Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Oncogenomics
  • Published:

Gene expression profiling and subgroup identification of oligodendrogliomas

Oncogene volume 23, pages 6012–6022 (2004)Cite this article

Abstract

The histological diagnosis of low-grade astrocytomas and oligodendrogliomas (WHO grade II) is often challenging, particularly in cases that show both astrocytic and oligodendroglial differentiation. We carried out gene expression profiling on 17 oligodendrogliomas (93% with LOH 1p and/or 19q) and 15 low-grade astrocytomas (71% with a TP53 mutation), using a cDNA array containing 1176 cancer-related genes. In oligodendrogliomas, 40 genes showed on average higher expression (at least a two-fold increase) than in astrocytomas, including DES, TDGF1, TGF-β, GABA-BR1A, Histone H4, CDKN1A, PCDH43, Rho7 and Jun-D, while 39 genes were expressed at lower levels (at least a two-fold decrease), including JNK2, ITGB4, JNK3A2, RhoC, IFI-56K, AAD14 and EGFR. Immunohistochemistry revealed nuclear staining of Jun-D in oligodendrogliomas, in contrast to the immunoreactivity of cytoplasm and cell processes in low-grade astrocytomas. Partial least-squares analysis of the 79 genes at least two-fold differentially expressed between oligodendrogliomas and low-grade astrocytomas demonstrated perfect separation of oligodendrogliomas from low-grade astrocytomas and normal cerebral white matter. Clustering analysis based on the entire gene set divided the 17 subjects with oligodendrogliomas into two subgroups with significantly different survival (log-rank test, P=0.0305; survival to 5-years, 80 vs 0%, P=0.048). These results demonstrate that oligodendrogliomas and low-grade astrocytomas differ in their gene expression profiles, and that there are subgroups of oligodendroglioma with distinct expression profiles related to clinical outcome.

This is a preview of subscription content, access via your institution

Access options

Buy this article

  • Purchase on Springer Link
  • Instant access to full article PDF
Buy now

Prices may be subject to local taxes which are calculated during checkout

Figure 1
Figure 2
Figure 3
Figure 4
Figure 5
Figure 6

Similar content being viewed by others

Accession codes

Accessions

GenBank/EMBL/DDBJ

References

  • Azzarelli BN, Miravalle LN and Vidal RN . (2003). J. Neuropathol. Exp. Neurol., 62, 544.

  • Blumcke I, Becker AJ, Normann S, Hans V, Riederer BM, Krajewski S, Wiestler OD and Reifenberger G . (2001). J. Neuropathol. Exp. Neurol., 60, 984–993.

  • Cairncross JG, Ueki K, Zlatescu MC, Lisle DK, Finkelstein DM, Hammond RR, Silver JS, Stark PC, Macdonald DR, Ino Y, Ramsay DA and Louis DN . (1998). J. Natl. Cancer Inst., 90, 1473–1479.

  • Durand JF, Roman S and Vivien M (eds) (2001). Guide d'utilisation de la Regression Partial Least Squares Lineaire sous Splus. Universite Montpellier II: Montpellier.

    Google Scholar 

  • Fuller GN, Rhee CH, Hess KR, Caskey LS, Wang R, Bruner JM, Yung WK and Zhang W . (1999). Cancer Res., 59, 4228–4232.

  • Grifa A, Totaro A, Rommens JM, Carella M, Roetto A, Borgato L, Zelante L and Gasparini P . (1998). Biochem. Biophys. Res. Commun., 250, 240–245.

  • Gunthert AR, Grundker C, Hollmann K and Emons G . (2002). Biochem. Biophys. Res. Commun., 294, 11–15.

  • Gutmann DH, Hedrick NM, Li J, Nagarajan R, Perry A and Watson MA . (2002). Cancer Res., 62, 2085–2091.

  • Hall A . (1998). Science, 279, 509–514.

  • Huang H, Colella S, Kurrer M, Yonekawa Y, Kleihues P and Ohgaki H . (2000). Cancer Res., 60, 6868–6874.

  • Ino Y, Betensky RA, Zlatescu MC, Sasaki H, Macdonald DR, Stemmer-Rachamimov AO, Ramsay DA, Cairncross JG and Louis DN . (2001). Clin. Cancer Res., 7, 839–845.

  • Kleihues P, Davis RL, Ohgaki H, Burger PC, Westphal MM and Cavenee WK . (2000). Diffuse astrocytoma Pathology and Genetics of Tumours of the Nervous System, Kleihues P and Cavenee WK (eds). IARC Press: Lyon, pp. 22–26.

    Google Scholar 

  • Li T, Dai W and Lu L . (2002). J. Biol. Chem., 277, 32668–32676.

  • Ligon KL, Alberta JA, Louis DN, Stiles CD and Rowitch DH . (2003). J. Neuropathol. Exp. Neurol., 62, 544.

  • Lu QR, Park JK, Noll E, Chan JA, Alberta J, Yuk D, Alzamora MG, Louis DN, Stiles CD, Rowitch DH and Black PM . (2001). Proc. Natl. Acad. Sci. USA, 98, 10851–10856.

  • Marie Y, Sanson M, Mokhtari K, Leuraud P, Kujas M, Delattre JY, Poirier J, Zalc B and Hoang-Xuan K . (2001). Lancet, 358, 298–300.

  • Markert JM, Fuller CM, Gillespie GY, Bubien JK, McLean LA, Hong RL, Lee K, Gullans SR, Mapstone TB and Benos DJ . (2001). Physiol. Genomics, 5, 21–33.

  • Miettinen HE, Paunu N, Rantala I, Kalimo H, Paljarvi L, Helin H and Haapasalo H . (2001). J. Neurooncol., 55, 29–37.

