Skip to main content

Advertisement

SpringerLink
Log in

Whole-genomic survey of oligodendroglial tumors: correlation between allelic imbalances and gene expression profiles

  • Laboratory Investigation - Human/Animal Tissue
  • Published:
Journal of Neuro-Oncology Aims and scope Submit manuscript

Abstract

Malignant gliomas are the most common subtype of primary central nervous system (CNS) tumors. Their pathological classification, however, remains subjective, stimulating researchers to actively seek objective molecular markers to discover alternative and more reproducible tools for improved subtypification. Herein, we present a global survey of genomic alterations in oligodendroglial tumors (OT). Genetic and epigenetic alterations identified in this study are correlated with OT molecular groups we have recently reported: a neurogenic group composed of tumors with loss of heterozygosity (LOH) at 1p-19q, IDH1 mutations, and MGMT promoter methylation, showing good prognosis; an intermediate group, presenting TP53 mutations or LOH at 17p, IDH1 mutations, and GSTP1 promoter methylation; and a proliferative group, presenting major genetic alterations (LOH at 10q, EGFR amplification, and CDKN2A/ARF deletion) and poor prognosis. These results allowed us to refine our molecular characterization associated with prognosis, referring exclusively to oligodendroglial tumors.

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

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5

Similar content being viewed by others

References

  1. Louis DN, Ohgaki H, Wiestler OD, Cavenee WK, Burger PC, Jouvet A, Scheithauer BW, Kleihues P (2007) The 2007 WHO classification of tumors of the central nervous system. Acta Neuropathol 114:97–109

    Article  PubMed  Google Scholar 

  2. 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, Louis DN (2003) Gene expression-based classification of malignant gliomas correlates better with survival than histological classification. Cancer Res 63:1602–1607

    PubMed  CAS  Google Scholar 

  3. French PJ, Swagemakers SMA, Nagel JHA, Kouwenhoven MCM, Brouwer E, van der Spek P, Luider TM, Kros JM, van den Bent MJ, Smitt PAS (2005) Gene expression profiles associated with treatment response in Oligodendrogliomas. Cancer Res 65:11335–11344

    Article  PubMed  CAS  Google Scholar 

  4. Ferrer-Luna R, Mata M, Nunez L, Calvar J, Dasi F, Arias E, Piquer J, Cerda-Nicolas M, Taratuto AL, Sevlever G, Celda B, Martinetto H (2009) Loss of heterozygosity at 1p-19q induces a global change in oligodendroglial tumor gene expression. J Neurooncol 95:343–354

    Article  PubMed  CAS  Google Scholar 

  5. Griffin CA, Burger P, Morsberger L, Yonescu R, Swierczynski S, Weingart JD, Murphy KM (2006) Identification of der(1;19)(q10;p10) in five oligodendrogliomas suggests mechanism of concurrent 1p and 19q loss. J Neuropathol Exp Neurol 65:988–994

    Article  PubMed  Google Scholar 

  6. Bigner SH, Matthews MR, Rasheed BK, Wiltshire RN, Friedman HS, Friedman AH, Stenzel TT, Dawes DM, McLendon RE, Bigner DD (1999) Molecular genetic aspects of oligodendrogliomas including analysis by comparative genomic hybridization. Am J Pathol 155:375–386

    Article  PubMed  CAS  Google Scholar 

  7. Jeuken JWM, Sprenger SHE, Wesseling P, Macville MVE, von Deimling A, Teepen H, van Overbeeke JJ, Boerman RH (1999) Identification of subgroups of high-grade oligodendroglial tumors by comparative genomic hybridization. J Neuropathol Exp Neurol 58:606–612

    Article  PubMed  CAS  Google Scholar 

  8. Reifenberger J, Reifenberger G, Liu L, James CD, Wechsler W, Collins VP (1994) Molecular genetic analysis of oligodendroglial tumors shows preferential allelic deletions on 19q and 1p. Am J Pathol 145:1175–1190

