Medulloblastoma: Role of MYCN Gene Amplification Using Fluorescence In Situ Hybridization and Real Time Quantitative PCR Methods

  • Cecilia SuraceEmail author
Part of the Pediatric Cancer book series (PECA, volume 3)


Gene amplification is a mechanism that can activate cellular oncogenes to express abnormal levels of protein. The MYCN (v-myc myelocytomatosis viral-related oncogene) gene was the first amplified oncogene that was demonstrated to have a clinical significance in neuroblastoma. Moreover, it has also been reported in medulloblastoma, a malignant and invasive embryonal tumor of the central nervous system. In recent years, the improvement of cytomolecular techniques, such as fluorescence in situ hybridization (FISH) and real time quantitative polymerase chain reaction (RQ-PCR), has supplemented the classical cytogenetic analysis for diagnosis and prognosis of medulloblastoma. FISH has advanced the detection of gene amplification revealing episomes, not visible at the karyotype level and it has represented a powerful tool for investigating gene amplification on archival material. RQ-PCR analysis has been used for detecting MYCN copy number alterations and refining the breakpoints of the amplicon containing MYCN at higher resolution. Thus, these techniques investigating the MYCN amplification, have helped to identify a trend towards poorer outcomes in patients and, in combination with histo-pathological assessment, in the next future hopefully will assist a refined classifi­cation of medulloblastoma.


Real Time Quantitative Polymerase Chain Reaction Copy Number Change MYCN Amplification MYCN Gene Real Time Quantitative Polymerase Chain Reaction Analysis 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


