1932

Abstract

The human brain contains a vast number of cells and shows extraordinary cellular diversity to facilitate the many cognitive and automatic commands governing our bodily functions. This complexity arises partly from large-scale structural variations in the genome, evolutionary processes to increase brain size, function, and cognition. Not surprisingly given recent technical advances, low-grade gliomas (LGGs), which arise from the glia (the most abundant cell type in the brain), have undergone a recent revolution in their classification and therapy, especially in the pediatric setting. Next-generation sequencing has uncovered previously unappreciated diverse LGG entities, unraveling genetic subgroups and multiple molecular alterations and altered pathways, including many amenable to therapeutic targeting. In this article we review these novel entities, in which oncogenic processes show striking age-related neuroanatomical specificity (highlighting their close interplay with development); the opportunities they provide for targeted therapies, some of which are already practiced at the bedside; and the challenges of implementing molecular pathology in the clinic.

Loading

Article metrics loading...

/content/journals/10.1146/annurev-genet-120417-031642
2019-12-03
2024-03-28
Loading full text...

Full text loading...

/deliver/fulltext/genet/53/1/annurev-genet-120417-031642.html?itemId=/content/journals/10.1146/annurev-genet-120417-031642&mimeType=html&fmt=ahah

Literature Cited

  1. 1. 
    Bandopadhayay P, Bergthold G, London WB, Goumnerova LC, Morales La Madrid A et al. 2014. Long-term outcome of 4,040 children diagnosed with pediatric low-grade gliomas: an analysis of the Surveillance Epidemiology and End Results (SEER) database. Pediatr. Blood Cancer 61:1173–79
    [Google Scholar]
  2. 2. 
    Bandopadhayay P, Meyerson M. 2018. Landscapes of childhood tumours. Nature 555:316–17
    [Google Scholar]
  3. 3. 
    Bandopadhayay P, Ramkissoon LA, Jain P, Bergthold G, Wala J et al. 2016. MYB-QKI rearrangements in angiocentric glioma drive tumorigenicity through a tripartite mechanism. Nat. Genet. 48:273–82
    [Google Scholar]
  4. 4. 
    Banerjee A, Jakacki RI, Onar-Thomas A, Wu S, Nicolaides T et al. 2017. A phase I trial of the MEK inhibitor selumetinib (AZD6244) in pediatric patients with recurrent or refractory low-grade glioma: a Pediatric Brain Tumor Consortium (PBTC) study. Neuro-Oncology 19:1135–44
    [Google Scholar]
  5. 5. 
    Bridge JA, Liu X-Q, Sumegi J, Nelson M, Reyes C et al. 2013. Identification of a novel, recurrent SLC44A1-PRKCA fusion in papillary glioneuronal tumor. Brain Pathol 23:121–28
    [Google Scholar]
  6. 6. 
    Brody BA, Kinney HC, Kloman AS, Gilles FH 1987. Sequence of central nervous system myelination in human infancy. I. An autopsy study of myelination. J. Neuropathol. Exp. Neurol. 46:283–301
    [Google Scholar]
  7. 7. 
    Cancer Genome Atlas Research Network Brat DJ, Verhaak RG, Aldape KD, Yung WK et al. 2015. Comprehensive, integrative genomic analysis of diffuse lower-grade gliomas. New Engl. J. Med. 372:2481–98
    [Google Scholar]
  8. 8. 
    Capper D, Jones DTW, Sill M, Hovestadt V, Schrimpf D et al. 2018. DNA methylation-based classification of central nervous system tumours. Nature 555:469–74
    [Google Scholar]
  9. 9. 
    Chatterjee D, Garg C, Singla N, Radotra BD 2018. Desmoplastic non-infantile astrocytoma/ganglioglioma: rare low-grade tumor with frequent BRAF V600E mutation. Hum. Pathol. 80:186–91
    [Google Scholar]
  10. 10. 
    Chiang JCH, Harreld JH, Orr BA, Sharma S, Ismail A et al. 2017. Low-grade spinal glioneuronal tumors with BRAF gene fusion and 1p deletion but without leptomeningeal dissemination. Acta Neuropathol 134:159–62
    [Google Scholar]
  11. 11. 
