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Genetic analysis of human glioblastomas using a genomic microarray system

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Abstract

Genomic microarray systems can simultaneously provide substantial genetic and chromosomal information in a relatively short time. We have analyzed genomic DNA from frozen sections of 30 cases of primary glioblastomas by GenoSensor Array 300 in order to characterize gene amplifications, gene deletions, and chromosomal information in the whole genome. Genes that were frequently amplified includedPFC2/CYLN2 (63.3%),EGFR (53.3%),IL6 (53.3%),ABCB1 (MDR1) (36.7%), andPDGFRA (26.7%). Genes that were frequently deleted includedFGFR2 (66.7%),MTAP (60.0%),DMBT1 (56.7%),CDKN2A (p16)/MTAP (50.0%),PIK3CA (43.3%), andEGR2 (43.3%), but deletion ofRB1 orTP53 was rarely detected. Chromosomal gains were observed frequently for 7q (33.3%), 7p (20.0%), and 17q (13.3%). Loss of the 10q was frequently detected in 13 of 30 cases (46.7%). Loss of the entire chromosome 10 was seen in 9 of 30 cases (30.0%), and was often accompanied byEGFR amplification (7 cases, 77.8%). The GenoSensor Array 300 proved to be useful for identification of genome-wide molecular changes in glioblastomas. The obtained microarray profile can also yield valuable insight into the molecular events underlying carcinogenesis of brain tumors and may provide clues about clinical correlations, including response to treatment.

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References

  1. Cairncross JG, Ueki K, Zlatescu MC, et al, (1998) Specific genetic predictors of chemotherapeutic response and survival in patients with anaplastic oligodendrogliomas. J Natl Cancer Inst 90:1473–1479

    Article  PubMed  CAS  Google Scholar 

  2. Daigo Y, Chin SF, Gorringe KL, et al, (2001) Degenerate oligonucleotide primed-polymerase chain reaction-based array comparative genomic hybridization for extensive amplicon profiling of breast cancers: a new approach for the molecular analysis of paraffin-embedded cancer tissue. Am J Pathol 158:1623–1631

    PubMed  CAS  Google Scholar 

  3. Zhao J, Roth J, Bode-Lesniewska B, et al, (2002) Combined comparative genomic hybridization and genomic microarray for detection of gene amplifications in pulmonary artery intimal sarcomas and adrenocortical tumors. Genes Chromosomes Cancer 34:48–57

    Article  PubMed  CAS  Google Scholar 

  4. Hori Y, Hori H, Yamada Y, et al, (1998) The methylthioadenosine phosphorylase gene is frequently co-deleted with the p16INK4a gene in acute type adult T-cell leukemia. Int J Cancer 75:51–56

    Article  PubMed  CAS  Google Scholar 

  5. Maruno M, Ninomiya H, Ghulam Muhammad AK, et al, (2000) Whole-genome analysis of human astrocytic tumors by comparative genomic hybridization. Brain Tumor Pathol 17:21–27

    Article  PubMed  CAS  Google Scholar 

  6. Maruno M, Yoshimine T, Muhammad AK, et al, (1999) Chromosomal aberrations detected by comparative genomic hybridization (CGH) in human astrocytic tumors. Cancer Lett 135:61–66

    Article  PubMed  CAS  Google Scholar 

  7. Batova A, Diccianni MB, Nobori T, et al, (1996) Frequent deletion in the methylthioadenosine phosphorylase gene in T-cell acute lymphoblastic leukemia: strategies for enzyme-targeted therapy. Blood 88:3083–3090

    PubMed  CAS  Google Scholar 

  8. Solinas-Toldo S, Lampel S, Stilgenbauer S, et al, (1997) Matrix-based comparative genomic hybridization: biochips to screen for genomic imbalances. Genes Chromosomes Cancer 20:399–407

    Article  PubMed  CAS  Google Scholar 

  9. Pinkel D, Segraves R, Sudar D, et al (1998) High resolution analysis of DNA copy number variation using comparative genomic hybridization to microarrays. Nat Genet 20:207–211

    Article  PubMed  CAS  Google Scholar 

  10. Heiskanen MA, Bittner ML, Chen Y, et al, (2000) Detection of gene amplification by genomic hybridization to cDNA microarrays. Cancer Res 60:799–802

    PubMed  CAS  Google Scholar 

  11. Gray SG, Kytola S, Lui WO, et al, (2000) Modulating IGFBP-3 expression by trichostatin A: potential therapeutic role in the treatment of hepatocellular carcinoma. Int J Mol Med 5:33–41

    PubMed  CAS  Google Scholar 

  12. Maruno M, Yoshimine T, Muhammad AK, et al (1996) Loss of heterozygosity of microsatellite loci on chromosome 9p in astrocytic tumors and its prognostic implications. J Neurooncol 30:19–24

    Article  PubMed  CAS  Google Scholar 

  13. von Deimling A, Louis DN, von Ammon K, et al (1992) Association of epidermal growth factor receptor gene amplification with loss of chromosome 10 in human glioblastoma multiforme. J Neurosurg 77:295–301

