Skip to main content

Molecular Testing in CNS tumors

  • Chapter
Molecular Testing in Cancer
  • 1716 Accesses

Abstract

This chapter reviews the molecular alterations of the most common tumors of the central nervous system. Relevant molecular tests with proven clinical utility will also be reviewed. The chapter begins with a discussion of the most recent significant advances in molecular neuro-oncology with regard to diagnosis, prognosis, and treatment selection.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 89.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 119.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 169.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

References

  1. Louis DN. The next step in brain tumor classification: “Let us now praise famous men”… or molecules? Acta Neuropathol. 2012;124:761–2.

    Article  PubMed  PubMed Central  Google Scholar 

  2. Weller M, Stupp R, Hegi ME, van den Bent M, Tonn JC, Sanson M, et al. Personalized care in neuro-oncology coming of age: why we need MGMT and 1p/19q testing for malignant glioma patients in clinical practice. Neuro Oncol. 2012;14 Suppl 4:iv100–8.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  3. Parsons DW, Jones S, Zhang X, Lin JC, Leary RJ, Angenendt P, et al. An integrated genomic analysis of human glioblastoma multiforme. Science. 2008;321:1807–12.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  4. Yan H, Parsons DW, Jin G, McLendon R, Rasheed BA, Yuan W, et al. IDH1 and IDH2 mutations in gliomas. N Engl J Med. 2009;360:765–73.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  5. Houillier C, Wang X, Kaloshi G, Mokhtari K, Guillevin R, Laffaire J, et al. IDH1 or IDH2 mutations predict longer survival and response to temozolomide in low-grade gliomas. Neurology. 2010;75:1560–6.

    Article  CAS  PubMed  Google Scholar 

  6. Antonelli M, Buttarelli FR, Arcella A, Nobusawa S, Donofrio V, Oghaki H, et al. Prognostic significance of histological grading, p53 status, YKL-40 expression, and IDH1 mutations in pediatric high-grade gliomas. J Neuro-Oncol. 2010;99:209–15.

    Article  CAS  Google Scholar 

  7. Paugh BS, Qu C, Jones C, Liu Z, Adamowicz-Brice M, Zhang J, et al. Integrated molecular genetic profiling of pediatric high-grade gliomas reveals key differences with the adult disease. J Clin Oncol. 2010;28:3061–8.

    Article  PubMed  PubMed Central  Google Scholar 

  8. Capper D, Sahm F, Hartmann C, Meyermann R, von Deimling A, Schittenhelm J. Application of mutant IDH1 antibody to differentiate diffuse glioma from nonneoplastic central nervous system lesions and therapy-induced changes. Am J Surg Pathol. 2010;34:1199–204.

    Article  PubMed  Google Scholar 

  9. Capper D, Weissert S, Balss J, Habel A, Meyer J, Jager D, et al. Characterization of R132H mutation-specific IDH1 antibody binding in brain tumors. Brain Pathol. 2010;20:245–54.

    Article  CAS  PubMed  Google Scholar 

  10. Capper D, Zentgraf H, Balss J, Hartmann C, von Deimling A. Monoclonal antibody specific for IDH1 R132H mutation. Acta Neuropathol. 2009;118:599–601.

    Article  CAS  PubMed  Google Scholar 

  11. Esteller M, Garcia-Foncillas J, Andion E, Goodman SN, Hidalgo OF, Vanaclocha V, et al. Inactivation of the DNA-repair gene MGMT and the clinical response of gliomas to alkylating agents. N Engl J Med. 2000;343:1350–4.

    Article  CAS  PubMed  Google Scholar 

  12. Hegi ME, Diserens AC, Gorlia T, Hamou MF, de Tribolet N, Weller M, et al. MGMT gene silencing and benefit from temozolomide in glioblastoma. N Engl J Med. 2005;352:997–1003.

    Article  CAS  PubMed  Google Scholar 

  13. Wick W, Platten M, Meisner C, Felsberg J, Tabatabai G, Simon M, et al. Temozolomide chemotherapy alone versus radiotherapy alone for malignant astrocytoma in the elderly: the NOA-08 randomised, phase 3 trial. Lancet Oncol. 2012;13:707–15.