    Dang L, White DW, Gross S, Bennett BD, Bittinger MA et al. 2009. Cancer-associated IDH1 mutations produce 2-hydroxyglutarate. Nature 462:739–44
    [Google Scholar]
  12. 12. 
    de Blank PMK, Fisher MJ, Liu GT, Gutmann DH, Listernick R et al. 2017. Optic pathway gliomas in neurofibromatosis type 1. An update: surveillance, treatment indications, and biomarkers of vision. J. Neuroophthalmol. 37:Suppl. 1S23–32
    [Google Scholar]
  13. 13. 
    Deng MY, Sill M, Chiang J, Schittenhelm J, Ebinger M et al. 2018. Molecularly defined diffuse leptomeningeal glioneuronal tumor (DLGNT) comprises two subgroups with distinct clinical and genetic features. Acta Neuropathol 136:239–53
    [Google Scholar]
  14. 14. 
    Eckel-Passow JE, Lachance DH, Molinaro AM, Walsh KM, Decker PA et al. 2015. Glioma groups based on 1p/19q, IDH, and TERT promoter mutations in tumors. New Engl. J. Med. 372:2499–508
    [Google Scholar]
  15. 15. 
    Ellezam B, Theeler BJ, Luthra R, Adesina AM, Aldape KD, Gilbert MR 2012. Recurrent PIK3CA mutations in rosette-forming glioneuronal tumor. Acta Neuropathol 123:285–87
    [Google Scholar]
  16. 16. 
    Fiset PO, Fontebasso AM, De Jay N, Gayden T, Nikbakht H et al. 2017. Longitudinal mutational analysis of a cerebellar pilocytic astrocytoma recurring as a ganglioglioma. Pediatr. Blood Cancer 64:275–78
    [Google Scholar]
  17. 17. 
    Fontebasso AM, Bechet D, Jabado N 2013. Molecular biomarkers in pediatric glial tumors: a needed wind of change. Curr. Opin. Oncol. 25:665–73
    [Google Scholar]
  18. 18. 
    Fontebasso AM, Gayden T, Nikbakht H, Neirinck M, Papillon-Cavanagh S et al. 2014. Epigenetic dysregulation: a novel pathway of oncogenesis in pediatric brain tumors. Acta Neuropathol 128:615–27
    [Google Scholar]
  19. 19. 
    Fontebasso AM, Jabado N. 2015. Pediatric brain tumors: Genomics and epigenomics pave the way. Crit. Rev. Oncogen. 20:271–99
    [Google Scholar]
  20. 20. 
    Fontebasso AM, Papillon-Cavanagh S, Schwartzentruber J, Nikbakht H, Gerges N et al. 2014. Recurrent somatic mutations in ACVR1 in pediatric midline high-grade astrocytoma. Nat. Genet. 46:462–66
    [Google Scholar]
  21. 21. 
    Fontebasso AM, Shirinian M, Khuong-Quang DA, Bechet D, Gayden T et al. 2015. Non-random aneuploidy specifies subgroups of pilocytic astrocytoma and correlates with older age. Oncotarget 6:31844–56
    [Google Scholar]
  22. 22. 
    Franz DN, Belousova E, Sparagana S, Bebin EM, Frost M et al. 2013. Efficacy and safety of everolimus for subependymal giant cell astrocytomas associated with tuberous sclerosis complex (EXIST-1): a multicentre, randomised, placebo-controlled phase 3 trial. Lancet 381:125–32
    [Google Scholar]
  23. 23. 
    Franz DN, Belousova E, Sparagana S, Bebin EM, Frost M et al. 2014. Everolimus for subependymal giant cell astrocytoma in patients with tuberous sclerosis complex: 2-year open-label extension of the randomised EXIST-1 study. Lancet Oncol 15:1513–20
    [Google Scholar]
  24. 24. 
    Fryssira H, Leventopoulos G, Psoni S, Kitsiou-Tzeli S, Stavrianeas N, Kanavakis E 2008. Tumor development in three patients with Noonan syndrome. Eur. J. Pediatr. 167:1025–31
    [Google Scholar]
  25. 25. 
    Fuller CE, Jones DTW, Kieran MW 2017. New classification for central nervous system tumors: implications for diagnosis and therapy. Am. Soc. Clin. Oncol. Educ. Book 37:753–63
    [Google Scholar]
  26. 26. 
