(12) INTERNATIONAL APPLICATION PUBLISHED UNDER THE PATENT COOPERATION TREATY (PCT)

(19) World Intellectual Property Organization International Bureau

(43) International Publication Date PCT (10) International Publication Number 26 March 2009 (26.03.2009) WO 2009/039390 A2

(51) International Patent Classification: (74) Agents: MAYFIELD, Denise et al; Bell, Boyd & Lloyd C12Q 1/68 (2006.01) LLP, P.O. Box 1135, Chicago, Illinois 60690-1 135 (US). (81) Designated States (unless otherwise indicated, for every (21) International Application Number: kind of national protection available): AE, AG, AL, AM, PCT/US2008/077045 AO, AT,AU, AZ, BA, BB, BG, BH, BR, BW, BY, BZ, CA, CH, CN, CO, CR, CU, CZ, DE, DK, DM, DO, DZ, EC, EE, (22) International Filing Date: EG, ES, FI, GB, GD, GE, GH, GM, GT, HN, HR, HU, ID, 19 September 2008 (19.09.2008) IL, IN, IS, JP, KE, KG, KM, KN, KP, KR, KZ, LA, LC, LK, LR, LS, LT, LU, LY, MA, MD, ME, MG, MK, MN, MW, (25) Filing Language: English MX, MY, MZ, NA, NG, NI, NO, NZ, OM, PG, PH, PL, PT, RO, RS, RU, SC, SD, SE, SG, SK, SL, SM, ST, SV, SY,TJ, (26) Publication Language: English TM, TN, TR, TT, TZ, UA, UG, US, UZ, VC, VN, ZA, ZM, ZW (30) Priority Data: 60/974,010 20 September 2007 (20.09.2007) US (84) Designated States (unless otherwise indicated, for every kind of regional protection available): ARIPO (BW, GH, GM, KE, LS, MW, MZ, NA, SD, SL, SZ, TZ, UG, ZM, (71) Applicant (for all designated States except US): NAUREX ZW), Eurasian (AM, AZ, BY, KG, KZ, MD, RU, TJ, TM), INC. [US/US]; 1801 Maple Avenue, Suite 4300, Evanston, European (AT,BE, BG, CH, CY, CZ, DE, DK, EE, ES, FI, Illinois 60201 (US). FR, GB, GR, HR, HU, IE, IS, IT, LT,LU, LV,MC, MT, NL, NO, PL, PT, RO, SE, SI, SK, TR), OAPI (BF, BJ, CF, CG, (72) Inventors; and CI, CM, GA, GN, GQ, GW, ML, MR, NE, SN, TD, TG). (75) Inventors/Applicants (for US only): MOSKAL, Joseph, R. [US/US]; 801 Central Street, Evanston, Illinois 60201 Published: (US). KROES, Roger, A. [US/US]; 25174 North Virginia, — without international search report and to be republished Lake Zurich, Illinois 60047 (US). upon receipt of that report

(54) Title: THE DEVELOPMENT OF GLYCOBIOLOGY-B ASED THERAPEUTICS FOR THE TREATMENT OF BRAIN TU MORS

(57) Abstract: A unique panel of differentially expressed glioma-associated is identified, as well as a unique and differen tially expressed panel of non-glioma associated genes. Disclosed are methods for selecting -targeted therapeutic agents for the treatment and inhibition of glioblastoma, as well as anti-glioblastoma therapeutics themselves. Molecular constructs, such as aden oviral vectors, that include selected of the identified differentially expressed glioma associated genes and/or non-glioma associated genes are also provided. A focused oligonucleotide microarray of highly glioma specific oligonucleotide sequences is also provided. Microchips and/or other solid and semi-solid support matrices that include the oligonucleotides attached thereto are also provided. Methods for diagnosing glioblastoma in a patient are also provided employing a genetic microarray comprising the oligonucleotide sequences. TITLE OF THE INVENTION THE DEVELOPMENT OF GLYCOBIOLOGY-BASED THERAPEUTICS FOR THE TREATMENT OF BRAIN TUMORS

BACKGROUND [0001] Brain tumors are presently the leading cause of cancer death in children under the age of 20, only recently surpassing acute lymphoblastic leukemia (ALL). In addition, they are the third leading cause of cancer death in young adults ages 20-39 [4, 5]. Although not the most common form of cancer, brain tumors are clearly among the most devastating. Brain tumors are phenotypically and genotypically diverse, with over 120 different types of brain tumors currently classified [7]. As with most tumors, the classification of primary brain tumors is based on the precise tumor site, the anatomical structures involved, as well as tumorigenic tendencies. [0002] The etiology of primary brain tumors is virtually unknown. As such, neuro- oncology is an aggressive field of study, diligently striving to keep pace with advances in the field of cancer genetics. Current understanding of brain tumorigenesis, as well as their biological and clinical behavior, is rapidly expanding. However, significantly prolonged survival has only been experienced by a minority of patients diagnosed with certain subsets of tumors. [0003] Perhaps the most devastating of brain tumors are high grade gliomas, or glioblastoma multiforme (GBM). Glioblastomas represent 23% of all primary brain tumors, rapidly approaching the incidence of meningiomas, which are the most common primary brain tumor and represent 26% of all primary brain tumors [I]. Glioblastoma multiforme is nearly uniformly fatal, with median survival between 9 and 12 months from initial diagnosis. GBMs are highly invasive tumors, making complete surgical resection unachievable. Current multimodality therapy for GBMs including surgery, radiation therapy (RT), and chemotherapy is still the cornerstone of treatment but is largely ineffective, as the majority of patients experience progression or recurrence. [0004] Research on the glycobiology of brain tumors has been quite active with studies falling into three categories: descriptive studies identifying brain tumor-associated glycoconjugates, studies examining the expression of specific glycogene activities in brain tumors, and studies aimed at showing a functional relationship between specific glycoconjugates relevant to therapeutic development. [0005] The glycogene biosynthetic machinery, the , glycosyl hydrolases, and the genes that regulate their expression, is significantly altered in all forms of oncogenic transformation [34-37]. Surprisingly, however, there have been very few such studies with brain tumors. The cloning and sequencing of many of the human glycogenes has been accomplished. However, functional studies showing a direct link between altered glycoconjugate expression and cellular processes have not yet been reported. [0006] There have been reports in which some aspect of glycoconjugate biochemistry (e.g., inhibitors of biosynthesis, addition of cell-surface glycosphingolipids, addition of oligosaccharides or glycopeptides, etc.) has been manipulated leading to an inhibition of tumor growth, metastasis, etc. [46]. Swainsonine is one therapeutic candidate that has progressed into clinical trials. Swainsonine is an inhibitor of the Golgi-associated α- mannosidase II, and is implicated in the inhibition of or alterations in normal N-glycan biosynthesis on some glycoproteins [47]. Another therapeutic candidate is a GD2-based immunotherapy that targets gliomas [48]. While reportedly showing no toxic side effects, the GD2-based immunotherapy was unable to stimulate antibody formation or effect any tumor regression. Fujimoto et al. [49] has also reported that GM3 ganglioside, too, has therapeutic potential for patients with gliomas. [0007] Ishikawa and coworkers [50] screened phage-display random peptide libraries for peptides that bound to an anti-GDI α monoclonal antibody. A peptide was identified having adhesion-inhibition properties that also was effective at inhibiting metastasis when injected in vivo. Hanessian et al. [51] have created functionalized aryl β-D-glycopyranosides called "glycomers" that they report induce apoptosis in human glioma cell lines. Neurostatin, o-acetylated GDIb, has also been reported to inhibit the in vitro and in vivo proliferation of human glioma cell lines [52, 53]. A review by Rebbaa et al. [54] discusses the modulation of growth factor receptors in brain tumors by complex carbohydrates. [0008] These and other observations in the art demonstrate that a need continues to exist for novel neuro-oncology therapeutics, and in particular novel targeted neuro-oncology therapeutic strategies that can harness a growing knowledge base in brain tumor molecular biology.

SUMMARY [0009] The present invention, in a general and overall sense, presents a broad spectrum of glycobiology focused therapeutic agents and molecular biology based materials that, among other applications, possess accurate and specific clinical diagnostic and therapeutic uses in the field of neuro-oncology. [0010] Focused Microarray Oligonucleotide Panel: In one aspect, the invention provides a focused microarray of synthesized 45-mer oligonucleotides. These oligonucleotides may also include a 5'-amino linker. In addition, the invention provides for a solid substrate, such as a glass microscope slide, nylon membrane, nitrocellulose support material, glass or silica support, or other appropriate solid or semisolid medium, to provide a microchip that includes placed thereon a microarray of the oligonucleotides described herein, or a subset of selected of these oligonucleotides. Robotic systems which pipette nano to picomolar amounts of gene products onto the support are commercially available or can be built using commercially available materials. In some embodiments, the oligonucleotides may be described as having been arranged using robotic placement as covalently linked oligonucleotides onto a solid or semisolid substrate of choice. In some embodiments, the oligonucleotides are to be provided as an array spotted in quadruplicate onto an aldehyde-coated glass microscope slide.