    Article  Google Scholar 

  14. Lang FF, Miller DC, Koslow M, et al (1994) Pathways leading to glioblastoma multiforme: a molecular analysis of genetic alterations in 65 astrocytic tumors. J Neurosurg 81:427–436

    PubMed  CAS  Google Scholar 

  15. Louis DN, Gusella JF (1995) A tiger behind many doors: multiple genetic pathways to malignant glioma. Trends Genet 11:412–415

    Article  PubMed  CAS  Google Scholar 

  16. Tchirkov A, Rolhion C, Bertrand S, et al (2001) IL-6 gene amplification and expression in human glioblastomas. Br J Cancer 85:518–522

    Article  PubMed  CAS  Google Scholar 

  17. Reifenberger G, Liu L, Ichimura K, et al (1993) Amplification and overexpression of the MDM2 gene in a subset of human malignant gliomas without p53 mutations. Cancer Res 53:2736–2739

    PubMed  CAS  Google Scholar 

  18. Reifenberger G, Ichimura K, Reifenberger J, et al (1996) Refined mapping of 12q13-q15 amplicons in human malignant gliomas suggests CDK4/SAS and MDM2 as independent amplification targets. Cancer Res 56:5141–5145

    PubMed  CAS  Google Scholar 

  19. Bertin R, Acquaviva C, Mirebeau D, et al (2003) CDKN2A, CDKN2B, and MTAP gene dosage permits precise characterization of mono- and bi-allelic 9q21 deletions in childhood acute lymphoblastic leukemia. Genes Chromosomes Cancer 37:44–57

    Article  PubMed  CAS  Google Scholar 

  20. Hermanson M, Funa K, Hartman M et al (1992) Platelet-derived growth factor and its receptors in human glioma tissue: expression of messenger RNA and protein suggests the presence of autocrine and paracrine loops. Cancer Res 52:3213–3219

    PubMed  CAS  Google Scholar 

  21. Smits A, Funa K (1998) Platelet-derived growth factor (PDGF) in primary brain tumours of neuroglial origin. Histol Histopathol 13:511–520

    PubMed  CAS  Google Scholar 

  22. Smithey BE, Pappo AS, Hill DA (2002) C-kit expression in pediatric solid tumors: a comparative immunohistochemical study. Am J Surg Pathol 26:486–492

    Article  PubMed  Google Scholar 

  23. Collins VP (1995) Gene amplification in human gliomas. Glia 15:289–296

    Article  PubMed  CAS  Google Scholar 

  24. Hui AB, Lo KW, Yin XL, et al (2001) Detection of multiple gene amplifications in glioblastoma multiforme using array-based comparative genomic hybridization. Lab Invest 81:717–723

    Article  PubMed  CAS  Google Scholar 

  25. Mollenhauer J, Holmskov U, Wiemann S, et al (1999) The genomic structure of the DMBT1 gene: evidence for a region with susceptibility to genomic instability. Oncogene 18:6233–6240

    Article  PubMed  CAS  Google Scholar 

  26. Bostrom J, Cobbers JM, Wolter M, et al (1998) Mutation of the PTEN (MMAC1) tumor suppressor gene in a subset of glioblastomas but not in meningiomas with loss of chromosome arm 10q. Cancer Res 58:29–33

    PubMed  CAS  Google Scholar 

  27. Rasheed BK, Stenzel TT, McLendon RE, et al (1997) PTEN gene mutations are seen in high-grade but not in low-grade gliomas. Cancer Res 57:4187–4190

    PubMed  CAS  Google Scholar 

  28. Shingu T, Yamada K, Hara N, et al (2003) Growth inhibition of human malignant glioma cells induced by the PI3-K-specific inhibitor. J Neurosurg 98:154–161

    Article  PubMed  CAS  Google Scholar 

  29. Christopher SA, Diegelman P, Porter CW, et al (2002) Methylthioadenosine phosphorylase, a gene frequently codeleted with p16(cdkN2a/ARF), acts as a tumor suppressor in a breast cancer cell line. Cancer Res 62:6639–6644

    PubMed  CAS  Google Scholar 

  30. Biernat W, Tohma Y, Yonekawa Y et al (1997) Alterations of cell cycle regulatory genes in primary (de novo) and secondary glioblastomas. Acta Neuropathol 94:303–309

    Article  PubMed  CAS  Google Scholar 

  31. Yano S, Kanematsu T, Miki T, et al (2003) A report of two bronchioloalveolar carcinoma cases which were rapidly improved by treatment with the epidermal growth factor receptor tyrosine kinase inhibitor ZD1839 (“Iressa”). Cancer Sci 94:453–458

    Article  PubMed  CAS  Google Scholar 

  32. Vitali R, Cesi V, Nicotra MR, et al (2003) c-Kit is preferentially expressed in MYCN-amplified neuroblastoma and its effect on cell proliferation is inhibited in vitro by STI-571. Int J Cancer 106:147–152

    Article  PubMed  CAS  Google Scholar 

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Correspondence to Motohiko Maruno.

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Suzuki, T., Maruno, M., Wada, K. et al. Genetic analysis of human glioblastomas using a genomic microarray system. Brain Tumor Pathol 21, 27–34 (2004). https://doi.org/10.1007/BF02482174

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  • DOI: https://doi.org/10.1007/BF02482174

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