    Gardiman MP, Fassan M, Orvieto E, D'Avella D, Denaro L et al. 2010. Diffuse leptomeningeal glioneuronal tumors: a new entity?. Brain Pathol 20:361–66
    [Google Scholar]
  27. 27. 
    Gessi M, Moneim YA, Hammes J, Goschzik T, Scholz M et al. 2014. FGFR1 mutations in rosette-forming glioneuronal tumors of the fourth ventricle. J. Neuropathol. Exp. Neurol. 73:580–84
    [Google Scholar]
  28. 28. 
    Gonzalez-Quevedo R, Lee Y, Poss KD, Wilkinson DG 2010. Neuronal regulation of the spatial patterning of neurogenesis. Dev. Cell 18:136–47
    [Google Scholar]
  29. 29. 
    Goode B, Mondal G, Hyun M, Ruiz DG, Lin YH et al. 2018. A recurrent kinase domain mutation in PRKCA defines chordoid glioma of the third ventricle. Nat. Commun. 9:810
    [Google Scholar]
  30. 30. 
    Greer A, Foreman NK, Donson A, Davies KD, Kleinschmidt-DeMasters BK 2017. Desmoplastic infantile astrocytoma/ganglioglioma with rare BRAF V600D mutation. Pediatr. Blood Cancer 64: https://doi.org/10.1002/pbc.26350
    [Crossref] [Google Scholar]
  31. 31. 
    Grobner SN, Worst BC, Weischenfeldt J, Buchhalter I, Kleinheinz K et al. 2018. The landscape of genomic alterations across childhood cancers. Nature 555:321–27
    [Google Scholar]
  32. 32. 
    Grondin RT, Scott RM, Smith ER 2009. Pediatric brain tumors. Adv. Pediatr. 56:249–69
    [Google Scholar]
  33. 33. 
    Hong DS, Bauer TM, Lee JJ, Dowlati A, Brose MS et al. 2019. Larotrectinib in adult patients with solid tumours: a multi-centre, open-label, phase I dose-escalation study. Ann. Oncol. 30:325–31
    [Google Scholar]
  34. 34. 
    Hou Y, Pinheiro J, Sahm F, Reuss DE, Schrimpf D et al. 2019. Papillary glioneuronal tumor (PGNT) exhibits a characteristic methylation profile and fusions involving PRKCA. Acta Neuropathol 137:837–46
    [Google Scholar]
  35. 35. 
    Huse JT, Snuderl M, Jones DTW, Brathwaite CD, Altman N et al. 2017. Polymorphous low-grade neuroepithelial tumor of the young (PLNTY): an epileptogenic neoplasm with oligodendroglioma-like components, aberrant CD34 expression, and genetic alterations involving the MAP kinase pathway. Acta Neuropathol 133:417–29
    [Google Scholar]
  36. 36. 
    Jacob K, Albrecht S, Sollier C, Faury D, Sader E 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]
  37. 37. 
    Jacob K, Quang-Khuong DA, Jones DTW, Witt H, Lambert S et al. 2011. Genetic aberrations leading to MAPK pathway activation mediate oncogene-induced senescence in sporadic pilocytic astrocytomas. Clin. Cancer Res. 17:4650–60
    [Google Scholar]
  38. 38. 
    Jiao Y, Killela PJ, Reitman ZJ, Rasheed AB, Heaphy CM et al. 2012. Frequent ATRX, CIC, FUBP1 and IDH1 mutations refine the classification of malignant gliomas. Oncotarget 3:709–22
    [Google Scholar]
  39. 39. 
    Jones C, Karajannis MA, Jones DTW, Kieran MW, Monje M et al. 2017. Pediatric high-grade glioma: biologically and clinically in need of new thinking. Neuro-Oncology 19:153–61
    [Google Scholar]
  40. 40. 
    Jones DTW, Hutter B, Jäger N, Korshunov A, Kool M et al. 2013. Recurrent somatic alterations of FGFR1 and NTRK2 in pilocytic astrocytoma. Nat. Genet. 45:927–32
    [Google Scholar]
  41. 41. 
    Jones DTW, Ichimura K, Liu L, Pearson DM, Plant K, Collins VP 2006. Genomic analysis of pilocytic astrocytomas at 0.97 Mb resolution shows an increasing tendency toward chromosomal copy number change with age. J. Neuropathol. Exp. Neurol. 65:1049–58
    [Google Scholar]
  42. 42. 