[001 1] In some embodiments, the focused microarray oligonucleotides panel comprises two (2) or more oligonucleotide sequences of Table 1. By way of example, and in some embodiments, the panel comprises 2 or more specific probes having a sequence of SEQ

ID No: 2, SEQ ID No: 6, SEQ ID No: 11, SEQ ID No: 20, SEQ ID No: 23, SEQ ID No: 27, SEQ ID No. 31, SEQ ID No: 39 or any combination of 2 or more of these. In other embodiments, the Focused Microarray Panel comprises forty-two (42) glioma and non- glioma gene specific probes. These are listed in Table 1: Table 1 Oligonucleotide Sequence used on Microarray SEQ ID

5' CAAATATTCTGGGGTTGAGGGAAATTGCTGCTGTCTACAAAATGC 3' (1) 5' GAGCCAAACATCCTACAAGACACAGTGACCATACTAATTATACCC 3' (2) 5' CCTGGCTTCTAGATCTGGAACCTTACCACGTTACTGCATACTGAT 3 (3) 5' CGTTATCATTGGTCTGGTGAGATGTTTCATATTTGTGACAGTTAA 3' (4) 5' CCAGATCAGTCAGAGCCCCTACAGCATTGTTAAGAAAGTATTTGA 3' (5) Oligonucleotide Sequence used on Microarray SEQ ID 5' TAGTGTATCATGTTTTCCCTGTTGGTATGTAGCCTGGATAAATGC 3' (6)

5' TCCCTGTATAGAAATGTGGAATTGTCCCTTTGTAGCCAACTATAA 3' (V) 5' CACTCCATATATTCAGCATCGTCAGAGAAACCCAAATCAGCCATT 3' (8) ' ATGCTAAGGAACACCACATGCCATTATTAACTTCACATTCTACAA 3' (9) ' CATCTACTTGGCAAGGTCATAGACAATTCCTCCAGAGACACTGAG 3' (10) ' TATGATCGGTTGGGCTTCCTCCTGAATCTGGACTCTAAACTCTCA 3' (H) 'AGACGCCTACAACAAGAAGCAGACCATTCACTACTATGAGCAGAT 3' (12)

' GGCTTCCCTGTAATCCTTTCTGCTCCTTGGTACTTAGATTTGATT 3' (13)

' GAGGCGGAAGTCTAGAGCTGCATGATCTGATAGGGTTTGTGACAG 3' (14) ' GGACCTCGTCTTTATGAAACACACACCTGGAATAAAACCACTTCT 3' (15) ' CAGCATAATGATTTGAGATTGGTCCATGTTGTGTGATTCAGTGGT 3' (16) ' CTTTGTGAGCCGTGTCGTATGACCTAGTAAACTTTGTACCAATTC 3' (17) ' AATCATCCAGTCATTCCAATGGCAAATAAGTTCTCACCTACCCTT 3' (18) ' AAGAAAGTGAAATGAGCCGACAGCCCAGGTGATAGAAATAAATTG3' (19) ' CCCCATACCCTCACCCTTAAAATTCTCCTGTAACTCAACTAACAA 3' (20) ' GGTTCACCCACCTGGAGCTGGAATTATCACTTCCGAAATAAAGCG 3' (21) ' CAGTTCTGAAGATTCACGTATCCATCTGGAGACCTACAGGAAGAA 3' (22) ' TAAAGAGTCAGACGCCACAGGCATTCCCATTAAAGTCAGAAACTA 3' (23) ' CTGGGCTGGGTATGTGCCTACCGATGACAATGTGTAAATAAATGC 3' (24) ' GGTTTTATCTTGGCTTTTAGTAATCATGTTGGCTGGTCTGGTCAC 3' (25) ' GTGACTGCCCCAGACTTGGTTTTGTAATGATTTGTACAGGAATAA 3' (26) ' CTCAGTCCAGAGACCTAACATTCAGAATATAGCATTGGTTGCCTA 3' (27) ' TTTGAACAACTGACTCTTGATGGACACAACCTTCCTTCTCTCGTC 3' (28) ' TATGTGTGGCATCCATGTTGGTTTCGTCTGTCTGTAATGTGAATT 3' (29) ' CCTCACGGCCGATGCTCTGCAGTCTGACAAGCTTCAGACCTGGAC 3' (30) ' TGGTAATTTATCCTTCCTAACTCTTTAATCCTGAATGATGGTTGG 3' (31) ' GAGGACCTGACCCTACTCCCTTGCCCTAGATAGTTTATTATTATT 3' (32) ' AATACCCACACTTACCTTAATACAAACATCCCAGCAACAGCACAT 3' (33) ' CTCAGTCCAGAGACCTAACATTCAGAATATAGCATTGGTTGCCTA 3' (34) ' CTGCCCTCCGCCATCCCTGCTATTTAAATTATTTAAGGTCTCTGG 3' (35) ' CTGAGGAGCAGCTGTTCTGATGCACGGGAACAAGCAGCACCTGCA 3' (36) ' CTTATGGGAGCTGGCACGTCACCCACAGCCTGGCAGCTCTGATCA 3' (37) ' AAAAGCTTATGGGAGCTGGCACGTCACAAAAAGAAAAAAACCAAG3' (38)

' CGTTATCATTGGTCTGGTGAGATGTTTCATATTTGTGACAGTTAA 3' (39)

'ACAATGGAATCTTCCCTCTGTTCTCTGATAACCTACTTGCTTACT 3' (40) 5' TCCTTGCAGCCTAGCAGTTTATAGTTCTGAGATGGAAAGTTGAAG 3 (41)

5' CTTTGACCCTAAGAATAAGCACTGTGTGTTTCAAGGTGACCTCCT 3 (42)

[0012] Methods of Screening for a Therapeutic Target Gene or Genes and Compounds: In yet another aspect, a method for screening a candidate library of compounds suitable for identifying a selected candidate compound for treating a glioma is provided. In some embodiments, the devised 45-mer oligonucleotides that were created with information disclosed in the present paper that compose the transcriptome signature comprising the genes encoding MAN2A2, ST6GALNAC5, ST6GAL1, OGT, B3GNT6, POFUTl, CHI3L1, ST3GAL3, alone or in any combination with each other as well as one or more of the other genes described here in the glioma associated gene panel or non-glioma associated gene panel, will be included as part of a screening panel to be used in selecting therapeutic agent(s). These panels may also be used to identify target genes for inhibiting cancer (glioma) in a particular patient. [0013] In some embodiments, a method is provided for identifying glycobiology based therapeutics for treating glioblastoma through use of preparations that modify the expression of a specific set of genes. In some embodiments, the screening method comprises exposing a candidate substance from a library of potential therapeutic compounds to a cell culture of human glioma brain cells, such as a culture of cells from cell line SNB 19, D54MG, U87MG, U373MG, U l 18MG, U251 or A172, and measuring expression levels of a selected target gene or genes from a human glioma-associated gene panel and optionally for expression levels of a selected target gene from a non-glioma associated gene panel. [0014] A candidate substance will be selected that is capable of reducing and/or inhibiting expression levels of 2 or more genes of the glioma-associated gene panel, increasing or reducing inhibition of expression of 2 or more selected target nonglioma associated genes of a non-glioma associated gene panel, or 1 selected target glioma associated gene and 1 selected target non-glioma associated gene. The level of expression of a selected target gene from a culture having been exposed to a candidate substance may be assessed using any 1, 2 or more of the 45-mer oligonucleotides provided in Table 1. As each of the 45-mer oligonucleotides specifically hybridizes to a uniquely identifiable transcript of a specific glioma-associated or non-glioma associated gene, determining which specific gene product is being inhibited and/or enhanced by a candidate substance may also be specifically identified using this method. Thus, the present methods provide for specifically identifiable glioma-associated gene targeted therapeutics and specifically targeted non-glioma associated gene targeted therapeutics. [0015] The glioblastoma-associated genes include those listed in Table 2. Table 2 Glioma Associated Gene Panel NM 000149 3 (galactoside 3(4)-L-Fucosyltransferase, Lewis blood group included) (FUT3) NM 001276 Chitinase 3-like 1 (cartilage glycoprotein-39, YKL-40) (CHI3L1) NM 002 103 1 (GYS 1) NM 003032 l (β-galactoside α2, 6-sialyltransferase) (SIATl), transcript variant 2 NM 005228 Epidermal growth factor receptor (EGFR) NM 015352 O-fucosyltransferase 1 (POFUTl), transcript variant 1 NM 03 1302 Glycogene 8 domain containing 2 (GLT8D2) NM 032528 β-galactoside α2, 6-sialyltransferase II (ST6GaIII) NM 033167 UDP-GaI :β-GlcNAc βl , 3-, polypeptide 3 (B3GALT3), transcript variant 2 NM 153286 Hyaluronoglucosaminidase 1 (HYALl), transcript variant 6 NM 174963 ST3 β-galactoside α2,3-sialyltransferase 3 (ST3GAL3), transcript variant 1 NM_006278 Sialyltransferase 4C (β-galactoside α2,3-sialyltransferase) (SIAT4C) NM 000521 Hexosaminidase B (β-polypeptide) (HEXB) NM 002409 Mannosyl (β1,4-)-glycoprotein β1,4-N-acetylglucosaminyltransferase (MGAT3) [0016] By way of example, the non-glioblastoma-associated gene panel includes genes listed in Table 3. Table 3 Non-Glioma Associated Gene Panel AB 032956 UDP-N-acetyl- α-d-galactosamine polypeptide N- acetylgalactosaminyltransferase-like 1 (GALNTLl) NM 000153 Galactosylceramidase (Krabbe disease) (GALC) NM 000188 Hexokinase 1 (HKl), transcript variant 1 NM 002372 α-mannosidase, class 2A, member 1 (MAN2A1) NM 003360 UDP glycogene 8 (UDP galactose ceramide galactosyltransferase) (UGT8) NM 003605 O-linked N-acetylglucosamine (GIcNAc) (UDP-N- acetylglucosamine : polypeptide-N-acetylglucosaminyltransferase) (OGT), transcript variant 3 NM 004455 Exostoses (multiple)-like 1 (EXTLl) NM 004737 Glycogene-like, LARGE (MDCID), transcript variant 1 NM 006122 α-mannosidase, class 2A, member 2 (MAN2A2) NM 006876 UDP-GIcNAc :β-Gal, βl ,3-N-acetylglucosaminyltransferase 6 (B3GNT6) NM 012215 Meningioma expressed antigen 5 (hyaluronidase) (MGEA5) NM 013443 ST6 (α-N-acetyl-neuraminyl-2,3 β galactosyl- l,3)-N-acetylgalactosaminide α2,6-sialyltransferase 6 (ST6GALNAC6) NM 018644 βl ,3-glucurony^transferase 1 ( P) (B3GAT1), transcript variant 1 NM 019109 β1,4 (HMT-1) NM 020742 Neuroligin 4 (NLGN4) transcript variant 1 NM 024344 Calpain 3 (p94) (CAPN3), transcript variant 2 NM 030965 ST6 (α-N-acetyl-neuraminyl-2,3- β-galactosyl- 1,3)-N- acetylgalactosaminide α2,6-sialyltransferase 5 (ST6GALNAC5) NM 033 158 Hyaluronoglucosaminidase 2 (HYAL2), transcript variant 2 NM 033309 UDP-GIcNAc :βGal βl,3-N-acetylglucosaminyltransferase 9 (B3GNT9) NM 054025 β1,3-glucurony^transferase 1 (glucuronosyltransferase P) (B3GAT1), transcript variant 2 NM 152312 Glycogene-like IB, LARGE2 (GYLTLlB) NM 173088 Calpain 3, (p94) (CAPN3), transcript variant 4 NM 173089 Calpain 3, (p94) (CAPN3), transcript variant 5 NM 173090 Calpain 3, (p94) (CAPN3), transcript variant 6 NM 173216 ST6 β-galactoside α2,6-sialyltransferase (ST6GAL1) NM 000147 α-L-fucosidase 1 (FUCAl) NM 002406 Mannosyl (αl,3-)-glycoprotein βl,2-N-acetylglucosaminyltransferase (MGATl) NM 002410 Mannosyl (αl,6-)-glycoprotein βl,6-N-acetylglucosaminyltransferase (MGAT5)

