Recurrent somatic mutations in ACVR1 in pediatric midline high-grade astrocytoma. Nat. Genet. 46:462–66 [Google Scholar]
  80. Lee J, Son MJ, Woolard K, Donin NM, Li A. 80.  et al. 2008. Epigenetic-mediated dysfunction of the bone morphogenetic protein pathway inhibits differentiation of glioblastoma-initiating cells. Cancer Cell 13:69–80 [Google Scholar]
  81. Piccirillo SG, Reynolds BA, Zanetti N, Lamorte G, Binda E. 81.  et al. 2006. Bone morphogenetic proteins inhibit the tumorigenic potential of human brain tumour-initiating cells. Nature 444:761–65 [Google Scholar]
  82. Paugh BS, Qu C, Jones C, Liu Z, Adamowicz-Brice M. 82.  et al. 2010. Integrated molecular genetic profiling of pediatric high-grade gliomas reveals key differences with the adult disease. J. Clin. Oncol. 28:3061–68 [Google Scholar]
  83. Baylin SB, Jones PA. 83.  2011. A decade of exploring the cancer epigenome—biological and translational implications. Nat. Rev. Cancer 11:726–34 [Google Scholar]
  84. Dawson MA, Kouzarides T. 84.  2012. Cancer epigenetics: From mechanism to therapy. Cell 150:12–27 [Google Scholar]
  85. Mack SC, Witt H, Piro RM, Gu L, Zuyderduyn S. 85.  et al. 2014. Epigenomic alterations define lethal CIMP-positive ependymomas of infancy. Nature 506:445–50 [Google Scholar]
  86. Suva ML, Riggi N, Bernstein BE. 86.  2013. Epigenetic reprogramming in cancer. Science 339:1567–70 [Google Scholar]
  87. Sturm D, Bender S, Jones DT, Lichter P, Grill J. 87.  et al. 2014. Paediatric and adult glioblastoma: Multiform (epi)genomic culprits emerge. Nat. Rev. Cancer 14:92–107 [Google Scholar]
  88. Mazor T, Pankov A, Johnson BE, Hong C, Hamilton EG. 88.  et al. 2015. DNA methylation and somatic mutations converge on the cell cycle and define similar evolutionary histories in brain tumors. Cancer Cell 28:3307–17 [Google Scholar]
  89. Liu F, Hon GC, Villa GR, Turner KM, Ikegami S. 89.  et al. 2015. EGFR mutation promotes glioblastoma through epigenome and transcription factor network remodeling. Mol. Cell 60:2307–18 [Google Scholar]
  90. de Vries NA, Hulsman D, Akhtar W, de Jong J, Miles DC. 90.  et al. 2015. Prolonged Ezh2 depletion in glioblastoma causes a robust switch in cell fate resulting in tumor progression. Cell Rep. 10:383–97 [Google Scholar]
  91. Losman JA, Kaelin WG Jr. 91.  2013. What a difference a hydroxyl makes: Mutant IDH, (R)-2-hydroxyglutarate, and cancer. Genes Dev. 27:836–52 [Google Scholar]
  92. Yan H, Parsons DW, Jin G, McLendon R, Rasheed BA. 92.  et al. 2009. IDH1 and IDH2 mutations in gliomas. N. Engl. J. Med. 360:765–73 [Google Scholar]
  93. Turcan S, Rohle D, Goenka A, Walsh LA, Fang F. 93.  et al. 2012. IDH1 mutation is sufficient to establish the glioma hypermethylator phenotype. Nature 483:479–83 [Google Scholar]
  94. Dang L, White DW, Gross S, Bennett BD, Bittinger MA. 94.  et al. 2009. Cancer-associated IDH1 mutations produce 2-hydroxyglutarate. Nature 462:739–44 [Google Scholar]
  95. Figueroa ME, Abdel-Wahab O, Lu C, Ward PS, Patel J. 95.  et al. 2010. Leukemic IDH1 and IDH2 mutations result in a hypermethylation phenotype, disrupt TET2 function, and impair hematopoietic differentiation. Cancer Cell 18:553–67 [Google Scholar]
  96. Ko M, Huang Y, Jankowska AM, Pape UJ, Tahiliani M. 96.  et al. 2010. Impaired hydroxylation of 5-methylcytosine in myeloid cancers with mutant TET2. Nature 468:839–43 [Google Scholar]
