Skip to main content
SpringerLink
Log in

Detection of genetic and chromosomal aberrations in medulloblastomas and primitive neuroectodermal tumors with DNA microarrays

  • ORIGINAL ARTICLE
  • Published:
Brain Tumor Pathology Aims and scope Submit manuscript

Abstract

Medulloblastoma (MB) is the most frequent infratentorial malignant brain tumor in children. In contrast, primitive neuroectodermal tumor (PNET) is defined as a supratentorial malignant tumor generated from the cerebral hemisphere. These tumors have considerable histological overlap but have different clinical outcomes including overall survival period, recurrence rate, and chemosensitivity. We investigated the amplification and/or deletion of genes and the chromosomal gain and/or loss in 10 MBs and 3 PNETs with a genomic DNA microarray system. Genes that are frequently amplified in these both these tumors include MSH2, N-myc, AKT3, and EGFR. Amplifications of SNRPN, MYB, and PTEN are observed only in MB. The genes associated with Wnt/APC and Shh/PTCH pathways also have some aberrations. Common chromosomal aberrations include gains at 17q and 7q and losses at 17p. Minor chromosomal losses were also detected at 1p, 8p + q, 11p, 10p + q, 13q, 16q, and Xp + q in MB. SPNETs tend to contain fewer chromosomal and genetic abnormalities than MBs. In conclusion, there are gene expression and chromosomal differences between MBs and SPNETs. These differences may correlate with the prognosis.

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

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  1. P Kleihues DN Louis BW Scheithauer et al. (2002) ArticleTitleThe WHO classification of tumors of the nervous system J Neuropathol Exp Neurol 61 215–225 Occurrence Handle11895036

    PubMed  Google Scholar 

  2. PR Thomas M Deutsch JL Kepner et al. (2000) ArticleTitleLow-stage medulloblastoma: final analysis of trial comparing standard-dose with reduced-dose neuraxis irradiation J Clin Oncol 18 3004–3011 Occurrence Handle10944134 Occurrence Handle1:STN:280:DC%2BD3cvivFCktw%3D%3D

    PubMed  CAS  Google Scholar 

  3. RJ Packer J Goldwein HS Nicholson et al. (1999) ArticleTitleTreatment of children with medulloblastomas with reduced-dose craniospinal radiation therapy and adjuvant chemotherapy: a Children's Cancer Group Study J Clin Oncol 17 2127–2136 Occurrence Handle10561268 Occurrence Handle1:CAS:528:DyaK1MXkvVSmur8%3D

    PubMed  CAS  Google Scholar 

  4. SL Pomeroy P Tamayo M Gaasenbeek et al. (2002) ArticleTitlePrediction of central nervous system embryonal tumour outcome based on gene expression Nature (Lond) 415 436–442 Occurrence Handle1:CAS:528:DC%2BD38XhtVCqtr0%3D Occurrence Handle10.1038/415436a

    Article  CAS  Google Scholar 

  5. C Russo M Pellarin O Tingby et al. (1999) ArticleTitleComparative genomic hybridization in patients with supratentorial and infratentorial primitive neuroectodermal tumors Cancer (Phila) 86 331–339 Occurrence Handle1:STN:280:DyaK1MzkslKgug%3D%3D Occurrence Handle10.1002/(SICI)1097-0142(19990715)86:2<331::AID-CNCR18>3.0.CO;2-#

    Article  CAS  Google Scholar 

  6. M Maruno T Yoshimine AK Muhammad et al. (1998) ArticleTitleChromosomal losses and gains in meningiomas: comparative genomic hybridization (CGH) study of the whole genome Neurol Res 20 612–616 Occurrence Handle9785589 Occurrence Handle1:STN:280:DyaK1M%2FgtFOlug%3D%3D

    PubMed  CAS  Google Scholar 

  7. M Maruno H Ninomiya AK Ghulam Muhammad et al. (2000) ArticleTitleWhole-genome analysis of human astrocytic tumors by comparative genomic hybridization Brain Tumor Pathol 17 21–27 Occurrence Handle10982006 Occurrence Handle1:CAS:528:DC%2BD3cXntFOmsL8%3D

    PubMed  CAS  Google Scholar 

  8. T Suzuki M Maruno K Wada et al. (2004) ArticleTitleGenetic analysis of human glioblastomas using a genomic microarray system Brain Tumor Pathol 21 27–34 Occurrence Handle15696966 Occurrence Handle1:CAS:528:DC%2BD2MXht12hu73L