    PubMed  CAS  Google Scholar 

  9. Smith JS, Perry A, Borell TJ, Lee HK, O’Fallon J, Hosek SM, Kimmel D, Yates A, Burger PC, Scheithauer BW, Jenkins RB (2000) Alterations of chromosome arms 1p and 19q as predictors of survival in oligodendrogliomas, astrocytomas, and mixed oligoastrocytomas. J Clin Oncol 18:636–645

    PubMed  CAS  Google Scholar 

  10. Watanabe T, Nakamura M, Kros JM, Burkhard C, Yonekawa Y, Kleihues P, Ohgaki H (2002) Phenotype versus genotype correlation in oligodendrogliomas and low-grade diffuse astrocytomas. Acta Neuropathol 103:267–275

    Article  PubMed  CAS  Google Scholar 

  11. Jeuken JW, Sprenger SH, Boerman RH, von Deimling A, Teepen HL, van Overbeeke JJ, Wesseling P (2001) Subtyping of oligo-astrocytic tumors by comparative genomic hybridization. J Pathol 194:81–87

    Article  PubMed  CAS  Google Scholar 

  12. Maintz D, Fiedler K, Koopmann J, Rollbrocker B, Nechev S, Lenartz D, Stangl AP, Louis DN, Schramm J, Wiestler OD, von Deimling A (1997) Molecular genetic evidence for subtypes of oligoastrocytomas. J Neuropathol Exp Neurol 56:1098–1104

    Article  PubMed  CAS  Google Scholar 

  13. Kros JM, van Run PR, Alers JC, Beverloo HB, van den Bent MJ, Avezaat CJ, van Dekken H (1999) Genetic aberrations in oligodendroglial tumors: an analysis using comparative genomic hybridization (CGH). J Pathol 188:282–288

    Article  PubMed  CAS  Google Scholar 

  14. McDonald JM, Ju See S, Tremont IW, Colman H, Gilbert MR, Groves M, Burger PC, Louis DN, Giannini C, Fuller G, Passe S, Blair H, Jenkins RB, Yang H, Ledoux A, Aaron J, Tipnis U, Zhang W, Hess K, Aldape K (2005) The prognostic impact of histology and 1p/19q status in anaplastic oligodendroglial tumors. Cancer 104:1468–1477

    Article  PubMed  CAS  Google Scholar 

  15. Gadji M, Fortin D, Tsanaclis AM, Drouin R (2009) Is the 1p/19q deletion a diagnostic marker of oligodendrogliomas? Cancer Genet Cytogenet 194:12–22

    Article  PubMed  CAS  Google Scholar 

  16. Giannini C, Burger PC, Berkey BA, Cairncross JG, Jenkins RB, Mehta M, Curran WJ, Aldape K (2008) Anaplastic oligodendroglial tumors: refining the correlation among histopathology, 1p 19q deletion and clinical outcome in Intergroup Radiation Therapy Oncology Group Trial 9402. Brain Pathol 18:360–369

    Article  PubMed  Google Scholar 

  17. Ino Y, Betensky RA, Zlatescu MC, Sasaki H, Macdonald DR, Stemmer-Rachamimov AO, Ramsay DA, Cairncross JG, Louis DN (2001) Molecular subtypes of anaplastic oligodendroglioma: implications for patient management at diagnosis. Clin Cancer Res 7:839–845

    PubMed  CAS  Google Scholar 

  18. Ohgaki H, Kleihues P (2009) Genetic alteration and signaling pathway in the evolution of gliomas. Cancer Sci 100:2235–2241

    Article  PubMed  CAS  Google Scholar 

  19. Yan H, Bigner DD, Velculescu V, Parsons DW (2009) Mutant metabolic enzymes are at the origin of gliomas. Cancer Res 69:9157–9159

    Article  PubMed  CAS  Google Scholar 

  20. Lin M, Wei LJ, Sellers WR, Lieberfarb M, Wong WH, Li C, Wong WH, Li C (2004) dChipSNP: significance curve and clustering of SNP array-based loss-of-heterozygosity data. Bioinformatics 20:1233–1240

