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BMC Cancer

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Open Access 01-12-2004 | Research article

Identification of astrocytoma associated genes including cell surface markers

Authors: Kathy Boon, Jennifer B Edwards, Charles G Eberhart, Gregory J Riggins

Published in: BMC Cancer | Issue 1/2004

Abstract

Background

Despite intense effort the treatment options for the invasive astrocytic tumors are still limited to surgery and radiation therapy, with chemotherapy showing little or no increase in survival. The generation of Serial Analysis of Gene Expression (SAGE) profiles is expected to aid in the identification of astrocytoma-associated genes and highly expressed cell surface genes as molecular therapeutic targets. SAGE tag counts can be easily added to public expression databases and quickly disseminated to research efforts worldwide.

Methods

We generated and analyzed the SAGE transcription profiles of 25 primary grade II, III and IV astrocytomas [1]. These profiles were produced as part of the Cancer Genome Anatomy Project's SAGE Genie [2], and were used in an in silico search for candidate therapeutic targets by comparing astrocytoma to normal brain transcription. Real-time PCR and immunohistochemistry were used for the validation of selected candidate target genes in 2 independent sets of primary tumors.

Results

A restricted set of tumor-associated genes was identified for each grade that included genes not previously associated with astrocytomas (e.g. VCAM1, SMOC1, and thymidylate synthetase), with a high percentage of cell surface genes. Two genes with available antibodies, Aquaporin 1 and Topoisomerase 2A, showed protein expression consistent with transcript level predictions.

Conclusions

This survey of transcription in malignant and normal brain tissues reveals a small subset of human genes that are activated in malignant astrocytomas. In addition to providing insights into pathway biology, we have revealed and quantified expression for a significant portion of cell surface and extra-cellular astrocytoma genes.

Available only for authorised users

Boon Kathy, Edwards Jennifer B, Siu I-Mei, Olschner Deric, Eberhart Charles G, Marra Marco A, Strausberg Robert L, Riggins Gregory J.: Comparison of medulloblastoma and normal neural transcriptomes identifies a restricted set of activated genes. Oncogene. 2003, 22: 7687 -77694. 10.1038/sj.onc.1207043.CrossRefPubMed

Boon Kathy, Osorio Elisson C., Greenhut Susan F., Schaefer Carl F., Shoemaker Jennifer, Polyak Kornelia, Morin Patrice J., Buetow Kenneth H., Strausberg Robert L., de Souza Sandro J., Riggins Gregory J.: An anatomy of normal and malignant gene expression. PNAS. 2002, 99: 11287-11292. 10.1073/pnas.152324199.CrossRefPubMedPubMedCentral

Shai R Shi T, Kremen TJ, Horvath S, Liau LM, Cloughesy TF, Mischel PS, Nelson SF.: Gene expression profiling identifies molecular subtypes of gliomas. Oncogene. 2003, 22: 4918 -44923. 10.1038/sj.onc.1206753.CrossRefPubMed

Godard S, Getz G, Delorenzi M, Farmer P, Kobayashi H, Desbaillets I, Nozaki M, Diserens AC, Hamou MF, Dietrich PY, Regli L, Janzer RC, Bucher P, Stupp R, de Tribolet N, Domany E, Hegi ME: Classification of human astrocytic gliomas on the basis of gene expression: a correlated group of genes with angiogenic activity emerges as a strong predictor of subtypes. Cancer Res. 2003, 63: 6613-6625.PubMed

Fathallah-Shaykh HM, Rigen M, Zhao LJ, Bansal K, He B, Engelhard HH, Cerullo L, Roenn KV, Byrne R, Munoz L, Rosseau GL, Glick R, Lichtor T, DiSavino E: Mathematical modeling of noise and discovery of genetic expression classes in gliomas. Oncogene. 2002, 21: 7164-7174. 10.1038/sj.onc.1205654.CrossRefPubMed

Rickman DS, Bobek MP, Misek DE, Kuick R, Blaivas M, Kurnit DM, Taylor J, Hanash SM: Distinctive molecular profiles of high-grade and low-grade gliomas based on oligonucleotide microarray analysis. Cancer Res. 2001, 61: 6885-6891.PubMed

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

Lal A, Lash AE, Altschul SF, Velculescu V, Zhang L, McLendon RE, Marra MA, Prange C, Morin PJ, Polyak K, Papadopoulos N, Vogelstein B, Kinzler KW, Strausberg RL, Riggins GJ: A public database for gene expression in human cancers. Cancer Res. 1999, 59: 5403-5407.PubMed

Loging W. Troy, Lal Anita, Siu I-Mei, Loney Tania L., Wikstrand Carol J., Marra Marco A., Prange Christa, Bigner Darell D., Strausberg Robert L., Riggins Gregory J.: Identifying Potential Tumor Markers and Antigens by Database Mining and Rapid Expression Screening. Genome Res. 2000, 10: 1393-1402. 10.1101/gr.138000.CrossRefPubMedPubMedCentral

10.

