Skip to main content
PMC home page
Brain Pathology logoLink to Brain Pathology
. 2006 Apr 5;14(1):34–42. doi: 10.1111/j.1750-3639.2004.tb00495.x

Selective Expression of a Subset of Neuronal Genes in Oligodendroglioma with Chromosome 1p Loss

Akitake Mukasa 1,2,†, Keisuke Ueki 4,✉, Xijin Ge 1, Shumpei Ishikawa 1,3, Takafumi Ide 5, Takamitsu Fujimaki 6, Ryo Nishikawa 7, Akio Asai 8, Takaaki Kirino 2, Hiroyuki Aburatani 1
PMCID: PMC8095850  PMID: 14997935

Abstract

Gliomas are classified based mainly on microscopic resemblance to their presumed glial origin such as astrocyte and oligodendrocyte. However, more objective diagnostic criteria are indispensable for the precise treatment of patients. For instance, loss of the short arm of chromosome 1 (1p) in oligodendrogliomas is recognized as an important marker for better response to chemotherapy and longer survival of the patients. To gain insight into their molecular biological background and to identify genes characterizing each subgroup, we investigated gene expression profile of the 4 glioma subsets, oligodendroglioma with and without 1p loss, diffuse astrocytoma and glioblastoma using DNA microarray. Remarkably, most of the genes showing distinctive expression in oligodendroglioma with 1p loss were also highly expressed in normal brain tissues and had neuron‐related function, which included MYT1L, INA, RIMS2, SNAP91 and SNCB. Histological analysis also demonstrated that MYT1L, which were abundantly expressed in normal neuron, were certainly present in tumor cells. These results suggest that oligodendroglioma, especially with 1p loss, has more or less neuronal characteristics although oligodendroglioma is thought to originate form glial lineage cell. With further pathological studies, those neuron‐related genes might be good diagnostic markers for oligodendroglioma of better prognosis as well.

Full Text

The Full Text of this article is available as a PDF (676.9 KB).