  1. Aldosari N, Bigner SH, Burger PC, Becker L, Kepner JL, Friedman HS, McLendon RE (2002) MYCC and MYCN oncogene amplification in medulloblastoma. Arch Pathol Lab Med 126:540–544PubMedGoogle Scholar
  2. Bailey P, Cushing H (1925) Medulloblastoma cerebelli. Arch Neurol Psychiatry 14:192–223CrossRefGoogle Scholar
  3. Bayani J, Zielenska M, Marrano P, Ng YK, Taylor MD, Jay V, Rutka JT, Squire JA (2000) Molecular cytogenetic analysis of medulloblastomas and supratentorial primitive neuroectodermal tumors by using conventional banding, comparative genomic hybridization, and spectral karyotyping. J Neurosurg 93:437–448PubMedCrossRefGoogle Scholar
  4. Bigner SH, Mark J, Friedman HS, Biegel JA, Bigner DD (1988) Structural chromosomal abnormalities in human medulloblastoma. Cancer Genet Cytogenet 30:91–101PubMedCrossRefGoogle Scholar
  5. Brown HG, Kepner JL, Perlman EJ, Friedman HS, Strother DR, Duffner PK, Kun LE, Goldthwaite PT, Burger PC (2000) Large cell/anaplastic medulloblastomas: a Pediatric Oncology Group Study. J Neuropathol Exp Neurol 59:857–865PubMedGoogle Scholar
  6. Capodano AM (2000) Nervous system tumors: medulloblastoma. Atlas Genet Cytogenet Oncol Hematol.
  7. Corvi R, Amler LC, Savelyeva L, Gehring M, Schwab M (1994) MYCN is retained in single copy at chromosome 2 band p23–24 during amplification in human neuroblastoma cells. Proc Natl Acad Sci U S A 91:5523–5527PubMedCentralPubMedCrossRefGoogle Scholar
  8. Crnogorac-Jurcevic T, Efthimiou E, Capelli P, Blaveri E, Baron A, Terris B, Jones M, Tyson K, Bassi C, Scarpa A, Lemoine NR (2001) Gene expression profiles of pancreatic cancer and stromal desmoplasia. Oncogene 20:7437–7446PubMedCrossRefGoogle Scholar
  9. Eberhart CG, Kratz JE, Schuster A, Goldthwaite P, Cohen KJ, Perlman EJ, Burger PC (2002) Comparative genomic hybridization detects an increased number of chromosomal alterations in large cell/anaplastic medulloblastomas. Brain Pathol 12:36–44PubMedCrossRefGoogle Scholar
  10. Eberhart CG, Kratz JE, Wang Y, Summers K, Stearns D, Cohen K, Dang CV, Burger PC (2004) Histopathological and molecular prognostic markers in medulloblastoma: c-myc, N-myc, TrkC, and anaplasia. J Neuropathol Exp Neurol 63:441–449PubMedGoogle Scholar
  11. Ellison D (2002) Classifying the medulloblastoma: insights from morphology and molecular genetics. Neuropathol Appl Neurobiol 28:257–282PubMedCrossRefGoogle Scholar
  12. Frühwald MC, O’Dorisio MS, Rush LJ, Reiter JL, Smiraglia DJ, Wenger G, Costello JF, White PS, Krahe R, Brodeur GM, Plass C (2000) Gene amplification in PNETs/medulloblastomas: mapping of a novel amplified gene within the MYCN amplicon. J Med Genet 37:501–509PubMedCrossRefGoogle Scholar
  13. Giangaspero F, Wellek S, Masuoka J, Gessi M, Kleihues P, Ohgaki H (2006) Stratification of medulloblastoma on the basis of histopathological grading. Acta Neuropathol 112:5–12PubMedCrossRefGoogle Scholar
  14. Graux C, Cools J, Melotte C, Quentmeier H, Ferrando A, Levine R, Vermeesch JR, Stul M, Dutta B, Boeckx N, Bosly A, Heimann P, Uyttebroeck A, Mentens N, Somers R, MavLeod RAF, Drexler HG, Look AT, Gilliland DG, Michaux L, Vandenberghe P, Wlodarska I, Marynen P, Hagemejijer A (2004) Fusion of NUP214 to ABL on amplified episomes in T-cell acute lymphoblastic leukemia. Nat Genet 36:1084–1089PubMedCrossRefGoogle Scholar
  15. Kim SY, Lee MJ, Cho KC, Choi YS, Choi JS, Sung KW, Kwon OJ, Kim HS, Kim IK, Jeong SW (2003) Alterations in mRNA expression of ribosomal protein S9 in hydrogen peroxide-treated neurotumor cells and in rat hippocampus after transient ischemia. Neurochem Res 28:925–931PubMedCrossRefGoogle Scholar
  16. Knoepfler PS, Cheng PF, Eisenman RN (2002) N-MYC is essential during neurogenesis for the rapid expansion of progenitor cell populations and inhibition of neuronal differentiation. Genes Dev 16:2699–2712PubMedCrossRefGoogle Scholar
  17. Korshunov A, Benner A, Remke M, Lichter P, von Deimling A, Pfister S (2008) Accumulation of genomic aberrations during clinical progression of medulloblastoma. Acta Neuropathol 116:383–390PubMedCrossRefGoogle Scholar
  18. Lamont JM, McManamy CS, Pearson AD, Clifford SC, Ellison DW (2004) Combined histopathological and molecular cytogenetic stratification of medulloblastoma patients. Clin Cancer Res 10:5482–5493PubMedCrossRefGoogle Scholar
  19. Lo KC, Rossi MR, Eberhart CG, Cowell JK (2007) Genome wide copy number abnormalities in pediatric medulloblastomas as assessed by array comparative genome hybridization. Brain Pathol 17:282–296PubMedCrossRefGoogle Scholar
  20. Louis DN, Ohgaki H, Wiestler OD, Cavenee WK, Burger PC, Jouvet A, Scheithauer BW, Kleihues P (2007) The 2007 WHO classification of tumours of the central nervous system. Acta Neuropathol 114:97–109PubMedCentralPubMedCrossRefGoogle Scholar
  21. Malakho SG, Korshunov A, Stroganova AM, Poltaraus AB (2008) Fast detection of MYCN copy number alterations in brain neuronal tumors by real-time PCR. J Clin Lab Anal 22:123–130PubMedCrossRefGoogle Scholar
  22. Min HS, Lee YJ, Park K, Cho BK, Park SH (2006) Medulloblastoma: histopathologic and molecular markers of anaplasia and biologic behavior. Acta Neuropathol 112:13–20PubMedCrossRefGoogle Scholar
  23. Polkinghorn W, Tarbell N (2007) Medulloblastoma: tumorigenesis, current clinical paradigm, and efforts to improve risk stratification. Nat Clin Pract Oncol 4:295–304PubMedCrossRefGoogle Scholar
  24. Raggi CC, Bagnoni ML, Tonini GP, Maggi M, Vona G, Pinzani P, Mazzocco K, De Bernardi B, Pazzagli M, Orlando C (1999) Real-time quantitative PCR for the measurement of MYCN amplification in human neuroblastoma with the TaqMan detection system. Clin Chem 45:1918–1924PubMedGoogle Scholar
  25. Rossi MR, Conroy J, McQuaid D, Nowak NJ, Rutka JT, Cowell JK (2006) Array CGH analysis of pediatric medulloblastomas. Genes Chromosomes Cancer 45:290–303PubMedCrossRefGoogle Scholar
  26. Savelyeva L, Schwab M (2001) Amplification of oncogenes revisited: from expression profiling to clinical application. Cancer Lett 167:115–123PubMedCrossRefGoogle Scholar
  27. Schwab M, Amler L (1990) Amplification of cellular oncogenes: a predictor of clinical outcome in human cancer. Genes Chromosomes Cancer 1:181–193PubMedCrossRefGoogle Scholar
  28. Surace C, Pedeutour F, Trombetta D, Burel-Vandenbos F, Rocchi M, Storlazzi CT (2008) Episomal amplification of MYCN in a case of medulloblastoma. Virchows Arch 425:491–497CrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media Dordrecht 2012

Authors and Affiliations

  1. 1.Cytogenetics and Molecular GeneticsChildren’s Hospital “Bambino Gesú”RomeItaly

Personalised recommendations