[0017] Method of Treatment: In another aspect, the present invention, among other things, provides a method for treating glioblastoma in a patient. In some embodiments, the method comprises treating a patient having or at risk of having a glioma whose tumor demonstrates an identifiable glioma gene expression profile comprising a decreased expression level of a MAN2A2 gene, a ST6GALNAC5 gene, a ST6GAL1 gene, a OGT gene, a B3GNT6 gene, or any combination of these, an increased (elevated) expression level of a POFUTl gene, a CHI3L1 gene, a ST3GAL3 gene, or any combination of these, with a viral vector having a sequence that comprises a therapeutic gene sequence appropriate for the patients identifiable glioma gene expression profile. For example, where the patient expression profile demonstrates a decreased expression level of a MAN2A2 gene, a ST6GALNAC5 gene, a ST6GAL1 gene, a OGT gene, a B3GNT6 gene, or any combination of these, relative to a non-glioma expression level of one or both of these genes, the adenoviral vector will comprise a gene sequence that corresponds to the coding region of the gene exhibiting decreased expression. Where the patient expression profile demonstrates an increased expression level of POFUTl gene, a CHI3L1 gene, a ST3GAL3 gene, or any combination of these, the adenoviral vector will comprise a gene sequence that corresponds to an antisense molecule specific for the gene that is increased (elevated) relative to a non-glioma expression level of one or more of these genes. [0018] Inhibiting expression of glioma-associated gene(s): In one embodiment of the present invention, a method for inhibiting a glioma brain tumor is provided comprising altering expression pattern levels of a glioma-associated gene or genes in a patient, such as a POFUTl gene, a CHI3L1 gene, a ST3GAL3 gene, or any combination of these, in a patient having being diagnosed as having glioma, particularly, a grade 4 glioma. These glioma- associated genes, among others, have been characterized in the present disclosure as being more highly expressed in the tumor of a patient having been diagnosed as having a glioma, compared to expression levels of the gene in normal, non-glioma brain tissue. Therefore, as part of the present method for inhibiting glioma, a treatment method would comprise inhibiting the level of expression of the POFUTl gene, a CHI3L1 gene, a ST3GAL3 gene,, alone or in conjunction with other of the glioma-associated gene panel described herein, in a patient having a glioma so as to achieve a relative level of the expression of these genes that is about the same as, or at least a reduced level of expression that is not more than about 20% to 30% higher, than the expression levels of these genes in a normal (non-glioma) human brain tissue. [0019] By way of example, the method may comprise administering a recombinant adenoviral vector particle having a sequence encoding an antisense molecule (e.g., antisense oligonucleotide, ribozyme, siRNA, or shRNA) specific for a selected glioma-associated target gene or genes, such as POFUTl gene, a CHBLl gene, a ST3GAL3 gene, or any combination of these, to a patient having been diagnosed to have a glioma, and inhibiting and/or reducing the elevated expression of the glioma-associated target gene or genes in the patient to a non-glioma associated gene expression level of the selected glioma-associated target gene or genes, such as POFUTl, CHBLl, or ST3GAL3. [0020] Increasing expression of non-glioma associated genes: In yet another embodiment, a method for inhibiting a glioma is provided comprising altering expression pattern levels of a non-glioma associated gene or genes in a patient, such as a MAN2A2 gene, a ST6GALNAC5 gene, a ST6GAL1 gene, a OGT gene, a B3GNT6 gene, or any combination of these, within the tissue of a patient having been diagnosed as having a glioma. These genes have been characterized as being expressed in relatively lower levels in the tumor of a glioma-afflicted patient, compared to higher levels identified in normal, non-glioma brain tissue. Therefore, as part of the present embodiment of the method, a patient having been diagnosed or suspected to have a glioblastoma would be treated so as to achieve an elevated level of expression of a selected non-glioma associated gene or genes, such as those listed in Table 3, or in particular embodiments, the MAN2A2 gene, the ST6GALNAC5 gene, the ST6GAL1 gene, the OGT gene, the B3GNT6 gene, or any combination of these. By way of example, this would be accomplished by administering an adenoviral vector particle having a sequence encoding a selected non-glioma associated target gene or genes, such as the MAN2A2 gene, the ST6GALNAC5 gene, the ST6GAL1 gene, the OGT gene, the B3GNT6 gene, or any combination of these, to a patient having been diagnosed with a glioma, and enhancing expression levels and/or reducing inhibition of expression of one or more of the selected target non-glioma associated genes in the patient so as to achieve non-glioma associated gene expression levels of the selected glioma-associated target gene or genes in the patient. For example, and in one embodiment, the treatment would provide the patient with a non-glioma associated gene expression level of the selected non-glioma associated target genes, MAN2A2, ST6GALNAC5, ST6GAL1, OGT, B3GNT6, or any combination of these. [0021] By way of example, a sufficient expression level of these genes would comprise an expression level that is characteristic of a normal, non-glioblastoma, brain tissue culture. [0022] Method for Detecting, Screening and/or Diagnosing Glioma in a Patient^ The present invention further provides a method for screening a tissue for glioblastoma, comprising measuring a brain tissue specimen for levels of expression of a gene selected from a group of genes comprising 2 or more of the genes: MAN2A2 gene, ST6GALNAC5 gene, ST6GAL1 gene, OGT gene, B3GNT6 gene, POFUTl gene, CHBLl gene, or ST3GAL3 gene. All or any combination of these genes may be examined for expression level within the brain tissue specimen. Any method for detection of the expression level of the identified gene product may be utilized, including but not limited to assays for the presence or activity of the glycogene protein within a cell or assays for detecting nucleic acids encoding or involved in the expression of a glycogene. Detection of a nucleic acid encoding a glycogene may be accomplished by detection of glycogene mRNA using any of several techniques available to one skilled in the art such as Northern blot (Alwine, et al. Proc. Natl. Acad. Sci. 74:5350), RNase protection (Melton, et al. Nuc. Acids Res. 12:7035), or RT-PCR (Berchtold, et al. Nuc. Acids. Res. 17:453). In one embodiment, the gene comprises MAN2A2, ST6GALNAC5, ST6GAL1, OGT, B3GNT6, POFUTl, CHI3L1, ST3GAL3 or any one or combination thereof. [0023] A Kit: In yet another embodiment, the present invention comprises a for determining the tumorigenicity or malignancy of a brain tumor. The kit may comprise a

panel of independent or paired nucleic acid molecules (such as any 1, 2 or more of the 45-mer

oligonucleotides provided in Table 1, such as the 45 mer that corresponds to detection of POFUTl gene activity, CHI3L1 gene activity, ST3GAL3 gene activity, or all of these) specific for the detection of the expression of specific nucleic acid sequences corresponding to specific glioma and/or non-glioma associated genes. One embodiment of such a kit utilizes -mediated nucleic acid amplification such as the polymerase chain reaction (PCR) in which a pair of nucleic acid molecules (i.e., primers) that allow for amplification of a nucleic acid sequence, are included. A kit allowing for determining levels of expression of these genes may be utilized to predict or determine tumorigenicity of a patient tumor biopsy sample. [0024] As is apparent to one of ordinary skill in the art, nucleic acid samples used in the methods and assays of the invention may be prepared by any available method or process. Methods of isolating total mRNA are well known to those of skill in the art. For example, methods of isolation and purification of nucleic acids are described in detail in Chapter 3 of Laboratory Techniques in Biochemistry and Molecular Biology, Vol. 24, Hybridization With Nucleic Acid Probes: Theory and Nucleic Acid Probes, P. Tijssen, Ed., Elsevier Press, New York, 1993. Such samples include RNA samples, but also include cDNA synthesized from a mRNA sample isolated from a cell or tissue of interest. Such samples also include DNA amplified from the cDNA, and RNA transcribed from the amplified DNA. One of skill in the art would appreciate that it is desirable to inhibit or destroy RNase present in homogenates before homogenates are used. [0025] The following definitions are used throughout the description of the present invention. [0026] As used here, a "glioma associated gene expression profile" is understood to mean an elevated level of expression of 2 or more glioma associated genes. For example, an elevated level of glioma-associated gene expression would include an expression level of these genes that is 1.5 fold greater than the gene expression level of the same genes by a normal (non-glioma) human brain cell culture. By way of example, 3 glioma-associated genes are POFUTl, CHBLl, and ST3GAL3. [0027] As used here, a "non-glioma associated gene expression profile" is understood to mean a gene expression level of 2 or more non-glioma-associated genes that is not less than about 80% the expression level of the same 2 or more non-glioma associated genes by a non-glioma human brain cell culture, a gene expression level of 2 or more glioma associated genes that is not more than about 20% greater than the expression level of the same 2 or more glioma associated genes by a non-glioma human brain cell culture, or both. By way of example, 5 non-glioma associated genes are MAN2A2, ST6GALNAC5, ST6GAL1, OGT, and B3GNT6. By way of example, 3 glioma-associated genes are POFUTl, CH13L1, and ST3GAL3. [0028] As used here, a "glioma associated gene" is a gene that encodes one or more of the glioma-associated genes POFUTl, CHI3L1, ST3GAL3, or any combination of the glioma associated genes in Table 2. [0029] As used here, a "non-glioma associated gene" is a gene that encodes one or more of the non-glioma-associated genes selected from the group consisting of 2 or more of MAN2A2, ST6GALNAC5, ST6GAL1, OGT, and B3GNT6, or any combination of the non- glioma associated genes in Table 3. [0030] As used here, a panel of glioma associated genes is understood to mean a panel of differentially expressed genes comprising one or more glioma associated genes, one or more non-glioma associated genes, or a combination thereof, that present a differentially identifiable expression profile compared to a non-glioma brain tissue culture of the same genes. In some embodiments, the panel of glioma associated genes comprises a MAN2A2 gene, a ST6GALNAC5 gene, a ST6GAL1 gene, a OGT gene, a B3GNT6 gene, or any combination of two or more of these genes. [0031] As used here, the term "bind(s) to" or "hybridizes to" refers to complementary hybridization between a probe nucleic acid (or oligonucleotide) and a target nucleic acid and embraces minor mismatches that can be accommodated by reducing the stringency of the hybridization media to achieve the desired detection of the target polynucleotide sequence