  97. Kim YH, Pierscianek D, Mittelbronn M, Vital A, Mariani L. 97.  et al. 2011. TET2 promoter methylation in low-grade diffuse gliomas lacking IDH1/2 mutations. J. Clin. Pathol. 64:850–52 [Google Scholar]
  98. Flavahan WA, Drier Y, Liau BB, Gillespie SM, Venteicher AS. 98.  et al. 2016. Insulator dysfunction and oncogene activation in IDH mutant gliomas. Nature 529:110–14 [Google Scholar]
  99. Wick W, Weller M, van den Bent M, Sanson M, Weiler M. 99.  et al. 2014. MGMT testing—the challenges for biomarker-based glioma treatment. Nat. Rev. Neurol. 10:372–85 [Google Scholar]
  100. Wick W, Platten M, Meisner C, Felsberg J, Tabatabai G. 100.  et al. 2012. Temozolomide chemotherapy alone versus radiotherapy alone for malignant astrocytoma in the elderly: The NOA-08 randomised, phase 3 trial. Lancet Oncol. 13:707–15 [Google Scholar]
  101. 101. Cancer Genome Atlas Res. Netw 2008. Comprehensive genomic characterization defines human glioblastoma genes and core pathways. Nature 455:1061–68 [Google Scholar]
  102. Verhaak RG, Hoadley KA, Purdom E, Wang V, Qi Y. 102.  et al. 2010. Integrated genomic analysis identifies clinically relevant subtypes of glioblastoma characterized by abnormalities in PDGFRA, IDH1, EGFR, and NF1. Cancer Cell 17:98–110 [Google Scholar]
  103. Yuen BT, Knoepfler PS. 103.  2013. Histone H3.3 mutations: A variant path to cancer. Cancer Cell 24:567–74 [Google Scholar]
  104. Jenuwein T, Allis CD. 104.  2001. Translating the histone code. Science 293:1074–80 [Google Scholar]
  105. Lewis PW, Muller MM, Koletsky MS, Cordero F, Lin S. 105.  et al. 2013. Inhibition of PRC2 activity by a gain-of-function H3 mutation found in pediatric glioblastoma. Science 340:857–61 [Google Scholar]
  106. Venneti S, Garimella MT, Sullivan LM, Martinez D, Huse JT. 106.  et al. 2013. Evaluation of histone 3 lysine 27 trimethylation (H3K27me3) and enhancer of Zest 2 (EZH2) in pediatric glial and glioneuronal tumors shows decreased H3K27me3 in H3F3A K27M mutant glioblastomas. Brain Pathol. 23:558–64 [Google Scholar]
  107. Herz HM, Morgan M, Gao X, Jackson J, Rickels R. 107.  et al. 2014. Histone H3 lysine-to-methionine mutants as a paradigm to study chromatin signaling. Science 345:1065–70 [Google Scholar]
  108. Chan KM, Fang D, Gan H, Hashizume R, Yu C. 108.  et al. 2013. The histone H3.3K27M mutation in pediatric glioma reprograms H3K27 methylation and gene expression. Genes Dev. 27:985–90 [Google Scholar]
  109. Suva ML, Riggi N, Janiszewska M, Radovanovic I, Provero P. 109.  et al. 2009. EZH2 is essential for glioblastoma cancer stem cell maintenance. Cancer Res. 69:9211–18 [Google Scholar]
  110. Funato K, Major T, Lewis PW, Allis CD, Tabar V. 110.  2014. Use of human embryonic stem cells to model pediatric gliomas with H3.3K27M histone mutation. Science 346:1529–33 [Google Scholar]
  111. Hashizume R, Andor N, Ihara Y, Lerner R, Gan H. 111.  et al. 2014. Pharmacologic inhibition of histone demethylation as a therapy for pediatric brainstem glioma. Nat. Med. 20:1394–96 [Google Scholar]
  112. Grasso CS, Tang Y, Truffaux N, Berlow NE, Liu L. 112.  et al. 2015. Functionally defined therapeutic targets in diffuse intrinsic pontine glioma. Nat. Med. 21:6555–59 [Google Scholar]
  113. Cheung NK, Zhang J, Lu C, Parker M, Bahrami A. 113.  et al. 2012. Association of age at diagnosis and genetic mutations in patients with neuroblastoma. JAMA 307:1062–71 [Google Scholar]
