Skip to main content

Advertisement

SpringerLink
Log in

Identification of differentially expressed genes in human pineal parenchymal tumors by microarray analysis

  • Regular Paper
  • Published:
Acta Neuropathologica Aims and scope Submit manuscript

Abstract

Human pineal parenchymal tumors (PPTs) are rare tumors, and little is known about their molecular pathogenesis. We used Atlas plastic human 8 K microarray analysis to identify the genes expressed in four human PPTs of different grades, in normal brain tissue and in a normal fetal pineal gland. We selected the most highly expressed genes in PPT (n=39) and compared their expression to that both in normal brain and fetal pineal gland. Nine genes were expressed more than twice as strongly and 3 at about half the level in PPT. Furthermore, real-time reverse transcription-PCR was performed to compare mRNA levels in the four PPTs, in four medulloblastomas (MBs) (the most common type of similar embryonal neoplasm in the cerebellum), and in normal brain, for 9 of the 39 genes. Among genes showing an expression similar to that obtained with microarray, puromycin-sensitive aminopeptidase and teratocarcinoma-derived growth factor 3 were up-regulated in PPT and in MB, and adenomatous polyposis coli like was down-regulated only in PPT. Up-regulated expression of chromosome 17 open reading frame 1A was seen in high-grade PPT and in MB, but not in lower grade PPT. In conclusion, our results identified a number of genes that are differentially expressed in PPT and MB, and some of them may serve as prognostic markers and can be used to define mechanisms of tumorigenesis.

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. Aldosari N, Rasheed BK, McLendon RE, Friedman HS, Bigner DD, Bigner SH (2000) Characterization of chromosome 17 abnormalities in medulloblastomas. Acta Neuropathol 99:345–351

    Article  Google Scholar 

  2. Bastianelli E, Pochet R (1995)Calbindin-D28k, calretinin, and S-100 immunoreactivities in rat pineal gland during postnatal development. J Pineal Res 18:127–134

    Google Scholar 

  3. Bello MJ, Rey JA, Campos JM de, Kusak ME (1993) Chromosomal abnormalities in a pineocytoma. Cancer Genet Cytogenet 71:185–186

    Article  Google Scholar 

  4. Brockmeyer DL, Walker ML, Thompson G, Fults DW (1997) Astrocytoma and pineoblastoma arising sequentially in the fourth ventricle of the same patient. Case report and molecular analysis. Pediatr Neurosurg 26:36–40

    Google Scholar 

  5. Champier J, Jouvet A, Rey C, Guyotat J, Fevre-Montange M (2003) Differential somatostatin receptor subtype expression in human normal pineal gland and pineal parenchymal tumors. Cell Mol Neurobiol 23:101–113

    Article  Google Scholar 

  6. Constam DB, Tobler AR, Rensing-Ehl A, Kemler I, Hersh LB, Fontana A (1995) Puromycin-sensitive aminopeptidase. Sequence analysis, expression, and functional characterization. J Biol Chem 270:26931–26939

    Article  Google Scholar 

  7. Dario A, Cerati M, Taborelli M, Finzi G, Pozzi M, Dorizzi A (2000) Cytogenetic and ultrastructural study of a pineocytoma case report. J Neurooncol 48:131–134

    Article  Google Scholar 

  8. Ellison D (2002) Classifying the medulloblastoma: insights from morphology and molecular genetics. Neuropathol Appl Neurobiol 28:257–282

    Article  CAS  PubMed  Google Scholar 

  9. Fischer H, Stenling R, Rubio C, Lindblom A (2001) Differential expression of aquaporin 8 in human colonic epithelial cells and colorectal tumors. BMC Physiology 1:1

    Article  Google Scholar 

  10. Hlubek F, Spaderna S, Jung A, Kirchner T, Brabletz T (2004) Beta-catenin activates a coordinated expression of the proinvasive factors laminin-5 gamma2 chain and MT1-MMP in colorectal carcinomas. Int J Cancer 108:321–326

    Article  CAS  PubMed  Google Scholar 

  11. Hong SH, Nah HY, Lee JY, Gye MC, Kim CH, Kim MK (2004) Analysis of estrogen-regulatd genes in mouse uterus using cDNA microarray and laser capture microdissection. J Endocrinol 181:157–167