BRIEF DESCRIPTION OF THE FIGURES [0032] Figure 1: Statistical Analysis of the Microarray Data (a) SAM analysis of normalized expression data from six selected GBMs (red) versus six age-matched normal brain specimens (green) (b) Transformed data derived from SAM analysis at a false discovery rate (FDR) = 0%. The fold-change represented as a log ratio is plotted against the SAM (d) score, indicative of the significance of change. Thus, the largest most significant changes lie in the upper left- and upper right-most quadrants of the plot. [0033] Figure 2 : qRT-PCR corroboration of selected glyco-targets identified by microarray analysis. For each mRNA, transcript abundance, normalized to GAPDH, was calculated by qRT-PCR, as described in Materials and methods. Data are presented for MAN2A2 (panel 2a), ST6GALNAC5 (panel 2b), POFUTl (panel 2c), and CHI3L1 (panel 2d) and represent mean (±SD). Significant differences between GBM and normal brain were observed for all genes (* p < 0.05, ** p < 0.01, *** p < 0.001; two-tailed, unpaired student's t-test). n/s, not significant (p > 0.05).

DETAILED DESCRIPTION [0034] Within this application, unless otherwise stated, the techniques utilized may be found in any of several well-known references including: Molecular Cloning: A Laboratory Manual (Sambrook, et al., 1989, Cold Spring Harbor Laboratory Press), Gene Expression Technology (Methods in Enzymology, Vol. 185, edited by D. Goeddel, 1991. Academic Press, San Diego, Calif), PCR Protocols: A Guide to Methods and Applications (Innis, et al. 1990. Academic Press, San Diego, Calif), Culture of Animal Cells: A Manual of Basic Technique, 2.sup.nd Ed. (R. I. Freshney. 1987. Liss, Inc. New York, N.Y.), and Gene Transfer and Expression Protocols, pp. 109-128, ed. E. J. Murray, The Humana Press Inc., Clifton, N.J.). [0035] In practicing the present invention, it is advantageous to transfect into a cell a nucleic acid construct directing expression of a protein or nucleic acid product having the ability to alter expression of a glycogene. There are available to one skilled in the art multiple viral and non-viral methods suitable for introduction of a nucleic acid molecule into a target cell. Genetic manipulation of primary tumor cells has been described previously (Patel et al., 1994). Genetic modification of a cell may be accomplished using one or more techniques well known in the gene therapy field (Human Gene Therapy April 1994, Vol. 5, p. 543-563; Mulligan, R. C. 1993). Viral transduction methods may comprise the use of a recombinant DNA or RNA virus comprising nucleic acid sequence that drives or inhibits the expression of a protein having glyco-related protein, while retaining sufficient activity to infect a target cell. A suitable DNA virus for use in the present invention includes but is not limited to an adenovirus (Ad), adeno-associated virus (AAV), herpes virus, vaccinia virus or a polio virus. A suitable RNA virus for use in the present invention includes but is not limited to a retrovirus or Sindbis virus. It is to be understood by those skilled in the art that several such DNA and RNA viruses exist that may be suitable for use in the present invention. [0036] Adenoviral vectors have proven especially useful for gene transfer into eukaryotic cells (Stratford-Perricaudet and Perricaudet. 1991). Adenoviral vectors have been successfully utilized to study eukaryotic gene expression (Levrero, M., et al. 1991), vaccine development (Graham and Prevec, 1992), and in animal models (Stratford-Perricaudet, et al. 1992.; Rich, et al. 1993). The first trial of Ad-mediated gene therapy in human was the transfer of the cystic fibrosis transmembrane conductance regulator (CFTR) gene to lung (Crystal, et al., 1994). Experimental routes for administrating recombinant Ad to different tissues in vivo have included intratracheal instillation (Rosenfeld, et al. 1992) injection into muscle (Quantin, B., et al. 1992), peripheral intravenous injection (Herz and Gerard, 1993) and stereotactic inoculation to brain (Le Gal La Salle, et al. 1993). The adenoviral vector, then, is widely available to one skilled in the art and is suitable for use in the present invention. [0037] Adeno-associated virus (AAV) has recently been introduced as a gene transfer system with potential applications in gene therapy. Wild-type AAV demonstrates high-level infectivity, broad host range and specificity in integrating into the host cell genome (Hermonat and Muzyczka 1984). Herpes simplex virus type-1 (HSV-I) is attractive as a vector system for use in the nervous system because of its neurotropic property (Geller and Federoff. 1991; Glorioso, et al. 1995). Vaccinia virus, of the poxvirus family, has also been developed as an expression vector (Smith and Moss, 1983; Moss, 1992). Each of the above- described vectors is widely available to one skilled in the art and would be suitable for use in the present invention. [0038] Retroviral vectors are capable of infecting a large percentage of the target cells and integrating into the cell genome (Miller and Rosman. 1989). Retroviruses were developed as gene transfer vectors relatively earlier than other viruses, and were first used successfully for gene marking and transducing the cDNA of adenosine deaminase (ADA) into human lymphocytes. [0039] It is also possible to produce a viral vector in vivo by implantation of a "producer cell line" in proximity to the target cell population. As demonstrated by Oldfield, et al. (1993), infiltration of a brain tumor with cells engineered to produce a viral vector carrying an effector gene results in the continuous release of the viral vector in the vacinity of the tumor cells for an extended period of time (i.e, several days). In such a system, the vector is retroviral vector which preferentially infects proliferating cells, which, in the brain, would include mainly tumor cells. The present invention provides a methodology with which a viral vector supplies a nucleic acid sequence encoding a protein having glyco-related activity to cells involved in a neurological disorder such as brain cancer. [0040] "Non-viral" delivery techniques that have been used or proposed for gene therapy include DNA-ligand complexes, adenovirus-ligand-DNA complexes, direct injection of DNA, CaPO precipitation, gene gun techniques, electroporation, and lipofection (Mulligan, 1993). Any of these methods are widely available to one skilled in the art and would be suitable for use in the present invention. Other suitable methods are available to one skilled in the art, and it is to be understood that the present invention may be accomplished using any of the available methods of transfection. Several such methodologies have been utilized by those skilled in the art with varying success (Mulligan, R. 1993). Lipofection may be accomplished by encapsulating an isolated DNA molecule within a liposomal particle and contacting the liposomal particle with the cell membrane of the target cell. Liposomes are self-assembling, colloidal particles in which a lipid bilayer, composed of amphiphilic molecules such as phosphatidyl seine or phosphatidyl choline, encapsulates a portion of the surrounding media such that the lipid bilayer surrounds a hydrophilic interior. Unilammellar or multilammellar liposomes can be constructed such that the interior contains a desired chemical, drug, or, as in the instant invention, an isolated DNA molecule. [0041] The cells may be transfected in vivo (preferably at the tumor site), ex vivo (following removal from a primary or metastatic tumor site), or in vitro. The cells may be transfected as primary cells isolated from a patient or as a cell line derived from primary cells, and are not necessarily autologous to the patient to whom the cells are ultimately administered. Following ex vivo or in vitro transfection, the cells may be implanted into a host, preferably a patient having a neurological disorder and even more preferably a patient having a brain tumor. Genetic manipulation of primary tumor cells has been described previously (Patel et al. 1994). Genetic modification of the cells may be accomplished using one or more techniques well known in the gene therapy field (Human Gene Therapy. April 1994. Vol. 5, p. 543-563; Mulligan, R. C. 1993). [0042] In order to obtain transition of the nucleic acid of the present invention within a target cell, a transcriptional regulatory region capable of driving gene expression in the target cell is utilized. The transcriptional regulatory region may comprise a promoter, enhancer, silencer or repressor elements and is functionally associated with a nucleic acid of the present invention. Preferably, the transcriptional regulatory region drives high level gene expression in the target cell. It is further preferred that the transcriptional regulatory region drives transcription in a cell involved in a neurological disorder such as brain cancer. Transcriptional regulatory regions suitable for use in the present invention include but are not limited to the human cytomegalovirus (CMV) immediate-early enhancer/promoter, the SV40 early enhancer/promoter, the JC polyomavirus promoter and the chicken beta-actin promoter coupled to the CMV enhancer (Doll, et al. 1996). [0043] The vectors of the present invention may be constructed using standard recombinant techniques widely available to one skilled in the art. Such techniques may be found in common molecular biology references such as Molecular Cloning: A Laboratory Manual (Sambrook, et al., 1989, Cold Spring Harbor Laboratory Press), Gene Expression Technology (Methods in Enzymology, Vol. 185, edited by D. Goeddel, 1991. Academic Press, San Diego, Calif), and PCR Protocols: A Guide to Methods and Applications (Innis, et al. 1990. Academic Press, San Diego, Calif). Examples of nucleic acid constructs useful for practicing the present invention comprise a transcriptional regulatory region such as the CMV immediate-early enhancer/promoter, the SV40 early enhancer/promoter, the JC polyomavirus promoter, or the chicken beta-actin promoter coupled to the CMV enhancer operably linked to a nucleic acid encoding a glyco-related enzyme that is preferably MAN2A2, ST6GALNAC5, ST6GAL1, OGT, B3GNT6. To generate such a construct, a nucleic acid sequence encoding the enzyme may be processed using one or more restriction such that certain sequences flank the nucleic acid. Processing of the nucleic acid may include the addition of linker or adapter sequences. A nucleic acid sequence comprising a preferred transcriptional regulatory region may be similarly processed such that the sequence has flanking sequences compatible with the nucleic acid sequence encoding the enzyme. These nucleic acid sequences may then be joined into a single construct by processing of the fragments with an enzyme such as DNA ligase. The joined fragment, comprising a transcriptional regulatory region operably linked to a nucleic acid encoding a glyco-related enzyme, may then be inserted into a plasmid capable of being replicated in a host cell by further processing using one or more restriction enzymes. Alternatively, vectors containing nucleic acid sequences encoding antisense molecules designed to inhibit POFUTl, CH13Ll, or ST3GAL3 are envisioned and may be similarly constructed. [0044] Administration of a nucleic acid of the present invention to a target cell in vivo may be accomplished using any of a variety of techniques well known to those skilled in the art. Such reagents may be administered by intravenous injection or using a technique such as stereotactic injection to administer the reagent into the target cell or the surrounding areas (Badie, et al. 1994; Perez-Cruet, et al. 1994; Chen, et al. 1994; Oldfϊ eld, et al. 1993; Okada, et al. 1996). [0045] The vectors of the present invention may be administered orally, parentally, by inhalation spray, rectally, or topically in dosage unit formulations containing conventional pharmaceutically acceptable carriers, adjuvants, and vehicles. The term parenteral as used herein includes, subcutaneous, intravenous, intramuscular, intrasternal, infusion techniques or intraperitoneally. Suppositories for rectal administration of the drug can be prepared