  • Mukasa A, Ueki K, Matsumoto S, Tsutsumi S, Nishikawa R, Fujimaki T, Asai A, Kirino T and Aburatani H . (2002). Oncogene, 21, 3961–3968.

  • Nguyen DV and Rocke DM . (2002). Bioinformatics, 18, 39–50.

  • Nigro JM, Takahashi MA, Ginzinger DG, Law M, Passe S, Jenkins RB and Aldape K . (2001). Am. J. Pathol., 158, 1253–1262.

  • Nutt CL, Mani DR, Betensky RA, Tamayo P, Cairncross JG, Ladd C, Pohl U, Hartmann C, McLaughlin ME, Batchelor TT, Black PM, von Deimling A, Pomeroy SL, Golub TR and Louis DN . (2003). Cancer Res., 63, 1602–1607.

  • Obata S, Sago H, Mori N, Rochelle JM, Seldin MF, Davidson M, St John T, Taketani S and Suzuki ST . (1995). J. Cell. Sci., 108 (Part 12), 3765–3773.

  • Ohnishi A, Sawa H, Tsuda M, Sawamura Y, Itoh T, Iwasaki Y and Nagashima K . (2003). J. Neuropathol. Exp. Neurol., 62, 1052–1059.

  • Perry JR . (2001). Curr. Opin. Neurol., 14, 705–710.

  • Peters HC, Kammer G, Volz A, Kaupmann K, Ziegler A, Bettler B, Epplen JT, Sander T and Riess O . (1998). Neurogenetics, 2, 47–54.

  • Reifenberger G, Kros JM, Burger PC, Louis DN and Collins VP . (2000). Oligodendroglioma Pathology and Genetics of Tumours of the Nervous System, Kleihues P and Cavenee WK (eds). IARC Press: Lyon, pp. 56–61.

    Google Scholar 

  • Reifenberger J, Reifenberger G, Liu L, James CD, Wechsler W and Collins VP . (1994). Am. J. Pathol., 145, 1175–1190.

  • Rickman DS, Bobek MP, Misek DE, Kuick R, Blaivas M, Kurnit DM, Taylor J and Hanash SM . (2001). Cancer Res., 61, 6885–6891.

  • Sallinen SL, Sallinen PK, Haapasalo HK, Helin HJ, Helen PT, Schraml P, Kallioniemi OP and Kononen J . (2000). Cancer Res., 60, 6617–6622.

  • Sano K, Tanihara H, Heimark RL, Obata S, Davidson M, St John T, Taketani S and Suzuki S . (1993). EMBO J., 12, 2249–2256.

  • Schafer JL (ed) (1997). Analysis of Incomplete Multivariate Date. Chapman & Hall: London.

    Book  Google Scholar 

  • Smith JS, Perry A, Borell TJ, Lee HK, O'Fallon J, Hosek SM, Kimmel D, Yates A, Burger PC, Scheithauer BW and Jenkins RB . (2000). J. Clin. Oncol., 18, 636–645.

  • Tanwar MK, Gilbert MR and Holland EC . (2002). Cancer Res., 62, 4364–4368.

  • Vogt PK . (2001). Oncogene, 20, 2365–2377.

  • Wagner EF . (2001). Oncogene, 20, 2334–2335.

  • Watanabe K, Tachibana O, Sato K, Yonekawa Y, Kleihues P and Ohgaki H . (1996). Brain Pathol., 6, 217–224.

  • Watanabe T, Nakamura M, Kros JM, Burkhard C, Yonekawa Y, Kleihues P and Ohgaki H . (2001). Acta Neuropathol., 103, 267–275.

  • Watson MA, Perry A, Budhjara V, Hicks C, Shannon WD and Rich KM . (2001). Cancer Res., 61, 1825–1829.

  • Zerbini LF, Wang Y, Cho JY and Libermann TA . (2003). Cancer Res., 63, 2206–2215.

Download references

Acknowledgements

This study was supported by a grant of the Foundation for Promotion of Cancer Research, Japan. FLH is a fellow of the Leopoldina foundation and supported by grants of the Bonizzi-Theler- and Stammbach foundation. We are grateful to Mrs N Lyandrat for the technical assistance.

Author information

Authors and Affiliations

  1. International Agency for Research on Cancer (IARC), 150 Cours Albert-Thomas, Lyon, Cedex 08, F-69372, France

    Hervé Huang, Yoshikazu Okamoto, Hideaki Yokoo, Emmanuel N Lazaridis, Paul Kleihues & Hiroko Ohgaki

  2. Institute of Neuropathology, University Hospital Zurich, Zurich, CH-8091, Switzerland

    Frank L Heppner

  3. Department of Neuropathology, Victor Segalen University, Bordeaux, F-33076, France

    Anne Vital

  4. Department of Neuropathology, Neurological and Neurosurgical Hospital, Lyon, F-69394, France

    Michelle Fevre-Montange & Anne Jouvet

  5. Department of Neurosurgery, University Hospital Zurich, Zurich, CH-8091, Switzerland

    Yasuhiro Yonekawa

Authors
  1. Hervé Huang
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Yoshikazu Okamoto
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Hideaki Yokoo
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Frank L Heppner
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Anne Vital
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Michelle Fevre-Montange
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Anne Jouvet
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Yasuhiro Yonekawa
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Emmanuel N Lazaridis
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. Paul Kleihues
    View author publications

    You can also search for this author in PubMed Google Scholar

  11. Hiroko Ohgaki
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Hiroko Ohgaki.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Huang, H., Okamoto, Y., Yokoo, H. et al. Gene expression profiling and subgroup identification of oligodendrogliomas. Oncogene 23, 6012–6022 (2004). https://doi.org/10.1038/sj.onc.1207781

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/sj.onc.1207781

Keywords

This article is cited by

Search

Advanced search

Quick links