    Article  PubMed  CAS  Google Scholar 

  21. Li C, Wong WH (2001) Model based analysis of oligonucleotide arrays: expression index computation and outlier detection. Proc Natl Acad Sci USA 98:31–36

    Article  PubMed  CAS  Google Scholar 

  22. Li C, Wong WH (2001) Model based analysis of oligonucleotide arrays: model validation, design issues and standard error application. Genome Biol 2:8–14

    Google Scholar 

  23. Beroukhim R, Ling M, Park Y, Hao K, Zhao X, Garraway LA, Fox E, Hochberg EP, Mellinghoff IK, Hofer MD, Descaceaud A, Rubin MA, Meyerson M, Sellers WR, Li C (2006) Inferring LOH from unpaired tumour using high density oligonucleotide SNP arrays. PLoS Comput Biol 2:e41

    Article  PubMed  Google Scholar 

  24. Zhao X, Li C, Paez G, Chin K, Janne P, Chen TH, Girard L, Minna J, Christiani D, Leo C, Gray JW, Sellers WR (2004) An integrated view of copy number and allelic alterations in the cancer genome using single nucleotide polymorphism arrays. Cancer Res 64:3060–3071

    Article  PubMed  CAS  Google Scholar 

  25. Paulin R, Grigg GW, Davey MW, Pipper AA (1998) Urea improves efficiency of bisulphite-mediated sequencing of 5′-methylcytosine in genomic DNA. Nucleic Acids Res 26:5009–5010

    Article  PubMed  CAS  Google Scholar 

  26. Ehrich M, Nelson MR, Stanssens P, Zabeau M, Liloglou T, Xinarianos G, Cantor CR, Field JK, van den Boom D (2005) Quantitative high-throughput analysis of DNA methylation patterns by base-specific cleavage and mass spectrometry. Proc Natl Acad Sci USA 102:15785–15790

    Article  PubMed  CAS  Google Scholar 

  27. Coolen MW, Statham AL, Gardiner-Garden M, Clark SJ (2007) Genomic profiling of CpG methylation and allelic specificity using quantitative high throughput mass spectroscopy: critical evaluation and improvements. Nucleic Acids Res 35:1–14

    Article  Google Scholar 

  28. Palmisano WA, Divine KK, Saccomanno G, Gilliland FD, Baylin SB, Herman JG, Belinsky SA (2000) Predicting lung cancer by detecting aberrant promoter methylation in sputum. Cancer Res 60:5954–5958

    PubMed  CAS  Google Scholar 

  29. Meyer J, Pusch S, Balss J, Capper D, Mueller W, Christians A, Hartmann C, von Deimling A (2009) PCR- and restriction endonuclease-based detection of IDH1 mutations. Brain Pathol 20:298–300

    Article  PubMed  Google Scholar 

  30. Ueki K, Nishikawa R, Nakazato Y, Hirose T, Hirato J, Funada N, Fujimaki T, Hojo S, Kubo O, Ide T, Usui M, Ochiai C, Ito S, Takahasi H, Mukasa A, Asai A, Kirino T (2002) Correlation of histology and molecular genetic analysis of 1p, 19q, 10q, TP53, EGFR, CDK4 and CDKN2A in 91 astrocytic and oligodendroglial tumors. Clin Cancer Res 8:196–201

    PubMed  CAS  Google Scholar 

  31. Jeuken JMW, Von Deimling A, Wesseling P (2004) Molecular pathogenesis of oligodendroglial tumors. J Neurooncol 70:161–181

    Article  PubMed  Google Scholar 

  32. TCGA (2008) Comprehensive genomic characterization defines human glioblastoma genes and core pathways. Nature 455:1061–1068

    Article  Google Scholar 

  33. Ricard D, Kaloshi G, Amiel-Benouaich A, Lejeune J, Marie Y, Mandonnet E, Kujas M, Mokhtari K, Taillibert S, Laigle-Donadey F, Carpentier AF, Omuro A, Capelle L, Duffau H, Cornu P, Guillevin R, Sanson M, Hoang-Xuan K, Delattre JY (2007) Dynamic history of low grade gliomas before and after temozolomide treatment. Ann Neurol 61:484–490