    Article  CAS  PubMed  Google Scholar 

  14. Malmstrom A, Gronberg BH, Marosi C, Stupp R, Frappaz D, Schultz H, et al. Temozolomide versus standard 6-week radiotherapy versus hypofractionated radiotherapy in patients older than 60 years with glioblastoma: the Nordic randomised, phase 3 trial. Lancet Oncol. 2012;13:916–26.

    Article  PubMed  Google Scholar 

  15. Mikeska T, Bock C, El-Maarri O, Hubner A, Ehrentraut D, Schramm J, et al. Optimization of quantitative MGMT promoter methylation analysis using pyrosequencing and combined bisulfite restriction analysis. J Mol Diagn. 2007;9:368–81.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  16. Mason S, McDonald K. MGMT testing for glioma in clinical laboratories: discordance with methylation analyses prevents the implementation of routine immunohistochemistry. J Cancer Res Clin Oncol. 2012;138:1789–97.

    Article  CAS  PubMed  Google Scholar 

  17. Preusser M, Elezi L, Hainfellner JA. Reliability and reproducibility of PCR-based testing of O6-methylguanine-DNA methyltransferase gene (MGMT) promoter methylation status in formalin-fixed and paraffin-embedded neurosurgical biopsy specimens. Clin Neuropathol. 2008;27:388–90.

    Article  CAS  PubMed  Google Scholar 

  18. Quillien V, Lavenu A, Karayan-Tapon L, Carpentier C, Labussiere M, Lesimple T, et al. Comparative assessment of 5 methods (methylation-specific polymerase chain reaction, MethyLight, pyrosequencing, methylation-sensitive high-resolution melting, and immunohistochemistry) to analyze O6-methylguanine-DNA-methyltranferase in a series of 100 glioblastoma patients. Cancer. 2012;118:4201–11.

    Article  CAS  PubMed  Google Scholar 

  19. Eads CA, Danenberg KD, Kawakami K, Saltz LB, Blake C, Shibata D, et al. MethyLight: a high-throughput assay to measure DNA methylation. Nucleic Acids Res. 2000;28:E32.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  20. Vlassenbroeck I, Califice S, Diserens AC, Migliavacca E, Straub J, Di Stefano I, et al. Validation of real-time methylation-specific PCR to determine O6-methylguanine-DNA methyltransferase gene promoter methylation in glioma. J Mol Diagn. 2008;10:332–7.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  21. Jeuken JW, Cornelissen SJ, Vriezen M, Dekkers MM, Errami A, Sijben A, et al. MS-MLPA: an attractive alternative laboratory assay for robust, reliable, and semiquantitative detection of MGMT promoter hypermethylation in gliomas. Lab Invest. 2007;87:1055–65.

    Article  CAS  PubMed  Google Scholar 

  22. Bady P, Sciuscio D, Diserens AC, Bloch J, van den Bent MJ, Marosi C, et al. MGMT methylation analysis of glioblastoma on the Infinium methylation BeadChip identifies two distinct CpG regions associated with gene silencing and outcome, yielding a prediction model for comparisons across datasets, tumor grades, and CIMP-status. Acta Neuropathol. 2012;124:547–60.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  23. Hsu CY, Lin SC, Ho HL, Chang-Chien YC, Hsu SP, Yen YS, et al. Exclusion of histiocytes/endothelial cells and using endothelial cells as internal reference are crucial for interpretation of MGMT immunohistochemistry in glioblastoma. Am J Surg Pathol. 2013;37:264–71.

    Article  PubMed  Google Scholar 

  24. Louis DN, Gusella JF. A tiger behind many doors: multiple genetic pathways to malignant glioma. Trends Genet. 1995;11:412–5.

    Article  CAS  PubMed  Google Scholar 

  25. Reifenberger J, Reifenberger G, Liu L, James CD, Wechsler W, Collins VP. Molecular genetic analysis of oligodendroglial tumors shows preferential allelic deletions on 19q and 1p. Am J Pathol. 1994;145:1175–90.

    CAS  PubMed  PubMed Central  Google Scholar 

  26. von Deimling A, Louis DN, von Ammon K, Petersen I, Wiestler OD, Seizinger BR. Evidence for a tumor suppressor gene on chromosome 19q associated with human astrocytomas, oligodendrogliomas, and mixed gliomas. Cancer Res. 1992;52:4277–9.