by mixing the drug with a suitable non-irritating excipient such as cocoa butter and polyethylene glycols that are solid at ordinary temperatures but liquid at the rectal temperature and will therefore melt in the rectum and release the drug. [0046] The dosage regimen for treating a neurological disorder disease with the vectors of this invention and/or compositions of this invention is based on a variety of factors, including the type of disease, the age, weight, sex, medical condition of the patient, the severity of the condition, the route of administration, and the particular compound employed. Thus, the dosage regimen may vary widely, but can be determined routinely using standard methods. [0047] The pharmaceutically active compounds (i.e., vectors, selected candidate compounds) of this invention can be processed in accordance with conventional methods of pharmacy to produce medicinal agents for administration to patients, including humans and other mammals. For oral administration, the pharmaceutical composition may be in the form of, for example, a capsule, a tablet, a suspension, or liquid. The pharmaceutical composition is preferably made in the form of a dosage unit containing a given amount of DNA or viral vector particles (collectively referred to as "vector"). For example, these may contain an amount of vector from about 103 -10 15 viral particles, preferably from about 106 -10 12 viral particles. A suitable daily dose for a human or other mammal may vary widely depending on the condition of the patient and other factors, but, once again, can be determined using routine methods. The vector may also be administered by injection as a composition with suitable carriers including saline, dextrose, or water. [0048] Injectable preparations, such as sterile injectable aqueous or oleaginous suspensions, may be formulated according to the known are using suitable dispersing or wetting agents and suspending agents. The sterile injectable preparation may also be a sterile injectable solution or suspension in a non-toxic parenterally acceptable diluent or solvent, for example as a solution in 1,3-butanediol. Among the acceptable vehicles and solvents that may be employed are water, Ringer's solution, and isotonic sodium chloride solution. In addition, sterile, fixed oils are conventionally employed as a solvent or suspending medium. For this purpose any bland fixed oil may be employed, including synthetic mono- or diglycerides. In addition, fatty acids such as oleic acid find use in the preparation of injectables. [0049] A suitable topical dose of active ingredient of a vector of the present invention is administered one to four, preferably two or three times daily. For topical administration, the vector may comprise from 0.001% to 10% w/w, e.g., from 1% to 2% by weight of the formulation, although it may comprise as much as 10% w/w, but preferably not more than 5% w/w, and more preferably from 0.1% to 1% of the formulation. Formulations suitable for topical administration include liquid or semi-liquid preparations suitable for penetration through the skin (e.g., liniments, lotions, ointments, creams, or pastes) and drops suitable for administration to the eye, ear, or nose. [0050] The pharmaceutical compositions may be made up in a solid form (including granules, powders or suppositories) or in a liquid form (e.g., solutions, suspensions, or emulsions). The pharmaceutical compositions may be subjected to conventional pharmaceutical operations such as sterilization and/or may contain conventional adjuvants, such as preservatives, stabilizers, wetting agents, emulsifϊ ers, buffers etc. Solid dosage forms for oral administration may include capsules, tablets, pills, powders, and granules. In such solid dosage forms, the active compound may be admixed with at least one inert diluent such as sucrose, lactose, or starch Such dosage forms may also comprise, as in normal practice, additional substances other than inert diluents, e.g., lubricating agents such as magnesium stearate. In the case of capsules, tablets, and pills, the dosage forms may also comprise buffering agents. Tablets and pills can additionally be prepared with enteric coatings. Liquid dosage forms for oral administration may include pharmaceutically acceptable emulsions, solutions, suspensions, syrups, and elixirs containing inert diluents commonly used in the art, such as water. Such compositions may also comprise adjuvants, such as wetting sweetening, flavoring, and perfuming agents. [0051] While the nucleic acids and/or vectors of the invention can be administered as the sole active pharmaceutical agent, they can also be used in combination with one or more vectors of the invention or other agents. When administered as a combination, the therapeutic agents can be formulated as separate compositions that are given at the same time or different times, or the therapeutic agents can be given as a single composition. [0052] The present invention may comprise elevation or depression of enzyme levels in cells expressing various amounts of enzyme. Introduction of a glycogene expression vector into a cell already expressing a high level of that enzyme may alter glycosylation patterns within that cell. Similarly, introduction of a nucleic acid construct that inhibits expression of such an enzyme in a cell expressing low levels of that enzyme may also serve to alter glycosylation patterns in that cell. Either of these methodologies may decrease the tumorigenicity of the cell by any of multiple mechanisms. [0053] The reagents and methodologies of the present invention may be utilized to treat or prevent brain cancer are provided herein Brain cancer is defined herein as any cancer involving a cell of neural origin, as well as cells of non-neural origin that have metastasized to the brain. Examples of brain cancers include but are not limited to intracranial neoplasms such as those of the skull (i.e., osteoma, hemangioma, granuloma, xanthona, osteitis deformans), the meninges (i.e., meningioma, sarcoma, gliomatosis), the cranial nerves (i.e., glioma of the optic nerve, schwannoma), the neuroglia (i.e., gliomas) and ependyma (i.e., ependymomas), the pituitary or pineal body (i.e., pituitary adenoma, pinealoma), and those of congenital origin (i.e., craniopharygioma, chordoma, germinoma, teratoma, dermoid cyst, angioma, hemangioblastoma), as well as those intracranial neoplasms of metastatic origin, including, but not restricted to, primary tumors arising in colon, breast, lung and prostate. [0054] The following Examples are for illustrative purposes only and are not intended, nor should they be construed as limiting the invention in any manner. Those skilled in the art will appreciate that variations and modifications can be made without violating the spirit or scope of the invention. Example 1: Materials and Methods [0055] The present example is provided to detail the materials and methods used in the studies described herein. [0056] Human Tissue Samples: For the microarray analysis, six surgical specimens and six normal human brain specimens were used. For the qRT-PCR analyses, four additional glioblastoma and four additional normal brain specimens were used. [0057] Brain tumor tissue (GBM, WHO Grade IV) from patients was acquired from Field Neurosciences Institute, Saginaw, MI and from the tumor bank maintained by the FaIk Center. None of the patients had been subjected to chemotherapy or radiotherapy prior to resection. Protocols for tissue accrual and use were approved by the appropriate Institutional Review Boards. Immediately upon resection, tissue was stored in KNAlater RNA Stabilization Reagent (Qiagen, Valencia, CA, USA) and subsequently snap frozen and maintained in liquid nitrogen. All tissue samples used in these analyses were evaluated by a neuropathologist; all specimens selected were characterized by dense tumor cellularity and the presence of >90% tumor tissue. The average patient age at time of resection was 56.1 (±13.1) years. There were six males and four females represented, and the mean survival was 8.7 (±3.0) months from time of diagnosis. [0058] Normal brain tissue was obtained from representative tissue punches of gray matter from 10 appropriately age-matched hemicoronal brain tissue sections obtained from autopsy specimens provided by the Brain and Tissue Bank for Developmental Disorders at the University of Maryland, Baltimore, Maryland. All tissue sections were maintained in liquid nitrogen. The average age at time of death was 58.0 (±7.6) years. There were seven males and three females represented, and the mean post mortem interval for sample preservation was 17.2 (±5.4) h. [0059] Human Glioma Cell Culture: The following cell lines were used for qRT-PCR analysis: human glioblastomas, SNB19 and D54MG, U87MG, U373MG, U l 18MG, U25 1, and A172 (obtained from ATCC, Rockville, MD, USA). All established human brain tumor cell lines were maintained using Dulbecco's modified Eagle's medium (containing 4.5 g/L glucose) supplemented with 10% heat-inactivated fetal bovine serum (Whittaker BioProducts, Walkersville, MD, USA). [0060] Microarray fabrication, validation, and quality control: The 359 genes comprising the present focused Human Glycobiology microarray are compiled from NCBI/EMBL/TIGR human sequence databases and the Consortium for Functional Glycomics-CAZY databases (available at http://www.cazy.org/CAZY/) and represented all of the cloned human glycogenes, glycosylhydrolases, polysaccharide lyases, and carbohydrate esterases. Only those genes with fully curated Reference Sequence (RefSeq) ID's were used. Individual 45-mer oligonucleotide complementary to sequences within these human mRNAs were designed and prioritized using stringent selection criteria, including minimal secondary structure, minimal homology to other genes in the available human genomic databases, no low complexity or repeat regions, and all with a similar, yet well-defined Tm [ArrayDesigner v2.03, Premier Biosoft, Palo Alto, CA, USA] to provide optimal hybridization efficiency across all oligos on the array. Control oligonucleotides representing the most traditionally accepted and commonly utilized housekeeping genes (Lee et al. 2002) were similarly designed and prioritized. [0061] Among the 359 genes comprising the focused Human Glycobiology microarray, the following panel of 45-mer oligonucleotides were synthesized: Table 4 Oligonucleotide Sequence used on Microarray 5' CAAATATTCTGGGGTTGAGGGAAATTGCTGCTGTCTACAAAATGC 3' 5' GAGCCAAACATCCTACAAGACACAGTGACCATACTAATTATACCC 3' 5' CCTGGCTTCTAGATCTGGAACCTTACCACGTTACTGCATACTGAT 5' CGTTATCATTGGTCTGGTGAGATGTTTCATATTTGTGACAGTTAA 3' 5' CCAGATCAGTCAGAGCCCCTACAGCATTGTTAAGAAAGTATTTGA 3' 5' TAGTGTATCATGTTTTCCCTGTTGGTATGTAGCCTGGATAAATGC 3' 5' TCCCTGTATAGAAATGTGGAATTGTCCCTTTGTAGCCAACTATAA 3' 5' CACTCCATATATTCAGCATCGTCAGAGAAACCCAAATCAGCCATT 3' 5' ATGCTAAGGAACACCACATGCCATTATTAACTTCACATTCTACAA 3' 5' CATCTACTTGGCAAGGTCATAGACAATTCCTCCAGAGACACTGAG 3' 5' GGACCTCGTCTTTATGAAACACACACCTGGAATAAAACCACTTCT 3' 5' CAGCATAATGATTTGAGATTGGTCCATGTTGTGTGATTCAGTGGT 3' 5' CTTTGTGAGCCGTGTCGTATGACCTAGTAAACTTTGTACCAATTC 3' 5' AATCATCCAGTCATTCCAATGGCAAATAAGTTCTCACCTACCCTT 3' 5' AAGAAAGTGAAATGAGCCGACAGCCCAGGTGATAGAAATAAATTG 3' 5' CCCCATACCCTCACCCTTAAAATTCTCCTGTAACTCAACTAACAA 3' 5' GGTTCACCCACCTGGAGCTGGAATTATCACTTCCGAAATAAAGCG 3' 5' CAGTTCTGAAGATTCACGTATCCATCTGGAGACCTACAGGAAGAA 3' 5' TAAAGAGTCAGACGCCACAGGCATTCCCATTAAAGTCAGAAACTA 3' 5' CTGGGCTGGGTATGTGCCTACCGATGACAATGTGTAAATAAATGC 3' 5' GGTTTTATCTTGGCTTTTAGTAATCATGTTGGCTGGTCTGGTCAC 3' 5' GTGACTGCCCCAGACTTGGTTTTGTAATGATTTGTACAGGAATAA 3' 5' CTCAGTCCAGAGACCTAACATTCAGAATATAGCATTGGTTGCCTA 3' 5' TTTGAACAACTGACTCTTGATGGACACAACCTTCCTTCTCTCGTC 3' 5' TATGTGTGGCATCCATGTTGGTTTCGTCTGTCTGTAATGTGAATT 3' 5' CCTCACGGCCGATGCTCTGCAGTCTGACAAGCTTCAGACCTGGAC 3' 5' TGGTAATTTATCCTTCCTAACTCTTTAATCCTGAATGATGGTTGG 3' 5' GAGGACCTGACCCTACTCCCTTGCCCTAGATAGTTTATTATTATT 3' 5' AATACCCACACTTACCTTAATACAAACATCCCAGCAACAGCACAT 3' 5' CTCAGTCCAGAGACCTAACATTCAGAATATAGCATTGGTTGCCTA 3' 5' CTGCCCTCCGCCATCCCTGCTATTTAAATTATTTAAGGTCTCTGG 3' 5' CTGAGGAGCAGCTGTTCTGATGCACGGGAACAAGCAGCACCTGCA 3' 5' CTTATGGGAGCTGGCACGTCACCCACAGCCTGGCAGCTCTGATCA 3' 5' AAAAGCTTATGGGAGCTGGCACGTCACAAAAAGAAAAAAACCAAG 3'