    Article  PubMed  CAS  Google Scholar 

  34. Bromberg JE, Van den Bent MJ (2009) Oligodendrogliomas: molecular biology and treatment. Oncologist 14:155–163

    Article  PubMed  CAS  Google Scholar 

  35. Mukasa A, Ueki K, Matsumoto S, Tsutsumi S, Nishikawa R, Fujimaki T, Asai A, Kirino T, Aburatani H (2002) Distinction in gene expression profile of oligodendrogliomas with and without allelic loss of 1p. Oncogene 21:3961–3968

    Article  PubMed  CAS  Google Scholar 

  36. Ducray F, Idbaih A, Reyniès A, Bièche I, Thillet J, Mokhtari K, Lair S, Marie Y, Paris S, Vidaud M, Hoang-Xuan K, Delattre O, Delattre JY, Sanson M (2008) Anaplastic oligodendrogliomas with 1p19q codeletion have a proneural gene expression profile. Mol Cancer 7:1–17

    Article  Google Scholar 

  37. Benetkiewicz M, Idbaih A, Cousin P, Boisselier B, Marie Y, Criniere E, Hoang-Xuan K, Delattre JY, Sanson M, Delattre O (2009) NOTCH2 is neither rearranged nor mutated in t(1;19) positive oligodendrogliomas. PLoS ONE 4:e4107

    Article  PubMed  Google Scholar 

  38. Zlatescu MC, Yazdi A, Sasaki H, Megyesi J, Betensky RA, Louis DN, Cairncross JG (2001) Tumor location and growth pattern correlate with genetic signature in oligodendroglial neoplasms. Cancer Res 61:6713–6715

    PubMed  CAS  Google Scholar 

  39. Beroukhim R, Getz G, Nghiemphu L, Barretina J, Hsueh T, Linhart D, Vivanco I, Lee JC, Huang JH, Alexander S, Du J, Kau T, Thomas RK, Shah K, Soto H, Perner S, Prensner J, Debiasi RM, Demichelis F, Hatton C, Rubin MA, Garraway LA, Nelson SF, Liau L, Mischel PS, Cloughesy TF, Meyerson M, Golub TA, Lander ES, Mellinghoff IK, Sellers WR (2007) Assessing the significance of chromosomal aberrations in cancer: methodology and application to glioma. Proc Natl Acad Sci USA 104:20007–20012

    Article  PubMed  CAS  Google Scholar 

  40. Esteller M, Garcia-Foncillas J, Andion E, Goodman SN, Hidalgo OF, Vanaclocha V, Baylin SB, Herman JG (2000) Inactivation of the DNA-repair gene MGMT and the clinical response of gliomas to alkylating agents. N Engl J Med 343:1350–1354

    Article  PubMed  CAS  Google Scholar 

  41. Dong SM, Pang JC, Poon WS, Hu J, To KF, Chang AR, Ng HK (2001) Concurrent hypermethylation of multiple genes is associated with grade of oligodendroglial tumors. J Neuropathol Exp Neurol 60:808–816

    PubMed  CAS  Google Scholar 

  42. Möllemann M, Wolter M, Felsberg J, Collins VP, Reifenberger G (2005) Frequent promoter hypermethylation and low expression of the MGMT gene in oligodendroglial tumors. Int J Cancer 113:379–385

    Article  PubMed  Google Scholar 

  43. Brandes AA, Tosoni A, Cavallo G, Reni M, Franceschi E, Bonaldi L, Bertorelle R, Gardiman M, Ghimenton C, Iuzzolino P, Pession A, Blatt V, Herman M (2006) Correlations between O6-methylguanine DNA methyltransferase promoter methylation status, 1p and 19q deletions, and response to temozolomide in anaplastic and recurrent oligodendroglioma: a prospective GICNO study. J Clin Oncol 24:4746–4753