    Article  Google Scholar 

  12. Honore B (2000) The hnRNP 2H9 gene, which is involved in the splicing reaction, is a multiply spliced gene. Biochim Biophys Acta 1492:108–119

    Google Scholar 

  13. Hsieh CM, Fukumoto S, Layne MD, Maemura K, Charles H, Patel A, Perrella MA, Lee ME (2000) Striated muscle preferentially expressed genes alpha and beta are two serine/threonine protein kinases derived from the same gene as the aortic preferentially expressed gene-1. J Biol Chem 275:36966–36973

    Article  Google Scholar 

  14. Huang H, Mahler-Araujo BM, Sankila A, Chimelli L, Yonekawa Y, Kleihues P, Ohgaki H (2000) APC mutations in sporadic medulloblastomas. Am J Pathol 156:433–437

    CAS  PubMed  Google Scholar 

  15. Jean S, Bideau C, Bellon L, Halimi G, De Meo M, Orsiere T, Dumenil G, Berge-Lefranc JL, Botta A (2001) The expression of genes induced in melanocytes by exposure to 365-nm UVA: study by cDNA arrays and real-time quantitative RT-PCR. Biochim Biophys Acta 1522:89–96

    Google Scholar 

  16. Jouvet A, Fevre-Montange M, Besancon R, Derrington E, Saint-Pierre G, Belin MF, Pialat J, Lapras C (1994) Structural and ultrastructural characteristics of human pineal gland, and pineal parenchymal tumors. Acta Neuropathol 88:334–348

    Google Scholar 

  17. Jouvet A, Saint-Pierre G, Fauchon F, Privat K, Bouffet E, Ruchoux MM, Chauveinc L, Fevre-Montange M (2000) Pineal parenchymal tumors: a correlation of histological features with prognosis in 66 cases. Brain Pathol 10:49–60

    CAS  PubMed  Google Scholar 

  18. Kees UR, Biegel JA, Ford J, Ranford PR, Peroni SE, Hallam LA, Parmiter AH, Willoughby ML, Spagnolo D (1994) Enhanced MYCN expression and isochromosome 17q in pineoblastoma cell lines. Genes Chromosomes Cancer 9:129–135

    Google Scholar 

  19. Kees UR, Spagnolo D, Hallam LA, Ford J, Ranford PR, Baker DL, Callen DF, Biegel JA (1998) A new pineoblastoma cell line, PER-480, with der(10)t(10;17), der(16)t(1;16), and enhanced MYC expression in the absence of gene amplification. Cancer Genet Cytogenet 100:159–164

    Article  Google Scholar 

  20. Kennerson ML, Nassif NT, Nicholson GA (1998) Genomic structure and physical mapping of C17orf1: a gene associated with the proximal element of the CMT1A-REP binary repeat. Genomics 53:110–112

    Article  Google Scholar 

  21. Kleihues P, Burger PC, Scheithauer BW (1993) The new WHO classification of brain tumours. Brain Pathol 3 :255–268

    Google Scholar 

  22. Lastowska M, Cotterill S, Bown N, Cullinane C, Variend S, Lunec J, Strachan T, Pearson AD, Jackson MS (2002) Breakpoint position on 17q identifies the most aggressive neuroblastoma tumors. Genes Chromosomes Cancer 34:428–436

    Article  Google Scholar 

  23. Lau WY, Lai PB, Leung MF, Leung BC, Wong N, Chen G, Leung TW, Liew CT (2000) Differential gene expression of hepatocellular carcinoma using cDNA microarray analysis. Oncol Res 12:59–69

    Article  Google Scholar 

  24. Ljubimova JY, Lakhter AJ, Loksh A, Yong WH, Riedinger MS, Miner JH, Sorokin LM, Ljubimov AV, Black KL (2001) Overexpression of alpha4 chain-containing laminins in human glial tumors identified by gene microarray analysis. Cancer Res 61:5601–5610

    Google Scholar 

  25. Mena H, Nakazato Y, Jouvet A, Sheithauer BW (2000) Pineal parenchymal tumours. In: Kleihues P, Cavenee CW (eds) Pathology and genetics tumours of the nervous system. IARC Press, Lyon, pp 115–121

  26. Michiels EM, Oussoren E, Van Groenigen M, Pauws E, Bossuyt PM, Voute PA, Baas F. (1999) Genes differentially expressed in medulloblastoma and fetal brain. Physiol Genomics 1:83–91