  114. Lu C, Ward PS, Kapoor GS, Rohle D, Turcan S. 114.  et al. 2012. IDH mutation impairs histone demethylation and results in a block to cell differentiation. Nature 483:474–78 [Google Scholar]
  115. Kreso A, Dick JE. 115.  2014. Evolution of the cancer stem cell model. Cell Stem Cell 14:275–91 [Google Scholar]
  116. Meacham CE, Morrison SJ. 116.  2013. Tumour heterogeneity and cancer cell plasticity. Nature 501:328–37 [Google Scholar]
  117. Nguyen LV, Vanner R, Dirks P, Eaves CJ. 117.  2012. Cancer stem cells: An evolving concept. Nat. Rev. Cancer 12:133–43 [Google Scholar]
  118. Bao S, Wu Q, McLendon RE, Hao Y, Shi Q. 118.  et al. 2006. Glioma stem cells promote radioresistance by preferential activation of the DNA damage response. Nature 444:756–60 [Google Scholar]
  119. Diehn M, Cho RW, Lobo NA, Kalisky T, Dorie MJ. 119.  et al. 2009. Association of reactive oxygen species levels and radioresistance in cancer stem cells. Nature 458:780–83 [Google Scholar]
  120. Chen R, Nishimura MC, Bumbaca SM, Kharbanda S, Forrest WF. 120.  et al. 2010. A hierarchy of self-renewing tumor-initiating cell types in glioblastoma. Cancer Cell 17:362–75 [Google Scholar]
  121. Ben-Porath I, Thomson MW, Carey VJ, Ge R, Bell GW. 121.  et al. 2008. An embryonic stem cell-like gene expression signature in poorly differentiated aggressive human tumors. Nat. Genet. 40:499–507 [Google Scholar]
  122. Lathia JD, Mack SC, Mulkearns-Hubert EE, Valentim CL, Rich JN. 122.  2015. Cancer stem cells in glioblastoma. Genes Dev 29:121203–17 [Google Scholar]
  123. Anido J, Saez-Borderias A, Gonzalez-Junca A, Rodon L, Folch G. 123.  et al. 2010. TGF-β receptor inhibitors target the CD44high/Id1high glioma-initiating cell population in human glioblastoma. Cancer Cell 18:655–68 [Google Scholar]
  124. Chen J, Li Y, Yu TS, McKay RM, Burns DK. 124.  et al. 2012. A restricted cell population propagates glioblastoma growth after chemotherapy. Nature 488:522–26 [Google Scholar]
  125. Lathia JD, Gallagher J, Heddleston JM, Wang J, Eyler CE. 125.  et al. 2010. Integrin alpha 6 regulates glioblastoma stem cells. Cell Stem Cell 6:421–32 [Google Scholar]
  126. Singh SK, Hawkins C, Clarke ID, Squire JA, Bayani J. 126.  et al. 2004. Identification of human brain tumour initiating cells. Nature 432:396–401 [Google Scholar]
  127. Son MJ, Woolard K, Nam DH, Lee J, Fine HA. 127.  2009. SSEA-1 is an enrichment marker for tumor-initiating cells in human glioblastoma. Cell Stem Cell 4:440–52 [Google Scholar]
  128. Stricker SH, Feber A, Engstrom PG, Caren H, Kurian KM. 128.  et al. 2013. Widespread resetting of DNA methylation in glioblastoma-initiating cells suppresses malignant cellular behavior in a lineage-dependent manner. Genes Dev. 27:654–69 [Google Scholar]
  129. Schonberg DL, Miller TE, Wu Q, Flavahan WA, Das NK. 129.  et al. 2015. Preferential iron trafficking characterizes glioblastoma stem-like cells. Cancer Cell 28:4441–55 [Google Scholar]
  130. Hitomi M, Deleyrolle LP, Mulkearns-Hubert EE, Jarrar A, Li M. 130.  et al. 2015. Differential connexin function enhances self-renewal in glioblastoma. Cell Rep 11:71031–42 [Google Scholar]
  131. Chaffer CL, Marjanovic ND, Lee T, Bell G, Kleer CG. 131.  et al. 2013. Poised chromatin at the ZEB1 promoter enables breast cancer cell plasticity and enhances tumorigenicity. Cell 154:61–74 [Google Scholar]