    Google Scholar 

  27. Griffin CA, Burger P, Morsberger L, Yonescu R, Swierczynski S, Weingart JD, et al. Identification of der(1;19)(q10;p10) in five oligodendrogliomas suggests mechanism of concurrent 1p and 19q loss. J Neuropathol Exp Neurol. 2006;65:988–94.

    Article  PubMed  Google Scholar 

  28. Bettegowda C, Agrawal N, Jiao Y, Sausen M, Wood LD, Hruban RH, et al. Mutations in CIC and FUBP1 contribute to human oligodendroglioma. Science. 2011;333:1453–5.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  29. Sahm F, Koelsche C, Meyer J, Pusch S, Lindenberg K, Mueller W, et al. CIC and FUBP1 mutations in oligodendrogliomas, oligoastrocytomas and astrocytomas. Acta Neuropathol. 2012;123:853–60.

    Article  CAS  PubMed  Google Scholar 

  30. Labussiere M, Idbaih A, Wang XW, Marie Y, Boisselier B, Falet C, et al. All the 1p19q codeleted gliomas are mutated on IDH1 or IDH2. Neurology. 2010;74:1886–90.

    Article  CAS  PubMed  Google Scholar 

  31. Cairncross JG, Ueki K, Zlatescu MC, Lisle DK, Finkelstein DM, Hammond RR, et al. Specific genetic predictors of chemotherapeutic response and survival in patients with anaplastic oligodendrogliomas. J Natl Cancer Inst. 1998;90:1473–9.

    Article  CAS  PubMed  Google Scholar 

  32. Kouwenhoven MC, Gorlia T, Kros JM, Ibdaih A, Brandes AA, Bromberg JE, et al. Molecular analysis of anaplastic oligodendroglial tumors in a prospective randomized study: a report from EORTC study 26951. Neuro Oncol. 2009;11:737–46.

    Article  PubMed  PubMed Central  Google Scholar 

  33. Woehrer A, Sander P, Haberler C, Kern S, Maier H, Preusser M, et al. FISH-based detection of 1p 19q codeletion in oligodendroglial tumors: procedures and protocols for neuropathological practice—a publication under the auspices of the Research Committee of the European Confederation of Neuropathological Societies (Euro-CNS). Clin Neuropathol. 2011;30:47–55.

    Article  CAS  PubMed  Google Scholar 

  34. Smith JS, Alderete B, Minn Y, Borell TJ, Perry A, Mohapatra G, et al. Localization of common deletion regions on 1p and 19q in human gliomas and their association with histological subtype. Oncogene. 1999;18:4144–52.

    Article  CAS  PubMed  Google Scholar 

  35. Reddy KS. Assessment of 1p/19q deletions by fluorescence in situ hybridization in gliomas. Cancer Genet Cytogenet. 2008;184:77–86.

    Article  CAS  PubMed  Google Scholar 

  36. Hatanpaa KJ, Burger PC, Eshleman JR, Murphy KM, Berg KD. Molecular diagnosis of oligodendroglioma in paraffin sections. Lab Invest. 2003;83:419–28.

    Article  CAS  PubMed  Google Scholar 

  37. Nigro JM, Takahashi MA, Ginzinger DG, Law M, Passe S, Jenkins RB, et al. Detection of 1p and 19q loss in oligodendroglioma by quantitative microsatellite analysis, a real-time quantitative polymerase chain reaction assay. Am J Pathol. 2001;158:1253–62.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  38. Kros JM, van Run PR, Alers JC, Beverloo HB, van den Bent MJ, Avezaat CJ, et al. Genetic aberrations in oligodendroglial tumours: an analysis using comparative genomic hybridization (CGH). J Pathol. 1999;188:282–8.

    Article  CAS  PubMed  Google Scholar 

  39. Burger PC, Minn AY, Smith JS, Borell TJ, Jedlicka AE, Huntley BK, et al. Losses of chromosomal arms 1p and 19q in the diagnosis of oligodendroglioma. A study of paraffin-embedded sections. Mod Pathol. 2001;14:842–53.

    Article  CAS  PubMed  Google Scholar 

  40. Natte R, van Eijk R, Eilers P, Cleton-Jansen AM, Oosting J, Kouwenhove M, et al. Multiplex ligation-dependent probe amplification for the detection of 1p and 19q chromosomal loss in oligodendroglial tumors. Brain Pathol. 2005;15:192–7.