    PubMed  CAS  Google Scholar 

  9. K Wada M Maruno T Suzuki et al. (2005) ArticleTitleChromosomal and genetic abnormalities in benign and malignant meningiomas using DNA microarray Neurol Res 27 747–754 Occurrence Handle16197812 Occurrence Handle1:CAS:528:DC%2BD2MXht1Wkt7fM Occurrence Handle10.1179/016164105X35648

    Article  PubMed  CAS  Google Scholar 

  10. J Nicholson C Wickramasinghe F Ross et al. (2000) ArticleTitleImbalances of chromosome 17 in medulloblastomas determined by comparative genomic hybridisation and fluorescence in situ hybridisation Mol Pathol 53 313–319 Occurrence Handle11193050 Occurrence Handle1:CAS:528:DC%2BD3MXhtlOnug%3D%3D Occurrence Handle10.1136/mp.53.6.313

    Article  PubMed  CAS  Google Scholar 

  11. DA Reardon E Michalkiewicz JM Boyett et al. (1997) ArticleTitleExtensive genomic abnormalities in childhood medulloblastoma by comparative genomic hybridization Cancer Res 57 4042–4047 Occurrence Handle9307291 Occurrence Handle1:CAS:528:DyaK2sXmtFehsbw%3D

    PubMed  CAS  Google Scholar 

  12. N Aldosari SH Bigner PC Burger et al. (2002) ArticleTitleMYCC 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 126 540–544 Occurrence Handle11958658

    PubMed  Google Scholar 

  13. WG Scheurlen P Seranski A Mincheva et al. (1997) ArticleTitleHigh-resolution deletion mapping of chromosome arm 17p in childhood primitive neuroectodermal tumors reveals a common chromosomal disruption within the Smith–Magenis region, an unstable region in chromosome band 17p11.2 Genes Chromosomes Cancer 18 50–58 Occurrence Handle8993980 Occurrence Handle1:CAS:528:DyaK2sXnvFKmsg%3D%3D Occurrence Handle10.1002/(SICI)1098-2264(199701)18:1<50::AID-GCC6>3.0.CO;2-0

    Article  PubMed  CAS  Google Scholar 

  14. MM Inda C Perot M Guillaud-Bataille et al. (2005) ArticleTitleGenetic heterogeneity in supratentorial and infratentorial primitive neuroectodermal tumours of the central nervous system Histopathology (Oxf) 47 631–637 Occurrence Handle1:STN:280:DC%2BD2MnksV2htQ%3D%3D Occurrence Handle10.1111/j.1365-2559.2005.02304.x

    Article  CAS  Google Scholar 

  15. ME Burnett EC White S Sih et al. (1997) ArticleTitleChromosome arm 17p deletion analysis reveals molecular genetic heterogeneity in supratentorial and infratentorial primitive neuroectodermal tumors of the central nervous system Cancer Genet Cytogenet 97 25–31 Occurrence Handle9242214 Occurrence Handle1:CAS:528:DyaK2sXlsVGitrY%3D Occurrence Handle10.1016/S0165-4608(96)00319-6

    Article  PubMed  CAS  Google Scholar 

  16. WG Scheurlen GC Schwabe S Joos et al. (1998) ArticleTitleMolecular analysis of childhood primitive neuroectodermal tumors defines markers associated with poor outcome J Clin Oncol 16 2478–2485 Occurrence Handle9667267 Occurrence Handle1:STN:280:DyaK1czivFynsw%3D%3D

    PubMed  CAS  Google Scholar 

  17. D Ellison (2002) ArticleTitleClassifying the medulloblastoma: insights from morphology and molecular genetics Neuropathol Appl Neurobiol 28 257–282 Occurrence Handle12175339 Occurrence Handle1:CAS:528:DC%2BD38XnsVSntbo%3D Occurrence Handle10.1046/j.1365-2990.2002.00419.x

    Article  PubMed  CAS  Google Scholar 

  18. BR Schutz W Scheurlen J Krauss et al. (1996) ArticleTitleMapping of chromosomal gains and losses in primitive neuroectodermal tumors by comparative genomic hybridization Genes Chromosomes Cancer 16 196–203 Occurrence Handle8814453 Occurrence Handle1:STN:280:DyaK28vgvFCksw%3D%3D Occurrence Handle10.1002/(SICI)1098-2264(199607)16:3<196::AID-GCC7>3.0.CO;2-U

    Article  PubMed  CAS  Google Scholar 

  19. HJ Gilhuis KL Anderl RH Boerman et al. (2000) ArticleTitleComparative genomic hybridization of medulloblastomas and clinical relevance: eleven new cases and a review of the literature Clin Neurol Neurosurg 102 203–209 Occurrence Handle11154805 Occurrence Handle1:STN:280:DC%2BD3M7ktVKhsQ%3D%3D Occurrence Handle10.1016/S0303-8467(00)00112-8