[0062] These optimal oligonucleotides were individually synthesized with the addition of a 5'-amino linker (C6-TFA, Glen Research, Sterling, VA, USA) onto each oligonucleotide, as described (Kroes et al. 2006). The oligonucleotides were then robotically arrayed, covalently linked in quadruplicate to aldehyde-coated glass microscope slides, and quality controlled prior to use. [0063] The dynamic range, discrimination power, accuracy, reproducibility, and specificity of the focused oligonucleotide microarrays used in these studies were evaluated by exogenous mRNA spiking studies. Exogenous mRNA spiking studies were conducted as described in Kroes et al, 2006), which reference is specifically incorporated herein by reference for this purpose. The dynamic range, defined as the range of transcript abundance over which hybridization intensity was linearly correlated, was identified in six independent experiments and was found to be between two and three orders of magnitude. The data presented here fell within this dynamic range. Discrimination power, or the ability to discriminate authentic signal from background at the low end of the dynamic range, was also used here to set appropriate cutoffs prior to statistical analysis of the data. The reproducibility of both the raw, preprocessed data and appropriately normalized data was determined by comparison of the coefficients of variation across all levels of expression for each exogenous transcript, and was typically CV = 0.09. The accuracy of the microarray results was determined by direct comparison to individual mRNA abundance determined by qRT-PCR analysis of the spiked mRNA samples. Conformity between the two datasets (i.e., qRT-PCR and the spiked microarray samples) was measured, with a Pearson correlation coefficient of +0.96, which is in good agreement with reported values (Baum et al. 2003). [0064] Hybridization specificity was evaluated using a range of 1-6 sequence mismatches synthesized within the gene-specific 45-mer oligonucleotide immobilized on the array. The oligonucleotides used on the microarrays were gene specific since adverse effects on hybridization efficiency were not found with less than three mismatches. Example 2 : Target Preparation; RNA Extraction and Labeling, and Microarray Hybridization [0065] Total RNA was extracted from tissues with guanidine isothiocyanate and CsCl-ultracentrifugation, purified (Qiagen) and used as the substrate for RNA amplification and labeling, exactly as described (Kroes et al. 2006). A universal human reference RNA (Stratagene, La Jolla, CA, USA) was used in the present analyses. Identical aliquots were treated concurrently with the tissue samples. Equivalent amounts of Cy5-labeled (experimental) and purified Cy3-labeled (reference) amplified RNA (aRNA) targets (each labeled to 15-18% incorporation) were combined, denatured and hybridized at 46°C for 16 h. Following sequential high-stringency washes, individual Cy3 and Cy5 fluorescence hybridization to each spot on the microarray was quantitated by a high resolution confocal laser scanner. [0066] Data Acquisition and Statistical Analysis: Arrays were scanned (at 633 and 543 nm) at 5 µm resolution on the ScanArray 4000XL (Packard Biochip Technologies, Billerica, MA, USA) utilizing QuantArray software [v3.0] at the maximal laser power that produced no saturated spots. The adaptive threshold method was used to differentiate the spot from the background and spot intensity determined using median pixel intensity. Prior to normalization, quality confidence measurements (spot diameter, spot area, array footprint, spot circularity, signal: noise ratio, spot uniformity, background uniformity, and replicate uniformity) were calculated for each scanned array and spots were flagged that did not pass stringent selection criteria. The data from each channel were normalized using the LOWESS curve-fitting equation on a print-tip specific basis (GeneTraffic v2.8, Iobion Informatics, La Jolla, CA, USA). Statistical analyses were performed using the permutation-based SAM (significance analysis of microarrays) algorithm (v2.20, Stanford University, see Tusher et al., 2001), that reports the median false discovery rate (FDR) as the percentage of genes in the identified gene list (rather than in the entire cohort of genes present on the microarray) that are falsely reported as showing statistically significant differential expression. In our analyses, appropriately normalized data were analyzed utilizing the two class, unpaired analysis utilizing a minimum of 1000 permutations and was performed comparing expression data derived from glioblastomas (GBMs) vs. normal brain. The cutoff for significance in these experiments was set at a 0% FDR at a specified 1.5-fold change. [0067] Quantitative real-time PCR analysis: The expression levels of selected genes were analyzed by real-time PCR using Brilliant SYBR Green qRT-PCR Master Mix (Strata-gene) on an Mx3000P Real-Time PCR System (Stratagene, La Jolla, CA, USA). Reverse transcription of 1 µg of DNAsed, total RNA was primed with oligo(dT) and random hexamers and was performed exactly as described (Kroes et al. 2006). All primer sets were designed across intron:exon boundaries to derive -100 bp amplicons (Table 1), with individual primer concentrations and final amplification conditions optimized for each gene. Dissociation curves were performed on all reactions to assure product purity. Original input RNA amounts were calculated by comparison to standard curves using purified PCR product as a template for the mRNAs of interest and were normalized to amount of glyceraldehyde-3 -phosphate dehydrogenase (GAPDH). Studies were performed in triplicate for each data point. Table 5 q RT-PCR primers used in the study

Gene ID Accession# Primers (forward, reverse) Amplicon size (bp)