    Article  PubMed  CAS  Google Scholar 

  44. Nutt CL, Noble M, Chambers AF, Cairncross JG (2000) Differential expression of drug resistance genes and chemosensitivity in glial cells lineages correlate with differential response of oligodendrogliomas and astrocitomas to chemotherapy. Cancer Res 60:4812–4818

    PubMed  CAS  Google Scholar 

  45. Dang L, White D, Gross S (2009) Cancer-associated IDH1 mutations produce 2-hydroxyglutarate. Nature 462:739–747

    Article  PubMed  CAS  Google Scholar 

  46. Bleeker F, Atai N, Lamba S, Jonker A, Rijkeboer D, Bosch K, Tigchelaar W, Troost D, Vandertop W, Bardelli A, Van Noorden C (2010) The prognostic IDH1R132 mutation is associated with reduced NAP+-dependent IDH activity in glioblastoma. Acta Neuropathol [Epub ahead of print]

  47. Bredel M, Scholtens D, Harsh G, Bredel C, Chandler J, Renfrow J, Yadav A, Vogel H, Scheck A, Tibshirani R, Sikic B (2009) A network model of a cooperative genetic landscape in brain tumours. JAMA 302:261–275

    Article  PubMed  CAS  Google Scholar 

  48. Kotliarov Y, Steed M, Christopher N, Walling J, Su Q, Center A, Heiss J, Rosenblum M, Mikkelsen T, Zenklusen J, Fine H (2006) High-resolution global genomic survey of 178 gliomas reveals novel regions of copy number alteration and allelic imbalances. Cancer Res 66:9428–9436

    Article  PubMed  CAS  Google Scholar 

  49. Kotliarov Y, Kotliarova S, Charong N, Li A, Walling J, Aquilanti E, Ahn S, Steed M, Su Q, Center A, Zenklusen J, Fine H (2009) Correlation analysis between single-nucleotide polymorphism and expression arrays in gliomas identifies potentially relevant target genes. Cancer Res 69:596–603

    Article  Google Scholar 

Download references

Acknowledgments

The authors wish to thank members of the UCIM, Dr. E. Serna and E. Buso for their technical assistance. This study was supported by grants from European project eTUMOUR (FP6-2002-LIFESCIHEALTH 503094), Spanish Government project SAF2007-6547 and project FLENI 49/06.

Author information

Authors and Affiliations

  1. Department of Physical-Chemistry, Universitat de Valencia, Dr. Moliner sn, 46100, Burjassot, Valencia, Spain

    Rubén Ferrer-Luna & Bernardo Celda

  2. Department of Neuropathology, FLENI, Montañeses 2325, C1428AQK, Buenos Aires, Argentina

    Lina Núñez, Eugenia Arias, Naomi Arakaki, Gustavo Sevlever & Horacio Martinetto

  3. Neurosurgery Service, Hospital de la Ribera-Alzira, Valencia, Spain

    José Piquer

  4. Research Foundation, Hospital Clínico Universitario, Valencia, Spain

    Francisco Dasí

  5. Department of Neurosurgery, FLENI, Montañeses 2325, C1428AQK, Buenos Aires, Argentina

    Andrés Cervio

  6. CIBER BBN, ISC-III, Valencia, Spain

    Bernardo Celda

Authors
  1. Rubén Ferrer-Luna
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Lina Núñez
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. José Piquer
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Eugenia Arias
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Francisco Dasí
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Andrés Cervio
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Naomi Arakaki
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Gustavo Sevlever
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Bernardo Celda
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. Horacio Martinetto
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Horacio Martinetto.

Electronic supplementary material

Rights and permissions

Reprints and permissions

About this article

Cite this article

Ferrer-Luna, R., Núñez, L., Piquer, J. et al. Whole-genomic survey of oligodendroglial tumors: correlation between allelic imbalances and gene expression profiles. J Neurooncol 103, 71–85 (2011). https://doi.org/10.1007/s11060-010-0369-4

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11060-010-0369-4

Keywords

Search

Navigation