    Article  PubMed  CAS  Google Scholar 

  20. CA Griffin AL Hawkins RJ Packer et al. (1988) ArticleTitleChromosome abnormalities in pediatric brain tumors Cancer Res 48 175–180 Occurrence Handle3334992 Occurrence Handle1:STN:280:DyaL1c%2FotVSjsw%3D%3D

    PubMed  CAS  Google Scholar 

  21. CG Eberhart J Kratz Y Wang et al. (2004) ArticleTitleHistopathological and molecular prognostic markers in medulloblastoma: c-myc, N-myc, TrkC, and anaplasia J Neuropathol Exp Neurol 63 441–449 Occurrence Handle15198123 Occurrence Handle1:CAS:528:DC%2BD2cXlt1emu7o%3D

    PubMed  CAS  Google Scholar 

  22. CG Eberhart JE Kratz A Schuster et al. (2002) ArticleTitleComparative genomic hybridization detects an increased number of chromosomal alterations in large cell/anaplastic medulloblastomas Brain Pathol 12 36–44 Occurrence Handle11770900 Occurrence Handle1:CAS:528:DC%2BD38XlvVSmt78%3D Occurrence Handle10.1111/j.1750-3639.2002.tb00420.x

    Article  PubMed  CAS  Google Scholar 

  23. JR Leonard DX Cai DJ Rivet et al. (2001) ArticleTitleLarge cell/anaplastic medulloblastomas and medullomyoblastomas: clinicopathological and genetic features J Neurosurg 95 82–88 Occurrence Handle11453402 Occurrence Handle1:STN:280:DC%2BD3Mvgt1CrtA%3D%3D Occurrence Handle10.3171/jns.2001.95.1.0082

    Article  PubMed  CAS  Google Scholar 

  24. J Herms I Neidt B Luscher et al. (2000) ArticleTitleC-MYC expression in medulloblastoma and its prognostic value Int J Cancer 89 395–402 Occurrence Handle11008200 Occurrence Handle1:CAS:528:DC%2BD3cXnsFWmsro%3D Occurrence Handle10.1002/1097-0215(20000920)89:5<395::AID-IJC1>3.0.CO;2-V

    Article  PubMed  CAS  Google Scholar 

  25. TG Oliver LL Grasfeder AL Carroll et al. (2003) ArticleTitleTranscriptional profiling of the Sonic hedgehog response: a critical role for N-myc in proliferation of neuronal precursors Proc Natl Acad Sci U S A 100 7331–7336 Occurrence Handle12777630 Occurrence Handle1:CAS:528:DC%2BD3sXkslOmsLo%3D Occurrence Handle10.1073/pnas.0832317100

    Article  PubMed  CAS  Google Scholar 

  26. K Hashimoto C Azuma Y Tokugawa et al. (1997) ArticleTitleLoss of H19 imprinting and up-regulation of H19 and SNRPN in a case with malignant mixed Mullerian tumor of the uterus Hum Pathol 28 862–865 Occurrence Handle9224757 Occurrence Handle1:STN:280:DyaK2szmsl2qsg%3D%3D Occurrence Handle10.1016/S0046-8177(97)90162-3

    Article  PubMed  CAS  Google Scholar 

  27. MM Inda J Mercapide J Munoz et al. (2004) ArticleTitlePTEN and DMBT1 homozygous deletion and expression in medulloblastomas and supratentorial primitive neuroectodermal tumors Oncol Rep 12 1341–1347 Occurrence Handle15547761

    PubMed  Google Scholar 

  28. M Zakrzewska P Rieske M Debiec-Rychter et al. (2004) ArticleTitleMolecular abnormalities in pediatric embryonal brain tumors – analysis of loss of heterozygosity on chromosomes 1, 5, 9, 10, 11, 16, 17 and 22 Clin Neuropathol 23 209–217 Occurrence Handle15581023 Occurrence Handle1:STN:280:DC%2BD2cngslClsQ%3D%3D

    PubMed  CAS  Google Scholar 

  29. JC Pang Z Dong R Zhang et al. (2003) ArticleTitleMutation analysis of DMBT1 in glioblastoma, medulloblastoma and oligodendroglial tumors Int J Cancer 105 76–81 Occurrence Handle12672033 Occurrence Handle1:CAS:528:DC%2BD3sXjtVWrsrY%3D Occurrence Handle10.1002/ijc.11019