Ljubimova JY, Khazenzon NM, Chen Z, Neyman YI, Turner L, Riedinger MS, Black KL: Gene expression abnormalities in human glial tumors identified by gene array. Int J Oncol. 2001, 18: 287-295.PubMed

11.

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

12.

Velculescu Victor E., Zhang Lin, Vogelstein Bert, Kinzler Kenneth W.: Serial Analysis of Gene Expression. Science. 1995, 270: 484-487.CrossRefPubMed

13.

Siu IM Lal A and Riggins GJ,: A database for regional gene expression in the human brain. Gene Expression Patterns. 2001, 1: 33-38. 10.1016/S1567-133X(01)00006-0.CrossRefPubMed

14.

Saha Saurabh, Bardelli Alberto, Buckhaults Phillip, Velculescu Victor E., Rago Carlo, Croix Brad St., Romans Katharine E., Choti Michael A., Lengauer Christoph, Kinzler Kenneth W., Vogelstein Bert: A Phosphatase Associated with Metastasis of Colorectal Cancer. Science. 2001, 294: 1343-1346. 10.1126/science.1065817.CrossRefPubMed

15.

Kononen J Bubendorf L, Kallioniemi A, Barlund M, Schraml P, Leighton S, Torhorst J, Mihatsch MJ, Sauter G, Kallioniemi OP.: Tissue microarrays for high-throughput molecular profiling of tumor specimens. Nature Medicine. 1998, 4: 844 -8847.CrossRefPubMed

16.

Carver LA Schnitzer JE: Caveolae: minin little caves fro new cancer targets. Nature Reviews Cancer. 2003, 3: 571-581. 10.1038/nrc1146.CrossRefPubMed

17.

Sekine T, Masuko-Hongo K, Matsui T, Asahara H, Takigawa M, Nishioka K, Kato T: Recognition of YKL-39, a human cartilage related protein, as a target antigen in patients with rheumatoid arthritis. Ann Rheum Dis. 2001, 60: 49-54. 10.1136/ard.60.1.49.CrossRefPubMedPubMedCentral

18.

Heasley LE: Autocrine and paracrine signaling through neuropeptide receptors in human cancer. Oncogene. 2001, 20: 1563 -11569. 10.1038/sj.onc.1204183.CrossRefPubMed

19.

Vannahme Christian, Smyth Neil, Miosge Nicolai, Gosling Silke, Frie Christian, Paulsson Mats, Maurer Patrik, Hartmann Ursula: Characterization of SMOC-1, a Novel Modular Calcium-binding Protein in Basement Membranes. J Biol Chem. 2002, 277: 37977-37986. 10.1074/jbc.M203830200.CrossRefPubMed

20.

Munroe PB Olgunturk RO, Fryns JP, Van Maldergem L, Ziereisen F, Yuksel B, Gardiner RM, Chung E.: Mutations in the gene encoding the human matrix Gla protein cause Keutel syndrome. Nature Genetics. 1999, 21: 142 -1144. 10.1038/5102.CrossRefPubMed

21.

Mobasheri A Marples D.: Expression of the aquaporin 1 (AQP1) water channel in normal human tissues: a semi-quantitative study using tissue microarray technology. American Journal of Physiology. 2003

22.

Saadoun S, Papadopoulos MC, Davies DC, Krishna S, Bell BA: Aquaporin-4 expression is increased in oedematous human brain tumours. J Neurol Neurosurg Psychiatry. 2002, 72: 262-265. 10.1136/jnnp.72.2.262.CrossRefPubMedPubMedCentral

23.

Holden JA Townsend JJ.: DNA topoisomerase II-alpha as a proliferation marker in astrocytic neoplasms of the central nervous system: correlation with MIB1 expression and patient survival. Mod Pathol. 1999, 12: 1094 -11100.PubMed

24.

Vassal G Merlin JL, Terrier-Lacombe MJ, Grill J, Parker F, Sainte-Rose C, Aubert G, Morizet J, Sevenet N, Poullain MG, Lucas C, Kalifa C.: In vivo antitumor activity of S16020, a topoisomerase II inhibitor, and doxorubicin against human brain tumor xenografts. Cancer Chemother Pharmacol. 2003, 51: 385 -3394.PubMed

The pre-publication history for this paper can be accessed here:http://www.biomedcentral.com/1471-2407/4/39/prepub

Title: Identification of astrocytoma associated genes including cell surface markers
Authors: Kathy Boon
Jennifer B Edwards
Charles G Eberhart
Gregory J Riggins
Publication date: 01-12-2004
Publisher: BioMed Central
Published in: BMC Cancer / Issue 1/2004
Electronic ISSN: 1471-2407
DOI: https://doi.org/10.1186/1471-2407-4-39

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