    Jones DTW, Kocialkowski S, Liu L, Pearson DM, Backlund LM et al. 2008. Tandem duplication producing a novel oncogenic BRAF fusion gene defines the majority of pilocytic astrocytomas. Cancer Res 68:8673–77
    [Google Scholar]
  43. 43. 
    Jones DTW, Kocialkowski S, Liu L, Pearson DM, Ichimura K, Collins VP 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]
  44. 44. 
    Jones DTW, Witt O, Pfister SM 2018. BRAF V600E status alone is not sufficient as a prognostic biomarker in pediatric low-grade glioma. J. Clin. Oncol. 36:96
    [Google Scholar]
  45. 45. 
    Karajannis MA, Legault G, Hagiwara M, Giancotti FG, Filatov A et al. 2014. Phase II study of everolimus in children and adults with neurofibromatosis type 2 and progressive vestibular schwannomas. Neuro-Oncology 16:292–97
    [Google Scholar]
  46. 46. 
    Khater F, Langlois S, Cassart P, Roy A-M, Lajoie M et al. 2019. Recurrent somatic BRAF insertion (p.V504_R506dup): a tumor marker and a potential therapeutic target in pilocytic astrocytoma. Oncogene 38:2994–3002
    [Google Scholar]
  47. 47. 
    Kieran MW, Bouffet E, Broniscer A, Cohen KJ, Geoerger B et al. 2018. Efficacy and safety results from a phase I/IIa study of dabrafenib in pediatric patients with BRAFV600-mutant relapsed refractory low-grade glioma. J. Clin. Oncol. 36:10506
    [Google Scholar]
  48. 48. 
    Kieran MW, Walker D, Frappaz D, Prados M 2010. Brain tumors: from childhood through adolescence into adulthood. J. Clin. Oncol. 28:4783–89
    [Google Scholar]
  49. 49. 
    Kondyli M, Larouche V, Saint-Martin C, Ellezam B, Pouliot L et al. 2018. Trametinib for progressive pediatric low-grade gliomas. J. Neuro-Oncology 140:435–44
    [Google Scholar]
  50. 50. 
    Kopinja J, Sevilla RS, Levitan D, Dai D, Vanko A et al. 2017. A brain penetrant mutant IDH1 inhibitor provides in vivo survival benefit. Sci. Rep. 7:13853
    [Google Scholar]
  51. 51. 
    Korshunov A, Chavez L, Sharma T, Ryzhova M, Schrimpf D et al. 2018. Epithelioid glioblastomas stratify into established diagnostic subsets upon integrated molecular analysis. Brain Pathol 28:656–62
    [Google Scholar]
  52. 52. 
    Krishnatry R, Zhukova N, Guerreiro Stucklin AS, Pole JD, Mistry M et al. 2016. Clinical and treatment factors determining long-term outcomes for adult survivors of childhood low-grade glioma: a population-based study. Cancer 122:1261–69
    [Google Scholar]
  53. 53. 
    Lai A, Kharbanda S, Pope WB, Tran A, Solis OE et al. 2011. Evidence for sequenced molecular evolution of IDH1 mutant glioblastoma from a distinct cell of origin. J. Clin. Oncol. 29:4482–90
    [Google Scholar]
  54. 54. 
    Lassaletta A, Zapotocky M, Mistry M, Ramaswamy V, Honnorat M et al. 2017. Therapeutic and prognostic implications of BRAF V600E in pediatric low-grade gliomas. J. Clin. Oncol. 35:2934–41
    [Google Scholar]
  55. 55. 
    Lawrence MS, Stojanov P, Mermel CH, Robinson JT, Garraway LA et al. 2014. Discovery and saturation analysis of cancer genes across 21 tumour types. Nature 505:495–501
    [Google Scholar]
  56. 56. 
    Li X, Newbern JM, Wu Y, Morgan-Smith M, Zhong J et al. 2012. MEK is a key regulator of gliogenesis in the developing brain. Neuron 75:1035–50
    [Google Scholar]
  57. 57. 
    Liu XY, Gerges N, Korshunov A, Sabha N, Khuong-Quang DA 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]
  58. 58. 