MAN2A2 NM 006122 5'-TCAAGGACAACAAGAGAACC-S' 100 5'-GATGGGTAGCTGGTAG AGTG-3 ' POFUTl NM 015352 5'-AACAGCTCTTCAAAGGGAAG-S' 104 5'-ACAGTTGCCAATAAAGTGGT-S ' ST6GALNAC5 NM 030965 5'-TGGACGGATACCTCGGAGTG-S' 123 5'-TCTGTCTGGTCAATCTGGGAG-3 ' CH13L1 NM 001276 5'-TGATGTGACGCTCTACGGC-S' 161 5'-AATGGCGGTACTGACTTGATG-S ' GAPDH NM 002046 5'-ATGGGGAAGGTGAAGGTCG-S' 108 5'-GGGGTCATTGATGGCAACAATA-S ' Example 3: Focused Microarray Analysis Identified Aberrant Glyco-Gene Expression in GBMs [0068] The expression of 359 glyco-related genes was analyzed using the inventors' focused oligonucleotide microarray panel in diagnosed GBMs and in normal (non-glioma) tissue samples obtained from cortical sections from autopsy specimens. GBM (n = 6) and control (n = 6) RNA samples were studied in triplicate with three microarray slides for each sample. As each oligonucleotide is spotted in quadruplicate on the array, there are a total of 72 expression measurements for each gene in each group. To circumvent the inherent biological heterogeneity of clinical GBM specimens (Bigner et al. 1998), a universal reference design was employed (Churchill 2002) and comprehensive statistical analysis platforms to facilitate acquisition of expression profiles from a necessarily large number of biological and technical replicates. The tumor samples expressed between 77.3% and 86.7% of the genes present on the microarray. [0069] A SAM analysis was used to determine statistically significant differences in the measured expression levels for each gene on the array and demonstrated that a number of genes can be identified with high confidence as differentially expressed between the two cell types (Fig. 1). [0070] Table 6 shows the identities, functional annotations, and relative expression ratios of these differentially expressed genes. Of the 359 genes, 34 glyco-genes genes differed in their expression between GBM and normal brain by at least 1.5-fold (at 0% FDR). Importantly, at this stringent FDR, none of these changes was expected to be a false- positive. Of the 34 genes, 10 had increased and 24 had decreased measured expression levels in the grade IV tumors relative to normal brain. These differentially expressed transcripts fell into well-defined pathways for glycan biosynthesis and metabolism (Kanehisa et al. 2004; Table 2). Table 6 GBM associated transcri ts identified b microarra analvsis O.O% FDR

[0071] The expression pattern of four genes identified by stringent SAM analysis of the microarray data were further studied in a larger panel of tumors by quantitative real-time RT-PCR; α-mannosidase 2A2 (MAN2A2), protein O-fucosyltransferase 1 (POFUTl), ST6 (α-N-acetyl-neuraminyl-2,3-β-galactosyl 1,3) N-acetylgalactosaminide α2,6-sialyltransferase 5 (ST6GALNAC5), and chitinase 3-like 1 (CHI3L1). These genes represent key genes in N-glycan biosynthesis, O-glycan biosynthesis, ganglioside biosynthesis, and another glyco- related gene recently identified in high grade glioma. Example 4 : qRT-PCR Analysis Corroborated the Microarray Results [0072] Three (3) genes were chosen that have not been previously associated with GBM, as well as one gene found to be up-regulated in gliomas. mRNA levels were measured by real-time quantitative RT-PCR. The core approach to transcriptome profiling was to use the focused microarrays as a screening tool to identify statistically significant differentially expressed genes followed by corroboration of a subset of these in larger sample panels using higher throughput methodology, including quantitative qRT-PCR. As such, the number of samples was expanded for the qRT-PCR corroboration to analyze total RNA from 10 GBM samples, 10 age-matched normal brain controls, and seven glioma cell lines and the expression of MAN2A2, ST6GALNAC5, POFUTl and CHI3L1 was analyzed relative to the level of GAPDH mRNA in each sample. [0073] GAPDH was chosen for a reference (control) because its mRNA levels, measured by microarray analysis, were comparable between GBM and normal brain. [0074] Consistent with the microarray data, there was a measured significant down- regulation of MAN2A2 and ST6GALNAC5 mRNAs and significant up-regulation of POFUTl and CHI3L1 in the GBMs relative to normal (non-glioma) brain using qRT-PCR (Fig. 2). The glioma cell lines demonstrated comparable levels of MAN2A2, ST6GalNAc5, and POFUTl to those observed in the primary tumor specimens. Example 5 : Glycobiologv-based microarrays for novel Therapeutic Target Identification [0075] The steady-state expression of the oligosaccharides associated with a specific cell-surface glycoconjugate is the result of the concerted expression of all of the glycogenes involved in its biosynthesis and the glycosidases, involved in its degradation [84]. In a system as complex as brain tumorigenesis and invasion it seems as important to determine global context or pattern of these changes as it does to determine the aberrantly expressed, individual glyco-related gene changes found in such systems. Microarray-based approaches are rapidly becoming one of the cornerstone technologies in rapid throughput gene expression analyses and have made significant impact defining aberrant gene expression in a multitude of tumor systems [85-87]. [0076] The presently disclosed custom oligonucleotide microarrays were utilized to even further define the intrinsically complex regulation and activity of glyco-related genes. As genes encoding key glyco-related mRNAs are drastically underrepresented on most commercial arrays, a microarray core facility was created to provide a comprehensive platform of glycoconjugate metabolism-associated oligonucleotides assuring the most up-to- date coverage of these gene families. This technology has not been systematically applied to the global analysis of glyco-related gene expression in brain tumors. Production, hybridization and data analysis of the present oligonucleotide arrays have been optimized in order to measure subtle, phenotypically relevant changes in glyco-gene expression associated with brain tumorigenesis both in vitro and in vivo. [0077] The 359 genes comprising the present Human Glycobiology microarray are compiled from NCBI/EMBL/TIGR human sequence databases and the Consortium for Functional Glycomics-CAZY databases. Unique sense 45-mer oligonucleotides corresponding to mRNAs of each gene used as probes are individually synthesized, purified and immobilized via a 5'-amino linker onto aldehyde-coated microarrays. Total RNA is reverse transcribed and used as the substrate for RNA amplification and labeling using the indirect aminoallyl methodology based on the Eberwine protocol [89]. To circumvent the inherent biological heterogeneity of clinical GBM specimens [90], a universal reference design [91] was employed, and a comprehensive statistical analysis platform was used to facilitate acquisition of expression profiles from a necessarily large number of biological and technical replicates. The present high quality, application-specific, low density microarray platform provides an efficient strategy for such an endeavor. [0078] Initial microarray analyses comparing three Grade IV gliomas with three aged- matched normal brain specimens yielded 10 significant genes more highly expressed in gliomas compared to normal brain and 24 genes more highly expressed in normal brain compared to gliomas. There are demonstrated here to be many significant differences in expression of genes associated with glycoconjugate biosynthesis and degradation, all of them targets for therapeutics for the treatment of brain tumors. The presently disclosed oligonucleotides panels and gene expression profiles may be used to (1) analyze an increased the number of primary tumors, (2) evaluate and characterize additional human glioma cell lines by microarray analysis. Cell lines that have been transfected to include the glioblastoma associated gene or genes as identified here also provide an in vitro model systems for characterizing the regulation of a given gene or associated gene family, (3) confirm and extend the present microarray data with in situ hybridization studies and quantitative RT-PCR analyses, and (4) Continuing to evaluate therapeutic candidates using viral vectors in animal models such as the SCID mouse. [0079] The following table presents the 45-mer oligonucleotides : [0080] Group I : These unified 45 mers (SEQ ID Nos. 1-14) were designed, synthesized, and used to identify fourteen (14) glioma associated genes that are over expressed by at least 1.5- fold in human glioma tissue as compared to non-glioma, normal human brain tissue. (A) SEQ ID No. 1 (identifies FUT3) 5' CAAATATTCTGGGGTTGAGGGAAATTGCTGCTGTCTACAAAATGC 3' (B) SEQ ID No. 2 (identifies CHBLl) 5' GAGCCAAACATCCTACAAGACACAGTGACCATACTAATTATACCCS ' (C) SEQ ID No. 3 (identifies GYSI) 5' CCTGGCTTCTAGATCTGGAACCTTACCACGTTACTGCATACTGAT 3' (D) SEQ ID No. 4 (identifies SIATl, transcript variant 2) 5' CGTTATCATTGGTCTGGTGAGATGTTTCATATTTGTGACAGTTAA 3' (E) SEQ ID No. 5 (identifies EGFR) 5' CCAGATCAGTCAGAGCCCCTACAGCATTGTTAAGAAAGTATTTGA 3' (F) SEQ ID No. 6 (identifies POFUTl, transcript variant 1) 5' TAGTGTATCATGTTTTCCCTGTTGGTATGTAGCCTGGATAAATGC 3' (G) SEQ ID No. 7 (identifies GLT8D2) 5' TCCCTGTATAGAAATGTGGAATTGTCCCTTTGTAGCCAACTATAA 3' (H) SEQ ID No. 8 (identifies ST6GALII) 5' CACTCCATATATTCAGCATCGTCAGAGAAACCCAAATCAGCCATT 3' (I) SEQ ID No. 9 (identifies B3GALT3, transcript variant 2) 5' ATGCTAAGGAACACCACATGCCATTATTAACTTCACATTCTACAA 3' (J) SEQ ID No. 10 (identifies HYAL1, transcript variant 6) 5' CATCTACTTGGCAAGGTCATAGACAATTCCTCCAGAGACACTGAG 3' (K) SEQ ID No. 11 (identifies ST3GAL3) 5' TATGATCGGTTGGGCTTCCTCCTGAATCTGGACTCTAAACTCTCA 3' (L) SEQ ID No. 12 (identifies SIAT4C) 5' AGACGCCTACAACAAGAAGCAGACCATTCACTACTATGAGCAGATS '

(M) SEQ ID No. 13 (identifies HEXB) 5' GGCTTCCCTGTAATCCTTTCTGCTCCTTGGTACTTAGATTTGATT 3' (N) SEQ ID No. 14 (identifies MGAT3) 5' GAGGCGGAAGTCTAGAGCTGCATGATCTGATAGGGTTTGTGACAG 3'

[0081] Group II: These 45-mers (SEQ ID Nos. 15-42) were designed, synthesized and used to identify a selection of 28 genes that were more highly expressed in non-glioma human brain tissue by at least 1.5 fold as compared to non-glioma (normal) human brain tissue.