References

  • 1. Cairncross JG , Ueki K , Zlatescu MC , Lisle DK , Finkelstein DM , Hammond RR , Silver JS , Stark PC , Macdonald DR , Ino Y , Ramsay DA , Louis DN ( 1998. ) Specific genetic predictors of chemotherapeutic response and survival in patients with anaplastic oligodendrogliomas . J natl cancer lnst 90 : 1473 – 1479 . [DOI] [PubMed] [Google Scholar]
  • 2. Clayton DF , George JM ( 1998. ) The synucleins: a family of proteins involved in synaptic function, plasticity, neurodegeneration and disease . Trends Neurosci 21 : 249 – 254 . [DOI] [PubMed] [Google Scholar]
  • 3. Eisen MB , Spellman PT , Brown PO , Botstein D ( 1998. ) Cluster analysis and display of genomewide expression patterns Proc Natl Acad Sci U S A 95 : 14863 – 14868 . [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 4. Fuller GN , Rhee CH , Hess KR , Caskey LS , Wang R , Bruner JM , Yung WK , Zhang W ( 1999. ) Reactivation of insulin‐like growth factor binding protein 2 expression in glioblastoma multiforme: a revelation by parallel gene expression profiling . Cancer 59 : 4228 – 4232 . [PubMed] [Google Scholar]
  • 5. Golub TR , Slonim DK , Tamayo P , Huard C , Gaasenbeek M , Mesirov JP , Coller H , Loh ML , Downing JR , Caligiuri MA , Bloomfield CD , Lander ES ( 1999. ) Molecular classification of cancer: class discovery and class prediction by gene expression monitoring . Science 286 : 531 – 537 . [DOI] [PubMed] [Google Scholar]
  • 6. Gutmann DH , Hedrick NM , Li J , Nagarajan R , Perry A , Watson MA ( 2002. ) Comparative gene expression profile analysis of neurofibromatosis 1‐associated and sporadic pilocytic astrocytomas Cancer Res 62 : 2085 – 2091 . [PubMed] [Google Scholar]
  • 7. Huang H , Colella S , Kurrer M , Yonekawa Y , Kleihues P , Ohgaki H ( 2000. ) Gene expression profiling of low‐grade diffuse astrocytomas by cDNA arrays . Cancer Res 60 : 6868 – 6874 . [PubMed] [Google Scholar]
  • 8. 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] [Google Scholar]
  • 9. Ishii M , Hashimoto S , Tsutsumi S , Wada Y , Matsushima K , Kodama T , Aburatani H ( 2000. ) Direct comparison of GeneChip and SAGE on the quantitative accuracy in transcript profiling analysis . Genomics 68 : 136 – 143 . [DOI] [PubMed] [Google Scholar]
  • 10. Kim JG , Armstrong RCV , Agosoton D , Robinsky A , Wiese C , Nagle J , Hudson LD ( 1997. ) Myelin transcription factor 1 (Myt1) of the oligodendrocyte lineage, along with a closely related CCHC Zinc finger, is expressed in developing neurons in the mammalian central nervous system . J Neuro Sci Res 50 : 272 – 290 . [DOI] [PubMed] [Google Scholar]
  • 11. Kleihues P , Cavenee WK ( eds. ) ( 2000. ) Pathology and Genetics of Tumours of the Nervous System . IARC press; , Lyon . [Google Scholar]
  • 12. Lu QR , Park JK , Noll E , Chan JA , Alberta J , Yuk D , Alzmora MG , Louis DN , Stiles CD , Rowitch DH , Black PM ( 2001. ) Oligodendrocyte lineage genes (OLIG) as molecular markers for human glial brain tumors . Proc Natl Acad Sci U S A 98 : 10851 – 10856 . [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 13. Lu QR , Sun T , Zhu Z , Ma N , Garcia M , Stiles CD , Rowitch DH ( 2002. ) Common developmental requirement for Olig function indicates a motor neuron/oligodendrocyte connection . Cell 109 : 75 – 86 . [DOI] [PubMed] [Google Scholar]
  • 14. Marie Y , Sanson M , Mokhtari K , Leuraud P , Kujas M , Delattre JY , Poirier J , Zalc B , Hoang‐Xuan K ( 2001. ) OLIG2 as a specific marker of oligodendroglial tumour cells . Lancet 358 : 298 – 300 . [DOI] [PubMed] [Google Scholar]
  • 15. McGraw TS , Mickle JP , Shaw G , Streit WJ ( 2002. ) Axonally transported peripheral signals regulatealpha‐internexin expression in regenerating motoneurons . J Neurosci 22 : 4955 – 4963 . [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 16. Mukasa A , Ueki K , Matsumoto S , Tsutsumi Nishikawa R , Fujimaki T , Asai A , Kirino T , Aburatani H ( 2002. ) Distinction in gene expression profiles of oligodendrogliomas with and without allelic loss of 1p . Oncogene 21 : 3961 – 3968 . [DOI] [PubMed] [Google Scholar]
  • 17. 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] [Google Scholar]
  • 18. Patt S , Labrakakis C , Bernstein M , Weydt P , Cervos‐Navarro J , Nisch G , Kettenmann H ( 1996. ) Neuron‐like physiological properties of cells from human oligodendroglial tumors . Neuroscience 71 : 601 – 611 . [DOI] [PubMed] [Google Scholar]
  • 19. Perry A , Scheithauer BW , Macaulay RJ , Raffel C , Roth KA , Kros JM ( 2002. ) Oligodendrogliomas with neurocytic differentiation. A report of 4 cases with diagnostic and histogenetic implications . J Neuropathol Exp Neurol 61 : 947 – 955 . [DOI] [PubMed] [Google Scholar]
  • 20. Rickman DS , Bobek MP , Misek DE , Kuick R , Blaivas M , Kurnit DM , Taylor J , Hanash SM ( 2001. ) Distinctive molecular profiles of high‐grade and low‐grade gliomas based on oligonucleotide microarray analysis . Cancer Res 61 : 6885 – 6891 . [PubMed] [Google Scholar]
  • 21. Sallinen SL , Sallinen PK , Haapasalo HK , Helin HJ , Helen PT , Schraml P , Kallioniemi OP , Kononen J ( 2000. ) Identification of defferentially expressed genes in human gliomas by DNA microarray and tissue chip techniques . Cancer Res 60 : 6617 – 6622 . [PubMed] [Google Scholar]
  • 22. Su AI , Cooke MP , Ching KA , Hakak Y , Walker JR , Wiltshire T , Orth AP , Vega RG , Sapinoso LM , Moqrich A , Patapoutian A , Hampton GM , Schultz PG , Hogenesch JB ( 2002. ) Large‐scale analysis of the human and mouse transcriptomes . Proc Natl Acad Sci S A 99 : 4465 – 4470 . [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 23. Tusher VG , Tibshirani R , Chu G ( 2001. ) Significance analysis of microarrays applied to the ionizing radiation response . Proc Natl Acad S A 98 : 5116 – 5121 . [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 24. 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 , Takahashi H , Mukasa A , Asai A , Kerino 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] [Google Scholar]
  • 25. Watson MA , Perry A , Budhjara V , Hicks C , Shannon WD , Rich KM ( 2001. ) Gene expression profiling with oligonucleotide microarrays distinguishes World Health Organization grade of oligodendrogliomas . Cancer Res 61 : 1825 – 1829 . [PubMed] [Google Scholar]
  • 26. Wharton SB , Chan KK , Hamilton FA , Anderson JR ( 1998. ) Expression of neuronal markers in oligodendrogliomas: an immunogistochemical study . Neuropathol Appl Neurobiol 24 : 302 – 308 . [DOI] [PubMed] [Google Scholar]
  • 27. Wolf HK , Buslei R , Blumcke I , Wiestler OD , Pietsch T ( 1997. ) Neural antigens in oligodendrogliomas and dysembryoplastic neuroepithelial tumors . Acta Neuropathol (Berl) 94 : 436 – 443 . [DOI] [PubMed] [Google Scholar]
  • 28. Zhou Q , Anderson DJ ( 2002. ) The bHLH transcription factors OLIG2 and OLIG1 couple neuronal and glial subtype specification . Cell 109 : 61 – 73 . [DOI] [PubMed] [Google Scholar]

Articles from Brain Pathology are provided here courtesy of Wiley

RESOURCES