    Article  CAS  PubMed  Google Scholar 

  41. Bengtsson H, Wirapati P, Speed TP. A single-array preprocessing method for estimating full-resolution raw copy numbers from all Affymetrix genotyping arrays including GenomeWideSNP 5 & 6. Bioinformatics. 2009;25:2149–56.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  42. Xie C, Tammi MT. CNV-seq, a new method to detect copy number variation using high-throughput sequencing. BMC Bioinformatics. 2009;10:80.

    Article  PubMed  PubMed Central  Google Scholar 

  43. Schindler G, Capper D, Meyer J, Janzarik W, Omran H, Herold-Mende C, et al. 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. 2011;121:397–405.

    Article  CAS  PubMed  Google Scholar 

  44. Schiffman JD, Hodgson JG, VandenBerg SR, Flaherty P, Polley MY, Yu M, et al. Oncogenic BRAF mutation with CDKN2A inactivation is characteristic of a subset of pediatric malignant astrocytomas. Cancer Res. 2010;70:512–9.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  45. Louis DN. International Agency for Research on Cancer, World Health Organization. WHO classification of tumours of the central nervous system. 4th ed. Lyon: International Agency for Research on Cancer; 2007.

    Google Scholar 

  46. Perry A, Giannini C, Scheithauer BW, Rojiani AM, Yachnis AT, Seo IS, et al. Composite pleomorphic xanthoastrocytoma and ganglioglioma: report of four cases and review of the literature. Am J Surg Pathol. 1997;21:763–71.

    Article  CAS  PubMed  Google Scholar 

  47. Capper D, Preusser M, Habel A, Sahm F, Ackermann U, Schindler G, et al. Assessment of BRAF V600E mutation status by immunohistochemistry with a mutation-specific monoclonal antibody. Acta Neuropathol. 2011;122:11–9.

    Article  CAS  PubMed  Google Scholar 

  48. Capper D, Berghoff AS, Magerle M, Ilhan A, Wohrer A, Hackl M, et al. Immunohistochemical testing of BRAF V600E status in 1,120 tumor tissue samples of patients with brain metastases. Acta Neuropathol. 2012;123:223–33.

    Article  CAS  PubMed  Google Scholar 

  49. Horbinski C. To BRAF or not to BRAF: is that even a question anymore? J Neuropathol Exp Neurol. 2013;72:2–7.

    Article  PubMed  PubMed Central  Google Scholar 

  50. Sanoudou D, Tingby O, Ferguson-Smith MA, Collins VP, Coleman N. Analysis of pilocytic astrocytoma by comparative genomic hybridization. Br J Cancer. 2000;82:1218–22.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  51. Bar EE, Lin A, Tihan T, Burger PC, Eberhart CG. Frequent gains at chromosome 7q34 involving BRAF in pilocytic astrocytoma. J Neuropathol Exp Neurol. 2008;67:878–87.

    Article  CAS  PubMed  Google Scholar 

  52. Jones DT, Kocialkowski S, Liu L, Pearson DM, Backlund LM, Ichimura K, et al. Tandem duplication producing a novel oncogenic BRAF fusion gene defines the majority of pilocytic astrocytomas. Cancer Res. 2008;68:8673–7.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  53. Forshew T, Tatevossian RG, Lawson AR, Ma J, Neale G, Ogunkolade BW, et al. Activation of the ERK/MAPK pathway: a signature genetic defect in posterior fossa pilocytic astrocytomas. J Pathol. 2009;218:172–81.

    Article  CAS  PubMed  Google Scholar 

  54. Horbinski C, Hamilton RL, Nikiforov Y, Pollack IF. Association of molecular alterations, including BRAF, with biology and outcome in pilocytic astrocytomas. Acta Neuropathol. 2010;119:641–9.

    Article  CAS  PubMed  Google Scholar 

  55. Korshunov A, Meyer J, Capper D, Christians A, Remke M, Witt H, et al. Combined molecular analysis of BRAF and IDH1 distinguishes pilocytic astrocytoma from diffuse astrocytoma. Acta Neuropathol. 2009;118:401–5.

    Article  CAS  PubMed  Google Scholar 

  56. Tian Y, Rich BE, Vena N, Craig JM, Macconaill LE, Rajaram V, et al. Detection of KIAA1549-BRAF fusion transcripts in formalin-fixed paraffin-embedded pediatric low-grade gliomas. J Mol Diagn. 2011;13:669–77.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  57. Ohgaki H, Dessen P, Jourde B, Horstmann S, Nishikawa T, Di Patre PL, et al. Genetic pathways to glioblastoma: a population-based study. Cancer Res. 2004;64:6892–9.

