Top

Published in:

01-01-2006 | Regular Paper

Identification of histological markers for malignant glioma by genome-wide expression analysis: dynein, α-PIX and sorcin

Authors: Takashi Yokota, Jun Kouno, Koji Adachi, Hiroshi Takahashi, Akira Teramoto, Koshi Matsumoto, Yuichi Sugisaki, Masamitsu Onda, Tatsuhiko Tsunoda

Published in: Acta Neuropathologica | Issue 1/2006

Abstract

Glioblastoma multiforme (GBM), the most malignant class of glial neoplasm (grade IV in WHO criteria), carries the worst clinical prognosis among primary brain tumors in adults. To identify a set of genes involved in the tumorigenesis of GBM, we evaluated expression profiles of GBM tissues from 11 patients using a cDNA microarray representing 25,344 human genes. By comparing the profiles with those of normal brain tissue, we identified a number of differentially expressed genes: 54 with increased expression and 45 with reduced expression in GBMs. Semi-quantitative RT-PCR experiments with 6 of those genes confirmed higher expression of DNCH2, ARHGEF6, NPM1 and SRI and lower expression of NRGN and TM4SF2 in GBM tumors. Immunohistochemical staining for 3 of the respective gene products, dynein (product of DNCH2), α-PIX (product of ARHGEF6), and sorcin (product of SRI) indicated that this technique might be useful for histological grading of glial tumors. To establish criteria for this diagnostic approach, we scored glial tumor tissues of different histological grades according to the staining results; the scores were significantly higher in anaplastic astrocytomas and GBMs than in diffuse astrocytomas or normal brain tissues. These findings indicated that levels of these three proteins might serve as histological markers for malignant glioma classification.

Baudier J, Deloulme JC, Van Dorsselaer A, Black D, Matthes HW (1991) Purification and characterization of a brain-specific protein kinase C substrate, neurogranin (p17): identification of a consensus amino acid sequence between neurogranin and neuromodulin (GAP43) that corresponds to the protein kinase C phosphorylation site and the calmodulin-binding domain. J Biol Chem 266:229–237PubMed

Bresalier RS, Ho SB, Schoeppner HL, Kim YS, Sleisenger MH, Brodt P, Byrd JC (1996) Enhanced sialylation of mucin-associated carbohydrate structures in human colon cancer metastasis. Gastroenterology 110:1354–1367CrossRefPubMed

Bresalier RS, Yan PS, Byrd JC, Lotan R, Raz A (1997) Expression of the endogenous galactose-binding protein galectin-3 correlates with the malignant potential of tumors in the central nervous system. Cancer 80:776–787CrossRefPubMed

Cavenee WK, Furnari FB, Nagane M, Huang HJS, Newcomb EW, Bigner DD, Weller M, Berens ME, Plate KH, Israel MA, Npbel MD, Kleihues P (2000) Diffusely infiltrating astrocytomas. In: Kleihues P, Cavenee WK (eds) Tumors of the Nervous System. IARC Press, Lyon, pp 10–21

Chan WY, Liu QR, Borjigin J, Busch H, Rennert OM, Tease LA, Chan PK (1989) Characterization of the cDNA encoding human nucleophosmin and studies of its role in normal and abnormal growth. Biochemistry 28:1033–1039CrossRefPubMed

Chavis P, Westbrook G (2001) Integrins mediate functional pre- and postsynaptic maturation at a hippocampal synapse. Nature 411:317–321CrossRefPubMed

Devireddy LR, Green MR (2003) Transcriptional program of apoptosis induction following interleukin 2 deprivation: identification of RC3, a calcium/calmodulin binding protein, as a novel proapoptotic factor. Mol Cell Biol 23:4532–4541CrossRefPubMed

Fuller GN, Hess KR, Rhee CH, Yung WK, Sawaya RA, Bruner JM, Zhang W (2002) Molecular classification of human diffuse gliomas by multidimensional scaling analysis of gene expression profiles parallels morphology-based classification, correlates with survival, and reveals clinically relevant novel glioma subsets. Brain Pathol 12:108–116PubMed

Giannakakou P, Sackett DL, Ward Y, Webster KR, Blagosklonny MV, Fojo T (2000) p53 is associated with cellular microtubules and is transported to the nucleus by dynein. Nat Cell Biol 2:709–717CrossRefPubMed

10.

Hoelzinger DB, Mariani L, Weis J, Woyke T, Berens TJ, McDonough WS, Sloan A, Coons SW, Berens ME (2005) Gene expression profile of glioblastoma multiforme invasive phenotype points to new therapeutic targets. Neoplasia 7:7–16PubMed

11.