  132. Roesch A, Fukunaga-Kalabis M, Schmidt EC, Zabierowski SE, Brafford PA. 132.  et al. 2010. A temporarily distinct subpopulation of slow-cycling melanoma cells is required for continuous tumor growth. Cell 141:583–94 [Google Scholar]
  133. Friedmann-Morvinski D, Bushong EA, Ke E, Soda Y, Marumoto T. 133.  et al. 2012. Dedifferentiation of neurons and astrocytes by oncogenes can induce gliomas in mice. Science 338:1080–84 [Google Scholar]
  134. Holland EC, Hively WP, DePinho RA, Varmus HE. 134.  1998. A constitutively active epidermal growth factor receptor cooperates with disruption of G1 cell-cycle arrest pathways to induce glioma-like lesions in mice. Genes Dev. 12:3675–85 [Google Scholar]
  135. Liu C, Sage JC, Miller MR, Verhaak RG, Hippenmeyer S. 135.  et al. 2011. Mosaic analysis with double markers reveals tumor cell of origin in glioma. Cell 146:209–21 [Google Scholar]
  136. Eppert K, Takenaka K, Lechman ER, Waldron L, Nilsson B. 136.  et al. 2011. Stem cell gene expression programs influence clinical outcome in human leukemia. Nat. Med. 17:1086–93 [Google Scholar]
  137. Yachida S, Jones S, Bozic I, Antal T, Leary R. 137.  et al. 2010. Distant metastasis occurs late during the genetic evolution of pancreatic cancer. Nature 467:1114–17 [Google Scholar]
  138. Patel AP, Tirosh I, Trombetta JJ, Shalek AK, Gillespie SM. 138.  et al. 2014. Single-cell RNA-seq highlights intratumoral heterogeneity in primary glioblastoma. Science 344:1396–401 [Google Scholar]
  139. Jeuken JW, von Deimling A, Wesseling P. 139.  2004. Molecular pathogenesis of oligodendroglial tumors. J. Neuro-Oncol. 70:161–81 [Google Scholar]
  140. Bello MJ, Leone PE, Vaquero J, de Campos JM, Kusak ME. 140.  et al. 1995. Allelic loss at 1p and 19q frequently occurs in association and may represent early oncogenic events in oligodendroglial tumors. Int. J. Cancer 64:207–10 [Google Scholar]
  141. Kraus JA, Koopmann J, Kaskel P, Maintz D, Brandner S. 141.  et al. 1995. Shared allelic losses on chromosomes 1p and 19q suggest a common origin of oligodendroglioma and oligoastrocytoma. J. Neuropathol. Exp. Neurol. 54:91–95 [Google Scholar]
  142. Bax DA, Mackay A, Little SE, Carvalho D, Viana-Pereira M. 142.  et al. 2010. A distinct spectrum of copy number aberrations in pediatric high-grade gliomas. Clin. Cancer Res. 16:3368–77 [Google Scholar]
  143. Neumann E, Kalousek DK, Norman MG, Steinbok P, Cochrane DD, Goddard K. 143.  1993. Cytogenetic analysis of 109 pediatric central nervous system tumors. Cancer Genet. Cytogenet. 71:40–49 [Google Scholar]
  144. White FV, Anthony DC, Yunis EJ, Tarbell NJ, Scott RM, Schofield DE. 144.  1995. Nonrandom chromosomal gains in pilocytic astrocytomas of childhood. Hum. Pathol. 26:979–86 [Google Scholar]
  145. Zattara-Cannoni H, Gambarelli D, Lena G, Dufour H, Choux M. 145.  et al. 1998. Are juvenile pilocytic astrocytomas benign tumors? A cytogenetic study in 24 cases. Cancer Genet. Cytogenet. 104:157–60 [Google Scholar]
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Gliomas Genomics and Epigenomics: Arriving at the Start and Knowing It for the First Time
Annual Review of Pathology: Mechanisms of Disease 11, 497 (2016); https://doi.org/10.1146/annurev-pathol-012615-044208
/content/journals/10.1146/annurev-pathol-012615-044208
/content/journals/10.1146/annurev-pathol-012615-044208
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