    Article  CAS  PubMed  Google Scholar 

  58. Watanabe K, Tachibana O, Sata K, Yonekawa Y, Kleihues P, Ohgaki H. Overexpression of the EGF receptor and p53 mutations are mutually exclusive in the evolution of primary and secondary glioblastomas. Brain Pathol. 1996;6:217–23; discussion 23–4.

    Google Scholar 

  59. Burger PC, Pearl DK, Aldape K, Yates AJ, Scheithauer BW, Passe SM, et al. Small cell architecture—a histological equivalent of EGFR amplification in glioblastoma multiforme? J Neuropathol Exp Neurol. 2001;60:1099–104.

    Article  CAS  PubMed  Google Scholar 

  60. Gaiser T, Waha A, Moessler F, Bruckner T, Pietsch T, von Deimling A. Comparison of automated silver enhanced in situ hybridization and fluorescence in situ hybridization for evaluation of epidermal growth factor receptor status in human glioblastomas. Mod Pathol. 2009;22:1263–71.

    Article  CAS  PubMed  Google Scholar 

  61. Kuan CT, Wikstrand CJ, Bigner DD. EGFRvIII as a promising target for antibody-based brain tumor therapy. Brain Tumor Pathol. 2000;17:71–8.

    Article  CAS  PubMed  Google Scholar 

  62. Wikstrand CJ, Hale LP, Batra SK, Hill ML, Humphrey PA, Kurpad SN, et al. Monoclonal antibodies against EGFRvIII are tumor specific and react with breast and lung carcinomas and malignant gliomas. Cancer Res. 1995;55:3140–8.

    CAS  PubMed  Google Scholar 

  63. Moscatello DK, Ramirez G, Wong AJ. A naturally occurring mutant human epidermal growth factor receptor as a target for peptide vaccine immunotherapy of tumors. Cancer Res. 1997;57:1419–24.

    CAS  PubMed  Google Scholar 

  64. Li G, Mitra S, Wong AJ. The epidermal growth factor variant III peptide vaccine for treatment of malignant gliomas. Neurosurg Clin N Am. 2010;21:87–93.

    Article  PubMed  Google Scholar 

  65. Gupta P, Han SY, Holgado-Madruga M, Mitra SS, Li G, Nitta RT, et al. Development of an EGFRvIII specific recombinant antibody. BMC Biotechnol. 2010;10:72.

    Article  PubMed  PubMed Central  Google Scholar 

  66. Ohgaki H, Kleihues P. Genetic pathways to primary and secondary glioblastoma. Am J Pathol. 2007;170:1445–53.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  67. Adams EJ, Green JA, Clark AH, Youngson JH. Comparison of different scoring systems for immunohistochemical staining. J Clin Pathol. 1999;52:75–7.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  68. Zlobec I, Steele R, Michel RP, Compton CC, Lugli A, Jass JR. Scoring of p53, VEGF, Bcl-2 and APAF-1 immunohistochemistry and interobserver reliability in colorectal cancer. Mod Pathol. 2006;19:1236–42.

    Article  CAS  PubMed  Google Scholar 

  69. Giannini C, Hebrink D, Scheithauer BW, Dei Tos AP, James CD. Analysis of p53 mutation and expression in pleomorphic xanthoastrocytoma. Neurogenetics. 2001;3:159–62.

    Article  CAS  PubMed  Google Scholar 

  70. Lassus H, Butzow R. The classification of p53 immunohistochemical staining results and patient outcome in ovarian cancer. Br J Cancer. 2007;96:1621–2; author reply 3–4.

    Google Scholar 

  71. Wade M, Li YC, Wahl GM. MDM2, MDMX and p53 in oncogenesis and cancer therapy. Nat Rev Cancer. 2013;13:83–96.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  72. Biernat W, Kleihues P, Yonekawa Y, Ohgaki H. Amplification and overexpression of MDM2 in primary (de novo) glioblastomas. J Neuropathol Exp Neurol. 1997;56:180–5.

    Article  CAS  PubMed  Google Scholar 

  73. Weaver J, Downs-Kelly E, Goldblum JR, Turner S, Kulkarni S, Tubbs RR, et al. Fluorescence in situ hybridization for MDM2 gene amplification as a diagnostic tool in lipomatous neoplasms. Mod Pathol. 2008;21:943–9.