Hunter S, Young A, Olson J, Brat DJ, Bowers G, Wilcox JN, Jaye D, Mendrinos S, Neish A (2002) Differential expression between pilocytic and anaplastic astrocytomas: identification of apolipoprotein D as a marker for low-grade, non-infiltrating primary CNS neoplasms. J Neuropathol Exp Neurol 61:275–281PubMed

12.

Kim S, Dougherty ER, Shmulevich I, Hess KR, Hamilton SR, Trent JM, Fuller GN, Zhang W (2002) Identification of combination gene sets for glioma classification. Mol Cancer Ther 1:1229–1236PubMed

13.

Kleihues P, Louis DN, Scheithauer BW, Rorke LB, Reifenberger G, Burger PC, Cavenee WK (2002) The WHO classification of tumors of the nervous system. J Neuropathol Exp Neurol 61:215–225PubMed

14.

Kutsche K, Yntema H, Brandt A, Jantke I, Nothwang HG, Orth U, Boavida MG, David D, Chelly J, Fryns JP, Moraine C, Ropers HH, Hamel BC, Bokhoven H van, Gal A (2000) Mutations in ARHGEF6, encoding a guanine nucleotide exchange factor for Rho GTPases, in patients with X-linked mental retardation. Nat Genet 26:247–250CrossRefPubMed

15.

Ligon KL, Alberta JA, Kho AT, Weiss J, Kwaan MR, Nutt CL, Louis DN, Stiles CD, Rowitch DH (2004) The oligodendroglial lineage marker OLIG2 is universally expressed in diffuse gliomas. J Neuropathol Exp Neurol 63:499–509PubMed

16.

Loging WT, Lal A, Siu IM, Loney TL, Wikstrand CJ, Marra MA, Prange C, Bigner DD, Strausberg RL, Riggins GJ (2000) Identifying potential tumor markers and antigens by database mining and rapid expression screening. Genome Res 10:1393–1402CrossRefPubMed

17.

Manos EJ, Jones DA (2001) Assessment of tumor necrosis factor receptor and Fas signaling pathway by transcriptional profiling. Cancer Res 61:433–438PubMed

18.

Manser E, Loo TH, Koh CG, Zhao ZS, Chen XQ, Tan L, Tan I, Leung T, Lim L (1998) PAK kinases are directly coupled to the PIX family of nucleotide exchange factors. Mol Cell 1:183–192CrossRefPubMed

19.

Markert JM, Fuller CM, Gillespie GY, Bubien JK, McLean LA, Hong RL, Lee K, Gullans SR, Mapstone TB, Benos DJ (2001) Differential gene expression profiling in human brain tumors. Physiol Genomics 5:21–33PubMed

20.

Milner B, Squire LR, Kandel ER (1998) Cognitive neuroscience and the study of memory. Neuron 20:445–468CrossRefPubMed

21.

Mischel PS, Shai R, Shi T, Horvath S, Lu KV, Choe G, Seligson D, Kremen TJ, Palotie A, Liau LM, Cloughesy TF, Nelson SF (2003) Identification of molecular subtypes of glioblastoma by gene expression profiling. Oncogene 22:2361–2373CrossRefPubMed

22.

Nagahata T, Onda M, Emi M, Nagai H, Tsumagari K, Fujimoto T, Hirano A, Sato T, Nishikawa K, Akiyama H, Sakamoto G, Kasumi F, Miki Y, Tanaka T, Tsunoda T (2004) Expression profiling to predict postoperative prognosis for estrogen receptor-negative breast cancers by analysis of 25,344 genes on a cDNA microarray. Cancer Sci 95:218–225CrossRefPubMed

23.

Nutt CL, Mani DR, Betensky RA, Tamayo P, Cairncross JG, Ladd C, Pohl U, Hartmann C, McLaughlin ME, Batchelor TT, Black PM, Deimling A von, Pomeroy SL, Golub TR, Louis DN (2003) Gene expression-based classification of malignant gliomas correlates better with survival than histological classification. Cancer Res 63:1602–1607PubMed

24.

Okuda M (2002) The role of nucleophosmin in centrosome duplication. Oncogene 21:6170–6174CrossRefPubMed

25.

Okuda M, Horn HF, Tarapore P, Tokuyama Y, Smulian AG, Chan PK, Knudsen ES, Hofmann IA, Snyder JD, Bove KE, Fukasawa K (2000) Nucleophosmin/B23 is a target of CDK2/cyclin E in centrosome duplication. Cell 103:127–140CrossRefPubMed

26.

Parekh HK, Deng HB, Choudhary K, Houser SR, Simpkins H (2002) Overexpression of sorcin, a calcium-binding protein, induces a low level of paclitaxel resistance in human ovarian and breast cancer cells. Biochem Pharmacol 63:1149–1158CrossRefPubMed

27.