    Louis DN, Ohgaki H, Wiestler OD, Cavenee WK, Burger PC et al. 2007. The 2007 WHO classification of tumours of the central nervous system. Acta Neuropathol 114:97–109
    [Google Scholar]
  59. 59. 
    Louis DN, Ohgaki H, Wiestler OD, Cavenee WK, Ellison DW et al. 2016. WHO Classification of Tumours of the Central Nervous System, Revised. Fourth Edition Lyon, France: IARC408 pp.
  60. 60. 
    Louis DN, Perry A, Reifenberger G, von Deimling A, Figarella-Branger D et al. 2016. The 2016 World Health Organization classification of tumors of the central nervous system: a summary. Acta Neuropathol 131:803–20
    [Google Scholar]
  61. 61. 
    Lovely MP, Stewart-Amidei C, Page M, Mogensen K, Arzbaecher J et al. 2013. A new reality: long-term survivorship with a malignant brain tumor. Oncol. Nurs. Forum 40:267–74
    [Google Scholar]
  62. 62. 
    Mistry M, Zhukova N, Merico D, Rakopoulos P, Krishnatry R et al. 2015. BRAF mutation and CDKN2A deletion define a clinically distinct subgroup of childhood secondary high-grade glioma. J. Clin. Oncol. 33:1015–22
    [Google Scholar]
  63. 63. 
    Nguyen AT, Colin C, Nanni-Metellus I, Padovani L, Maurage C-A et al. 2015. Evidence for BRAF V600E and H3F3A K27M double mutations in paediatric glial and glioneuronal tumours. Neuropathol. Appl. Neurobiol. 41:403–8
    [Google Scholar]
  64. 64. 
    Norsworthy KJ, Luo L, Hsu V, Gudi R, Dorff SE et al. 2019. FDA Approval Summary: ivosidenib for relapsed or refractory acute myeloid leukemia with an isocitrate dehydrogenase-1 mutation. Clin. Cancer Res. 25:3205–9
    [Google Scholar]
  65. 65. 
    Northcott PA, Buchhalter I, Morrissy AS, Hovestadt V, Weischenfeldt J et al. 2017. The whole-genome landscape of medulloblastoma subtypes. Nature 547:311–17
    [Google Scholar]
  66. 66. 
    Ostrom QT, Gittleman H, Fulop J, Liu M, Blanda R et al. 2015. CBTRUS Statistical Report: primary brain and central nervous system tumors diagnosed in the United States in 2008–2012. Neuro-Oncology 17:Suppl. 4iv1–62
    [Google Scholar]
  67. 67. 
    Packer RJ, Pfister S, Bouffet E, Avery R, Bandopadhayay P et al. 2017. Pediatric low-grade gliomas: implications of the biologic era. Neuro-Oncology 19:750–61
    [Google Scholar]
  68. 68. 
    Pagès M, Beccaria K, Boddaert N, Saffroy R, Besnard A et al. 2018. Co-occurrence of histone H3 K27M and BRAF V600E mutations in paediatric midline grade I ganglioglioma. Brain Pathol 28:103–11
    [Google Scholar]
  69. 69. 
    Pajtler KW, Witt H, Sill M, Jones DTW, Hovestadt V et al. 2015. Molecular classification of ependymal tumors across all CNS compartments, histopathological grades, and age groups. Cancer Cell 27:728–43
    [Google Scholar]
  70. 70. 
    Parsons DW, Jones S, Zhang X, Lin JC, Leary RJ et al. 2008. An integrated genomic analysis of human glioblastoma multiforme. Science 321:1807–12
    [Google Scholar]
  71. 71. 
    Pfister S, Janzarik WG, Remke M, Ernst A, Werft W 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]
  72. 72. 
    Pollack IF. 1999. Pediatric brain tumors. Semin. Surg. Oncol. 16:73–90
    [Google Scholar]
  73. 73. 
    Preuss M, Christiansen H, Merkenschlager A, Hirsch FW, Kiess W et al. 2015. Disseminated oligodendroglial-like leptomeningeal tumors: preliminary diagnostic and therapeutic results for a novel tumor entity [corrected]. J. Neurooncol. 124:65–74
    [Google Scholar]
  74. 74. 