    Article  PubMed  CAS  Google Scholar 

  30. G Marra I Iaccarino T Lettieri et al. (1998) ArticleTitleMismatch repair deficiency associated with overexpression of the MSH3 gene Proc Natl Acad Sci U S A 95 8568–8573 Occurrence Handle9671718 Occurrence Handle1:CAS:528:DyaK1cXkvFamu7c%3D Occurrence Handle10.1073/pnas.95.15.8568

    Article  PubMed  CAS  Google Scholar 

  31. SE Andrew M McKinnon BS Cheng et al. (1998) ArticleTitleTissues of MSH2-deficient mice demonstrate hypermutability on exposure to a DNA methylating agent Proc Natl Acad Sci U S A 95 1126–1130 Occurrence Handle9448296 Occurrence Handle1:CAS:528:DyaK1cXosFSkug%3D%3D Occurrence Handle10.1073/pnas.95.3.1126

    Article  PubMed  CAS  Google Scholar 

  32. A Koch A Waha JC Tonn et al. (2001) ArticleTitleSomatic mutations of WNT/wingless signaling pathway components in primitive neuroectodermal tumors Int J Cancer 93 445–449 Occurrence Handle11433413 Occurrence Handle1:CAS:528:DC%2BD3MXlt12gtr4%3D Occurrence Handle10.1002/ijc.1342

    Article  PubMed  CAS  Google Scholar 

  33. H Huang BM Mahler-Araujo A Sankila et al. (2000) ArticleTitleAPC mutations in sporadic medulloblastomas Am J Pathol 156 433–437 Occurrence Handle10666372 Occurrence Handle1:CAS:528:DC%2BD3cXhtlGgurs%3D

    PubMed  CAS  Google Scholar 

  34. RH Zurawel C Allen S Chiappa et al. (2000) ArticleTitleAnalysis of PTCH/SMO/SHH pathway genes in medulloblastoma Genes Chromosomes Cancer 27 44–51 Occurrence Handle10564585 Occurrence Handle1:CAS:528:DC%2BD3cXksFyr Occurrence Handle10.1002/(SICI)1098-2264(200001)27:1<44::AID-GCC6>3.0.CO;2-V

    Article  PubMed  CAS  Google Scholar 

  35. RJ Wechsler-Reya MP Scott (1999) ArticleTitleControl of neuronal precursor proliferation in the cerebellum by Sonic Hedgehog Neuron 22 103–114 Occurrence Handle10027293 Occurrence Handle1:CAS:528:DyaK1MXhtVGiu7k%3D Occurrence Handle10.1016/S0896-6273(00)80682-0

    Article  PubMed  CAS  Google Scholar 

  36. AO Vortmeyer T Stavrou D Selby et al. (1999) ArticleTitleDeletion analysis of the adenomatous polyposis coli and PTCH gene loci in patients with sporadic and nevoid basal cell carcinoma syndrome-associated medulloblastoma Cancer (Phila) 85 2662–2667 Occurrence Handle1:STN:280:DyaK1MzgtFKmsA%3D%3D Occurrence Handle10.1002/(SICI)1097-0142(19990615)85:12<2662::AID-CNCR24>3.0.CO;2-0

    Article  CAS  Google Scholar 

  37. RH Zurawel SA Chiappa C Allen et al. (1998) ArticleTitleSporadic medulloblastomas contain oncogenic beta-catenin mutations Cancer Res 58 896–899 Occurrence Handle9500446 Occurrence Handle1:CAS:528:DyaK1cXhsFersr8%3D

    PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Neurosurgery, Osaka University Graduate School of Medicine, 2-2 Yamadaka, Suita, Osaka, 565-0871, Japan

    Naoki Kagawa, Motohiko Maruno, Tsuyoshi Suzuki, Tetsuo Hashiba, Naoya Hashimoto, Shuichi Izumoto & Toshiki Yoshimine

Authors
  1. Naoki Kagawa
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Motohiko Maruno
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Tsuyoshi Suzuki
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Tetsuo Hashiba
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Naoya Hashimoto
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Shuichi Izumoto
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Toshiki Yoshimine
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Motohiko Maruno.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Kagawa, N., Maruno, M., Suzuki, T. et al. Detection of genetic and chromosomal aberrations in medulloblastomas and primitive neuroectodermal tumors with DNA microarrays. Brain Tumor Pathol 23, 41–47 (2006). https://doi.org/10.1007/s10014-006-0201-1

Download citation

  • Received:

  • Accepted:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10014-006-0201-1

Key words

Search

Navigation