    Article  CAS  PubMed  Google Scholar 

  74. Zhang W, McElhinny A, Nielsen A, Wang M, Miller M, Singh S, et al. Automated brightfield dual-color in situ hybridization for detection of mouse double minute 2 gene amplification in sarcomas. Appl Immunohistochem Mol Morphol. 2011;19:54–61.

    Article  PubMed  Google Scholar 

  75. Nishio J. Contributions of cytogenetics and molecular cytogenetics to the diagnosis of adipocytic tumors. J Biomed Biotechnol. 2011;2011:524067.

    Article  PubMed  PubMed Central  Google Scholar 

  76. Karlbom AE, James CD, Boethius J, Cavenee WK, Collins VP, Nordenskjold M, et al. Loss of heterozygosity in malignant gliomas involves at least three distinct regions on chromosome 10. Hum Genet. 1993;92:169–74.

    Article  CAS  PubMed  Google Scholar 

  77. Song MS, Salmena L, Pandolfi PP. The functions and regulation of the PTEN tumour suppressor. Nat Rev Mol Cell Biol. 2012;13:283–96.

    CAS  PubMed  Google Scholar 

  78. Duerr EM, Rollbrocker B, Hayashi Y, Peters N, Meyer-Puttlitz B, Louis DN, et al. PTEN mutations in gliomas and glioneuronal tumors. Oncogene. 1998;16:2259–64.

    Article  CAS  PubMed  Google Scholar 

  79. Zhou XP, Marsh DJ, Morrison CD, Chaudhury AR, Maxwell M, Reifenberger G, et al. Germline inactivation of PTEN and dysregulation of the phosphoinositol-3-kinase/Akt pathway cause human Lhermitte-Duclos disease in adults. Am J Hum Genet. 2003;73:1191–8.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  80. Perry A, Miller CR, Gujrati M, Scheithauer BW, Zambrano SC, Jost SC, et al. Malignant gliomas with primitive neuroectodermal tumor-like components: a clinicopathologic and genetic study of 53 cases. Brain Pathol. 2009;19:81–90.

    Article  PubMed  Google Scholar 

  81. Valentino C, Kendrick S, Johnson N, Gascoyne R, Chan WC, Weisenburger D, et al. Colorimetric in situ hybridization identifies MYC gene signal clusters correlating with increased copy number, mRNA, and protein in diffuse large B-cell lymphoma. Am J Clin Pathol. 2013;139:242–54.

    Article  PubMed  PubMed Central  Google Scholar 

  82. Dolecek TA, Propp JM, Stroup NE, Kruchko C. CBTRUS statistical report: primary brain and central nervous system tumors diagnosed in the United States in 2005–2009. Neuro Oncol. 2012;14 Suppl 5:v1–49.

    Article  PubMed  PubMed Central  Google Scholar 

  83. Aldosari N, Bigner SH, Burger PC, Becker L, Kepner JL, Friedman HS, et al. MYCC and MYCN oncogene amplification in medulloblastoma. A fluorescence in situ hybridization study on paraffin sections from the Children’s Oncology Group. Arch Pathol Lab Med. 2002;126:540–4.

    PubMed  Google Scholar 

  84. Pomeroy SL, Tamayo P, Gaasenbeek M, Sturla LM, Angelo M, McLaughlin ME, et al. Prediction of central nervous system embryonal tumour outcome based on gene expression. Nature. 2002;415:436–42.

    Article  CAS  PubMed  Google Scholar 

  85. Eberhart CG, Tihan T, Burger PC. Nuclear localization and mutation of beta-catenin in medulloblastomas. J Neuropathol Exp Neurol. 2000;59:333–7.

    Article  CAS  PubMed  Google Scholar 

  86. Stargatt R, Rosenfeld JV, Anderson V, Hassall T, Maixner W, Ashley D. Intelligence and adaptive function in children diagnosed with brain tumour during infancy. J Neurooncol. 2006;80:295–303.

    Article  PubMed  Google Scholar 

  87. Northcott PA, Korshunov A, Witt H, Hielscher T, Eberhart CG, Mack S, et al. Medulloblastoma comprises four distinct molecular variants. J Clin Oncol. 2011;29:1408–14.