    Pusch S, Krausert S, Fischer V, Balss J, Ott M et al. 2017. Pan-mutant IDH1 inhibitor BAY 1436032 for effective treatment of IDH1 mutant astrocytoma in vivo. Acta Neuropathol 133:629–44
    [Google Scholar]
  75. 75. 
    Qaddoumi I, Orisme W, Wen J, Santiago T, Gupta K et al. 2016. Genetic alterations in uncommon low-grade neuroepithelial tumors: BRAF, FGFR1, and MYB mutations occur at high frequency and align with morphology. Acta Neuropathol 131:833–45
    [Google Scholar]
  76. 76. 
    Ramkissoon LA, Horowitz PM, Craig JM, Ramkissoon SH, Rich BE 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]
  77. 77. 
    Reinhardt A, Stichel D, Schrimpf D, Sahm F, Korshunov A et al. 2018. Anaplastic astrocytoma with piloid features, a novel molecular class of IDH wildtype glioma with recurrent MAPK pathway, CDKN2A/B and ATRX alterations. Acta Neuropathol 136:273–91
    [Google Scholar]
  78. 78. 
    Rivera B, Gayden T, Carrot-Zhang J, Nadaf J, Boshari T et al. 2016. Germline and somatic FGFR1 abnormalities in dysembryoplastic neuroepithelial tumors. Acta Neuropathol 131:847–63
    [Google Scholar]
  79. 79. 
    Rodriguez FJ, Perry A, Rosenblum MK, Krawitz S, Cohen KJ et al. 2012. Disseminated oligodendroglial-like leptomeningeal tumor of childhood: a distinctive clinicopathologic entity. Acta Neuropathol 124:627–41
    [Google Scholar]
  80. 80. 
    Roessmann U, Gambetti P. 1986. Astrocytes in the developing human brain. An immunohistochemical study. Acta Neuropathol 70:308–13
    [Google Scholar]
  81. 81. 
    Rush S, Foreman N, Liu A 2013. Brainstem ganglioglioma successfully treated with vemurafenib. J. Clin. Oncol. 31:e159–60
    [Google Scholar]
  82. 82. 
    Ryall S, Krishnatry R, Arnoldo A, Buczkowicz P, Mistry M et al. 2016. Targeted detection of genetic alterations reveal the prognostic impact of H3K27M and MAPK pathway aberrations in paediatric thalamic glioma. Acta Neuropathol. Commun. 4:93
    [Google Scholar]
  83. 83. 
    Sanford RA, Bowman R, Tomita T, De Leon G, Palka P 1999. A 16-year-old male with Noonan's syndrome develops progressive scoliosis and deteriorating gait. Pediatr. Neurosurg. 30:47–52
    [Google Scholar]
  84. 84. 
    Scheithauer BW, Silva AI, Ketterling RP, Pula JH, Lininger JF, Krinock MJ 2009. Rosette-forming glioneuronal tumor: report of a chiasmal-optic nerve example in neurofibromatosis type 1: special pathology report. Neurosurgery 64:E771–72
    [Google Scholar]
  85. 85. 
    Schindler G, Capper D, Meyer J, Janzarik W, Omran H et al. 2011. Analysis of BRAF V600E mutation in 1,320 nervous system tumors reveals high mutation frequencies in pleomorphic xanthoastrocytoma, ganglioglioma and extra-cerebellar pilocytic astrocytoma. Acta Neuropathol 121:397–405
    [Google Scholar]
  86. 86. 
    Schuettpelz LG, McDonald S, Whitesell K, Desruisseau DM, Grange DK et al. 2009. Pilocytic astrocytoma in a child with Noonan syndrome. Pediatr. Blood Cancer 53:1147–49
    [Google Scholar]
  87. 87. 
    Schwartzentruber J, Korshunov A, Liu XY, Jones DTW, Pfaff E et al. 2012. Driver mutations in histone H3.3 and chromatin remodelling genes in paediatric glioblastoma. Nature 482:226–31
    [Google Scholar]
  88. 88. 
    Semple BD, Blomgren K, Gimlin K, Ferriero DM, Noble-Haeusslein LJ 2013. Brain development in rodents and humans: identifying benchmarks of maturation and vulnerability to injury across species. Prog. Neurobiol. 106–7:1–16
    [Google Scholar]
  89. 89. 