Rataboul P, Faucon Biguet N, Vernier P, De Vitry F, Boularand S, Privat A, Mallet J (1988) Identification of a human glial fibrillary acidic protein cDNA: a tool for the molecular analysis of reactive gliosis in the mammalian central nervous system. J Neurosci Res 20:165–175CrossRefPubMed

28.

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 61:6885–6891PubMed

29.

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 60:6617–6622PubMed

30.

Rozen S, Skaletsky HJ (2000) Primer 3 on the WWW for general users and for biologist programmers. In: Krawetz S, Misener S (eds) Bioinformatics methods and protocols: Methods in molecular biology. Humana Press, Totowa, pp 365–386

31.

Tan Y, Li G, Zhao C, Wang J, Zhao H, Xue Y, Han M, Yang C (2003) Expression of sorcin predicts poor outcome in acute myeloid leukemia. Leuk Res 27:125–131CrossRefPubMed

32.

Tanwar MK, Gilbert MR, Holland EC (2002) Gene expression microarray analysis reveals YKL-40 to be a potential serum marker for malignant character in human glioma. Cancer Res 62:4364–4368PubMed

33.

Vaisberg EA, Grissom PM, McIntosh JR (1996) Mammalian cells express three distinct dynein heavy chains that are localized to different cytoplasmic organelles. J Cell Biol 133:831–842CrossRefPubMed

34.

Wang SL, Tam MF, Ho YS, Pai SH, Kao MC (1995) Isolation and molecular cloning of human sorcin a calcium-binding protein in vincristine-resistant HOB1 lymphoma cells. Biochim Biophys Acta 1260:285–293PubMed

35.

Yang YH, Dudoit S, Luu P, Lin DM, Peng V, Ngai J, Speed TP (2002) Normalization for cDNA microarray data: a robust composite method addressing single and multiple slide systematic variation. Nucleic Acids Res 30:e15CrossRefPubMed

36.

Young AN, Oliveira Salles PG de, Lim SD, Cohen C, Petros JA, Marshall FF, Neish AS, Amin MB (2003) Beta defensin-1, parvalbumin, and vimentin: a panel of diagnostic immunohistochemical markers for renal tumors derived from gene expression profiling studies using cDNA microarrays. Am J Surg Pathol 27:199–205CrossRefPubMed

37.

Yoshii S, Tanaka Y, Ttsuki Y, Wang DY, Guo RJ, Zhu Y, Ullevitch RJ, Takeda R, Hanai H, Kaneko E, Sugimura H (1999) AlphaPIX nucleotide exchange factor is activated by interaction with phosphatidylinositol 3-kinase. Oncogene 18:5680–5690CrossRefPubMed

38.

Zemni R, Bienvenu T, Vinet MC, Sefiani A, Carrie A, Billuart P, McDonell N, Couvert P, Francis F, Chafey P, Fauchereau F, Friocourt G, Portes V des, Cardona A, Frints S, Meindl A, Brandau O, Ronce N, Moraine C, Bokhoven H van, Ropers HH, Sudbrak R, Kahn A, Fryns JP, Beldjord C, Chelly J (2000) A new gene involved in X-linked mental retardation identified by analysis of an X; 2 balanced translocation. Nat Genet 24:167–170CrossRefPubMed

Title: Identification of histological markers for malignant glioma by genome-wide expression analysis: dynein, α-PIX and sorcin
Authors: Takashi Yokota
Jun Kouno
Koji Adachi
Hiroshi Takahashi
Akira Teramoto
Koshi Matsumoto
Yuichi Sugisaki
Masamitsu Onda
Tatsuhiko Tsunoda
Publication date: 01-01-2006
Publisher: Springer-Verlag
Published in: Acta Neuropathologica / Issue 1/2006
Print ISSN: 0001-6322
Electronic ISSN: 1432-0533
DOI: https://doi.org/10.1007/s00401-005-1085-6

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Identification of histological markers for malignant glioma by genome-wide expression analysis: dynein, α-PIX and sorcin

Abstract

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Abstract

Please log in to get access to this content

Other articles of this Issue 1/2006

Transition of areas of eosinophilic neurons and reactive astrocytes to delayed cortical infarcts after transient unilateral forebrain ischemia in Mongolian gerbils

Comments on the WHO 2004 classification of pituitary tumors

The new WHO classification of pituitary tumors: highlights and areas of controversy

A 3’-UTR polymorphism in the oxidized LDL receptor 1 gene increases Aβ40 load as cerebral amyloid angiopathy in Alzheimer’s disease

Comments on the WHO histological classification of pituitary tumors

Acknowledgement to Referees 2005