    Article  PubMed  Google Scholar 

  88. Northcott PA, Shih DJ, Peacock J, Garzia L, Morrissy AS, Zichner T, et al. Subgroup-specific structural variation across 1,000 medulloblastoma genomes. Nature. 2012;488:49–56.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  89. Ellison DW, Dalton J, Kocak M, Nicholson SL, Fraga C, Neale G, et al. Medulloblastoma: clinicopathological correlates of SHH, WNT, and non-SHH/WNT molecular subgroups. Acta Neuropathol. 2011;121:381–96.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  90. Greenfield JG, Love S, Louis DN, Ellison D. Greenfield’s neuropathology. 8th ed. London: Hodder Arnold; 2008.

    Google Scholar 

  91. Hasselblatt M, Oyen F, Gesk S, Kordes U, Wrede B, Bergmann M, et al. Cribriform neuroepithelial tumor (CRINET): a nonrhabdoid ventricular tumor with INI1 loss and relatively favorable prognosis. J Neuropathol Exp Neurol. 2009;68:1249–55.

    Article  PubMed  Google Scholar 

  92. Ibrahim GM, Huang A, Halliday W, Dirks PB, Malkin D, Baskin B, et al. Cribriform neuroepithelial tumour: novel clinicopathological, ultrastructural and cytogenetic findings. Acta Neuropathol. 2011;122:511–4.

    Article  PubMed  Google Scholar 

  93. Judkins AR, Burger PC, Hamilton RL, Kleinschmidt-DeMasters B, Perry A, Pomeroy SL, et al. INI1 protein expression distinguishes atypical teratoid/rhabdoid tumor from choroid plexus carcinoma. J Neuropathol Exp Neurol. 2005;64:391–7.

    Article  CAS  PubMed  Google Scholar 

  94. Mobley BC, McKenney JK, Bangs CD, Callahan K, Yeom KW, Schneppenheim R, et al. Loss of SMARCB1/INI1 expression in poorly differentiated chordomas. Acta Neuropathol. 2010;120:745–53.

    Article  CAS  PubMed  Google Scholar 

  95. Hollmann TJ, Hornick JL. INI1-deficient tumors: diagnostic features and molecular genetics. Am J Surg Pathol. 2011;35:e47–63.

    Article  PubMed  Google Scholar 

  96. Hulsebos TJ, Plomp AS, Wolterman RA, Robanus-Maandag EC, Baas F, Wesseling P. Germline mutation of INI1/SMARCB1 in familial schwannomatosis. Am J Hum Genet. 2007;80:805–10.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  97. Patil S, Perry A, Maccollin M, Dong S, Betensky RA, Yeh TH, et al. Immunohistochemical analysis supports a role for INI1/SMARCB1 in hereditary forms of schwannomas, but not in solitary, sporadic schwannomas. Brain Pathol. 2008;18:517–9.

    CAS  PubMed  PubMed Central  Google Scholar 

  98. Chmielecki J, Crago AM, Rosenberg M, O’Connor R, Walker SR, Ambrogio L, et al. Whole-exome sequencing identifies a recurrent NAB2-STAT6 fusion in solitary fibrous tumors. Nat Genet. 2013;45:131–2.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  99. Schweizer L, Koelsche C, Sahm F, Piro RM, Capper D, Reuss DE, et al. Meningeal hemangiopericytoma and solitary fibrous tumors carry the NAB2-STAT6 fusion and can be diagnosed by nuclear expression of STAT6 protein. Acta Neuropathol. 2013;125:651–8.

    Article  CAS  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Jason Karamchandani M.D. .

Editor information

Editors and Affiliations

Rights and permissions

Reprints and permissions

Copyright information

© 2014 Springer Science+Business Media New York

About this chapter

Cite this chapter

Karamchandani, J. (2014). Molecular Testing in CNS tumors. In: Yousef, G., Jothy, S. (eds) Molecular Testing in Cancer. Springer, New York, NY. https://doi.org/10.1007/978-1-4899-8050-2_15

Download citation

  • DOI: https://doi.org/10.1007/978-1-4899-8050-2_15

  • Publisher Name: Springer, New York, NY

  • Print ISBN: 978-1-4899-8049-6

  • Online ISBN: 978-1-4899-8050-2

  • eBook Packages: MedicineMedicine (R0)

Publish with us

Policies and ethics