    Sievers P, Appay R, Schrimpf D, Stichel D, Reuss DE et al. 2019. Rosette-forming glioneuronal tumors share a distinct DNA methylation profile and mutations in FGFR1, with recurrent co-mutation of PIK3CA and NF1. Acta Neuropathol 138:497–504
    [Google Scholar]
  90. 90. 
    Sievers P, Stichel D, Schrimpf D, Sahm F, Koelsche C et al. 2018. FGFR1:TACC1 fusion is a frequent event in molecularly defined extraventricular neurocytoma. Acta Neuropathol 136:293–302
    [Google Scholar]
  91. 91. 
    Sievert AJ, Lang SS, Boucher KL, Madsen PJ, Slaunwhite E et al. 2013. Paradoxical activation and RAF inhibitor resistance of BRAF protein kinase fusions characterizing pediatric astrocytomas. PNAS 110:5957–62
    [Google Scholar]
  92. 92. 
    Singh D, Chan JM, Zoppoli P, Niola F, Sullivan R et al. 2012. Transforming fusions of FGFR and TACC genes in human glioblastoma. Science 337:1231–35
    [Google Scholar]
  93. 93. 
    Solomon DA, Korshunov A, Sill M, Jones DTW, Kool M et al. 2018. Myxoid glioneuronal tumor of the septum pellucidum and lateral ventricle is defined by a recurrent PDGFRA p.K385 mutation and DNT-like methylation profile. Acta Neuropathol 136:339–43
    [Google Scholar]
  94. 94. 
    Sturm D, Bender S, Jones DTW, Lichter P, Grill J et al. 2014. Paediatric and adult glioblastoma: Multiform (epi)genomic culprits emerge. Nat. Rev. Cancer 14:92–107
    [Google Scholar]
  95. 95. 
    Suzuki H, Aoki K, Chiba K, Sato Y, Shiozawa Y et al. 2015. Mutational landscape and clonal architecture in grade II and III gliomas. Nat. Genet. 47:458–68
    [Google Scholar]
  96. 96. 
    Tatevossian RG, Tang B, Dalton J, Forshew T, Lawson AR et al. 2010. MYB upregulation and genetic aberrations in a subset of pediatric low-grade gliomas. Acta Neuropathol 120:731–43
    [Google Scholar]
  97. 97. 
    Taylor MD, Northcott PA, Korshunov A, Remke M, Cho YJ et al. 2012. Molecular subgroups of medulloblastoma: the current consensus. Acta Neuropathol 123:465–72
    [Google Scholar]
  98. 98. 
    Valera ET, McConechy MK, Gayden T, Rivera B, Jones DTW et al. 2018. Methylome analysis and whole-exome sequencing reveal that brain tumors associated with encephalocraniocutaneous lipomatosis are midline pilocytic astrocytomas. Acta Neuropathol 136:657–60
    [Google Scholar]
  99. 99. 
    van den Bent MJ. 2010. Interobserver variation of the histopathological diagnosis in clinical trials on glioma: a clinician's perspective. Acta Neuropathol 120:297–304
    [Google Scholar]
  100. 100. 
    Weber RG, Hoischen A, Ehrler M, Zipper P, Kaulich K et al. 2007. Frequent loss of chromosome 9, homozygous CDKN2A/p14ARF/CDKN2B deletion and low TSC1 mRNA expression in pleomorphic xanthoastrocytomas. Oncogene 26:1088–97
    [Google Scholar]
  101. 101. 
    Wu G, Diaz AK, Paugh BS, Rankin SL, Ju B 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]
  102. 102. 
    Yan H, Parsons DW, Jin G, McLendon R, Rasheed BA et al. 2009. IDH1 and IDH2 mutations in gliomas. New Engl. J. Med. 360:765–73
    [Google Scholar]
  103. 103. 
    Zhang J, Wu G, Miller CP, Tatevossian RG, Dalton JD et al. 2013. Whole-genome sequencing identifies genetic alterations in pediatric low-grade gliomas. Nat. Genet. 45:602–12
    [Google Scholar]
/content/journals/10.1146/annurev-genet-120417-031642
Loading
/content/journals/10.1146/annurev-genet-120417-031642
Loading

Data & Media loading...

  • Article Type: Review Article
This is a required field
Please enter a valid email address
Approval was a Success
Invalid data
An Error Occurred
Approval was partially successful, following selected items could not be processed due to error