    Google Scholar 

  27. Morkel M, Huelsken J, Wakamiya M, Ding J, Wetering M van de, Clevers H, Taketo MM, Behringer RR, Shen MM, Birchmeier W (2003) Beta-catenin regulates Cripto- and Wnt3-dependent gene expression programs in mouse axis and mesoderm formation. Development 130:6283–6294

    Article  Google Scholar 

  28. Nakagawa H, Koyama K, Monden M, Nakamura Y (1999) Analysis of APCL, a brain-specific adenomatous polyposis coli homologue, for mutations and expression in brain tumors. Jpn J Cancer Res 90:982–986

    Google Scholar 

  29. Nakagawa H, Koyama K, Murata Y, Morito M, Akiyama T, Nakamura Y (2000) APCL, a central nervous system-specific homologue of adenomatous polyposis coli tumor suppressor, binds to p53-binding protein 2 and translocates it to the perinucleus. Cancer Res 60:101–105

    Google Scholar 

  30. Nakagawa H, Murata Y, Koyama K, Fujiyama A, Miyoshi Y, Monden M, Akiyama T, Nakamura Y (1998) Identification of a brain-specific APC homologue, APCL, and its interaction with beta-catenin. Cancer Res 58:5176–5181

    Google Scholar 

  31. Nozaki M, Tada M, Matsumoto R, Sawamura Y, Abe H, Iggo RD (1998) Rare occurrence of inactivating p53 gene mutations in primary non-astrocytic tumors of the central nervous system: reappraisal by yeast functional assay. Acta Neuropathol 95:291–296

    Article  Google Scholar 

  32. Pomeroy SL, Tamayo P, Gaasenbeek M, Sturla LM, Angelo M, McLaughlin ME, Kim JY, Goumnerova LC, Black PM, Lau C, Allen JC, Zagzag D, Olson JM, Curran T, Wetmore C, Biegel JA, Poggio T, Mukherjee S, Rifkin R, Califano A, Stolovitzky G, Louis DN, Mesirov JP, Lander ES, Golub TR (2002) Prediction of central nervous system embryonal tumour outcome based on gene expression. Nature 415:436–442

    CAS  PubMed  Google Scholar 

  33. Rainho CA, Rogatto SR, Moraes LC de, Barbieri-Neto J (1992) Cytogenetic study of a pineocytoma. Cancer Genet Cytogenet 64:127–132

    Article  Google Scholar 

  34. Rickert CH, Simon R, Bergmann M, Dockhorn-Dworniczak B, Paulus W (2001) Comparative genomic hybridization in pineal parenchymal tumors. Genes Chromosomes Cancer 30:99–104

    Article  Google Scholar 

  35. 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

    Google Scholar 

  36. Sallinen SL, Sallinen PK, Haapasalo HK, Helin HJ, Helen PT, Schraml P, Kallioniemi OP, Kononen J (2000) Identification of differentially expressed genes in human gliomas by DNA microarray and tissue chip techniques. Cancer Res 60:6617–6622

    Google Scholar 

  37. Sawyer JR, Sammartino G, Husain M, Linskey ME (2003) Constitutional t(16;22)(p13.3;q11.2 approximately 12) in a primitive neuroectodermal tumor of the pineal region. Cancer Genet Cytogenet 142:73–76

    Article  Google Scholar 

  38. Scarlett CO, Blackshear PJ (2003) Neuroanatomical development in the absence of PKC phosphorylation of the myristoylated alanine-rich C-kinase substrate (MARCKS) protein. Dev Biol Res 144:25–42

    Article  Google Scholar 

  39. Shen MM (2003) Decrypting the role of Cripto in tumorigenesis. J Clin Invest 112:500–502

    Article  Google Scholar 

  40. Shimizu N, Ohta M, Fujiwara C, Sagara J, Mochizuki N, Oda T, Utiyama H (1991) Expression of a novel immediate early gene during 12-O-tetradecanoylphorbol-13-acetate-induced macrophagic differentiation of HL-60 cells. J Biol Chem 266:12157–12161

    CAS  PubMed  Google Scholar 

  41. Sreekantaiah C, Jockin H, Brecher ML, Sandberg AA (1989) Interstitial deletion of chromosome 11q in a pineoblastoma. Cancer Genet Cytogenet 39:125–131

    Article  Google Scholar 

  42. Takano K, Nakamoto T, Okajima M, Sudo A, Uetake K, Saitoh S (2003) Cerebellar and brainstem involvement in familial juvenile nephronophthisis type I. Pediatr Neurol 28:142–144

    Article  Google Scholar 

  43. Thompson MW, Tobler A, Fontana A, Hersh LB (1999) Cloning and analysis of the gene for the human puromycin-sensitive aminopeptidase. Biochem Biophys Res Commun 258:234–240

    Article  Google Scholar 

  44. Tobler AR, Constam DB, Schmitt-Graff A, Malipiero U, Schlapbach R, Fontana A (1997) Cloning of the human puromycin-sensitive aminopeptidase and evidence for expression in neurons. J Neurochem 68:889–897

    Google Scholar 

  45. Tsumanuma I, Sato M, Okazaki H, Tanaka R, Washiyama K, Kawasaki T, Kumanishi T (1995) The analysis of p53 tumor suppressor gene in pineal parenchymal tumors. Noshuyo Byori 12:39–43

    Google Scholar 

  46. Tsumanuma I, Tanaka R, Ichikawa T, Washiyama K, Kumanishi T (2000) Demonstration of hydroxyindole-O-methyltransferase (HIOMT) mRNA expression in pineal parenchymal tumors: histochemical in situ hybridization. J Pineal Res 28:203–209

    Article  Google Scholar 

  47. Van Es JH, Kirkpatrick C, Wetering M van de, Molenaar M, Miles A, Kuipers J, Destree O, Peifer M, Clevers H (1999) Identification of APC2, a homologue of the adenomatous polyposis coli tumour suppressor. Curr Biol 9:105–108

    Article  Google Scholar 

  48. Van Meir EG (1998) “Turcot’s syndrome”: phenotype of brain tumors, survival and mode of inheritance. Int J Cancer 75:162–164

    Article  CAS  PubMed  Google Scholar 

  49. Willis S, Hutchins AM, Hammet F, Ciciulla J, Soo WK, White D, Van der Spek P, Henderson MA, Gish K, Venter DJ, Armes JE (2003) Detailed gene copy number and RNA expression analysis of the 17q12–23 region in primary breast cancers. Genes Chromosomes Cancer 36:382–392

    Article  Google Scholar 

  50. Yamane Y, Mena H, Nakazato Y (2002) Immunohistochemical characterization of pineal parenchymal tumors using novel monoclonal antibodies to the pineal body. Neuropathology 22:66–76

    Article  Google Scholar 

Download references

Acknowledgements

We are greatly indebted to Neurobiotec and to the neurosurgeons, especially J. Guyotat and C. Mottolese, at the Hôpital Neurocardiologique et Neurochirurgical Pierre Wertheimer, Lyon, for supplying the tumor samples. We also thank T. Barkas for linguistic help, and the Centre d’Imagerie de Laennec (CECIL) for the use of the FLA-8000 Image Analyzer. This work was supported by INSERM, the Association of Cancer Research (ARC 3277), and the Ligue Nationale contre le Cancer (185–2002).

Author information

Authors and Affiliations

  1. INSERM U433, Faculté de Médecine RTH Laennec, 69372, Lyon Cedex 08, France

    Jacques Champier, Arlette Bernard & Michelle Fèvre-Montange

  2. Hôpital Neurologique, BP Lyon Montchat, 69394, Lyon Cedex 03, France

    Anne Jouvet

  3. Institut Fédératif des Neurosciences de Lyon, 69394, Lyon Cedex 03, France

    Catherine Rey

  4. INSERM U499, Faculté de Médecine RTH Laennec, 69372, Lyon Cedex 08, France

    Virginie Brun

Authors
  1. Jacques Champier
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Anne Jouvet
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Catherine Rey
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Virginie Brun
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Arlette Bernard
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Michelle Fèvre-Montange
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Jacques Champier.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Champier, J., Jouvet, A., Rey, C. et al. Identification of differentially expressed genes in human pineal parenchymal tumors by microarray analysis. Acta Neuropathol 109, 306–313 (2005). https://doi.org/10.1007/s00401-004-0964-6

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00401-004-0964-6

Keywords

Search

Navigation