(O) SEQ ID No. 15 (identifies GALNTLl) 5' GGACCTCGTCTTTATGAAACACACACCTGGAATAAAACCACTTCT 3' (P) SEQ ID No. 16 (identifies GALC) 5' CAGCATAATGATTTGAGATTGGTCCATGTTGTGTGATTCAGTGGT 3' (Q) SEQ ID No. 17 (identifies HKl, transcript variant 1) 5' CTTTGTGAGCCGTGTCGTATGACCTAGTAAACTTTGTACCAATTC 3' (R) SEQ ID No. 18 (identifies MAN2A1) 5' AATCATCCAGTCATTCCAATGGCAAATAAGTTCTCACCTACCCTT 3' (S) SEQ ID No. 19 (identifies UGT8) 5' AAGAAAGTGAAATGAGCCGACAGCCCAGGTGATAGAAATAAATTG 3' (T) SEQ ID No. 20 (identifies OGT, transcript variant 3) 5' CCCCATACCCTCACCCTTAAAATTCTCCTGTAACTCAACTAACAA 3' (U) SEQ ID No. 2 1 (identifies EXTLl) 5' GGTTCACCCACCTGGAGCTGGAATTATCACTTCCGAAATAAAGCG 3' (V) SEQ ID No. 22 (identifies MDClD) 5' CAGTTCTGAAGATTCACGTATCCATCTGGAGACCTACAGGAAGAA 3' (W) SEQ ID No. 23 (identifies MAN2A2) 5' TAAAGAGTCAGACGCCACAGGCATTCCCATTAAAGTCAGAAACTA3' (X) SEQ ID No. 24 (identifies B3GNT6) 5' CTGGGCTGGGTATGTGCCTACCGATGACAATGTGTAAATAAATGC 3' (Y) SEQ ID No. 25 (identifies MGEA5) 5' GGTTTTATCTTGGCTTTTAGTAATCATGTTGGCTGGTCTGGTCAC 3' (Z) SEQ ID No. 26 (identifies ST6GALNAC6) 5' GTGACTGCCCCAGACTTGGTTTTGTAATGATTTGTACAGGAATAA 3' (AA) SEQ ID No. 27 (identifies B3GNT6) 5' CTCAGTCCAGAGACCTAACATTCAGAATATAGCATTGGTTGCCTA 3' (BB) SEQ ID No. 28 (identifies HMT-I) 5' TTTGAACAACTGACTCTTGATGGACACAACCTTCCTTCTCTCGTC 3' (CC) SEQ ID No. 29 (identifies NLGN4, transcript variant 1) 5' TATGTGTGGCATCCATGTTGGTTTCGTCTGTCTGTAATGTGAATT 3' (DD) SEQ ID No. 30 (identifies CAPN3, transcript variant 2) 5' CCTCACGGCCGATGCTCTGCAGTCTGACAAGCTTCAGACCTGGAC 3' (EE) SEQ ID No. 31 (identifies ST6GALNAC5) 5' TGGTAATTTATCCTTCCTAACTCTTTAATCCTGAATGATGGTTGG 3' (FF)SEQ ID No. 32 (identifies HYAL2, transcript variant 2) 5' GAGGACCTGACCCTACTCCCTTGCCCTAGATAGTTTATTATTATT 3' (GG) SEQ ID No. 33 (identifies B3GNT9) 5' AATACCCACACTTACCTTAATACAAACATCCCAGCAACAGCACAT 3' (HH) SEQ ID No. 34 (identifies BGATl , transcript variant 2) 5' CTCAGTCCAGAGACCTAACATTCAGAATATAGCATTGGTTGCCTA 3' (II) SEQ ID No. 35 (identifies GYLTLlB) 5' CTGCCCTCCGCCATCCCTGCTATTTAAATTATTTAAGGTCTCTGG 3' (JJ) SEQ ID No. 36 (identifies CAPN3, transcript variant 4) 5' CTGAGGAGCAGCTGTTCTGATGCACGGGAACAAGCAGCACCTGCA 3' (KK) SEQ ID No. 37 (identifies CAPN3, transcript variant 5) 5' CTTATGGGAGCTGGCACGTCACCCACAGCCTGGCAGCTCTGATCA 3' (LL) SEQ ID No. 38 (identifies CAPN3, transcript variant 6) 5' AAAAGCTTATGGGAGCTGGCACGTCACAAAAAGAAAAAAACCAAG 3' (MM) SEQ ID No. 39 (identifies ST6GAL1) 5' CGTTATCATTGGTCTGGTGAGATGTTTCATATTTGTGACAGTTAA 3' (NN) SEQ ID No. 40 (identifies FUCAl) 5' ACAATGGAATCTTCCCTCTGTTCTCTGATAACCTACTTGCTTACT 3' (00) SEQ ID No. 41(identifies MGATl) 5' TCCTTGCAGCCTAGCAGTTTATAGTTCTGAGATGGAAAGTTGAAG 3' (PP) SEQ ID No. 42 (identifies MGAT5) 5' CTTTGACCCTAAGAATAAGCACTGTGTGTTTCAAGGTGACCTCCT 3'

[0082] It should be understood that various changes and modifications to the presently preferred embodiments described herein will be apparent to those skilled in the art. Such changes and modifications can be made without departing from the spirit and scope of the present subject matter and without diminishing its intended advantages. It is therefore intended that such changes and modifications be covered by the appended claims. BIBLIOGRAPHY The following references are specifically incorporated herein in their entirety by reference:

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(A) SEQ ID No. 1: 5' CAAATATTCTGGGGTTGAGGGAAATTGCTGCTGTCTACAAAATGC 3'; (B) SEQ IDNo. 2: 5' GAGCCAAACATCCTACAAGACACAGTGACCATACTAATTATACCC 3'; (C) SEQ ID No. 3 5' CCTGGCTTCTAGATCTGGAACCTTACCACGTTACTGCATACTGAT 3'; (D) SEQ ID No. 4: 5' CGTTATCATTGGTCTGGTGAGATGTTTCATATTTGTGACAGTTAA 3'; (E) SEQ IDNo. 5: 5' CCAGATCAGTCAGAGCCCCTACAGCATTGTTAAGAAAGTATTTGA 3'; (F) SEQ ID No. 6: 5' TAGTGTATCATGTTTTCCCTGTTGGTATGTAGCCTGGATAAATGC 3'; (G) SEQ IDNo. 7: 5' TCCCTGTATAGAAATGTGGAATTGTCCCTTTGTAGCCAACTATAA 3'; (H) SEQ IDNo. 8: 5' CACTCCATATATTCAGCATCGTCAGAGAAACCCAAATCAGCCATT 3'; (I) SEQ IDNo. 9: 5' ATGCTAAGGAACACCACATGCCATTATTAACTTCACATTCTACAA 3'; (J) SEQ IDNo. 10: 5' CATCTACTTGGCAAGGTCATAGACAATTCCTCCAGAGACACTGAG 3'; (K) SEQ IDNo. 11: 5' TATGATCGGTTGGGCTTCCTCCTGAATCTGGACTCTAAACTCTCA 3'; (L) SEQ IDNo. 12: 5' AGACGCCTACAACAAGAAGCAGACCATTCACTACTATGAGCAGAT 3'; (M) SEQ IDNo. 13: 5' GGCTTCCCTGTAATCCTTTCTGCTCCTTGGTACTTAGATTTGATT 3'; (N) SEQ IDNo. 14: 5' GAGGCGGAAGTCTAGAGCTGCATGATCTGATAGGGTTTGTGACAG 3'; (O) SEQ IDNo. 15: 5' GGACCTCGTCTTTATGAAACACACACCTGGAATAAAACCACTTCT 3'; (P) SEQ IDNo. 16: 5' CAGCATAATGATTTGAGATTGGTCCATGTTGTGTGATTCAGTGGT 3'; (Q) SEQ IDNo. 17: 5' CTTTGTGAGCCGTGTCGTATGACCTAGTAAACTTTGTACCAATTC 3'; (R) SEQ IDNo. 18: 5' AATCATCCAGTCATTCCAATGGCAAATAAGTTCTCACCTACCCTT 3'; (S) SEQ IDNo. 19: 5' AAGAAAGTGAAATGAGCCGACAGCCCAGGTGATAGAAATAAATTG 3'; (T) SEQ IDNo. 20: 5' CCCCATACCCTCACCCTTAAAATTCTCCTGTAACTCAACTAACAA 3'; (U) SEQ IDNo. 21: 5' GGTTCACCCACCTGGAGCTGGAATTATCACTTCCGAAATAAAGCG 3'; (V) SEQ IDNo. 22: 5' CAGTTCTGAAGATTCACGTATCCATCTGGAGACCTACAGGAAGAA 3'; (W) SEQ IDNo. 23: 5' TAAAGAGTCAGACGCCACAGGCATTCCCATTAAAGTCAGAAACTA 3'; (X) SEQ ID No. 24: 5' CTGGGCTGGGTATGTGCCTACCGATGACAATGTGTAAATAAATGC 3'; (Y) SEQ IDNo. 25: 5' GGTTTTATCTTGGCTTTTAGTAATCATGTTGGCTGGTCTGGTCAC 3'; (Z) SEQ ID No. 26: 5' GTGACTGCCCCAGACTTGGTTTTGTAATGATTTGTACAGGAATAA 3'; (AA) SEQ ID No. 27: 5' CTCAGTCCAGAGACCTAACATTCAGAATATAGCATTGGTTGCCTA 3'; (BB) SEQ ID No. 28: 5' TTTGAACAACTGACTCTTGATGGACACAACCTTCCTTCTCTCGTC 3'; (CC) SEQ ID No. 29: 5' TATGTGTGGCATCCATGTTGGTTTCGTCTGTCTGTAATGTGAATT 3'; (DD) SEQ IDNo. 30: 5' CCTCACGGCCGATGCTCTGCAGTCTGACAAGCTTCAGACCTGGAC 3'; (EE) SEQ IDNo. 31: 5' TGGTAATTTATCCTTCCTAACTCTTTAATCCTGAATGATGGTTGG 3'; (FF) SEQ ID No. 32: 5' GAGGACCTGACCCTACTCCCTTGCCCTAGATAGTTTATTATTATT 3'; (GG) SEQ IDNo. 33: 5' AATACCCACACTTACCTTAATACAAACATCCCAGCAACAGCACAT 3'; (HH) SEQ ID No. 34: 5' CTCAGTCCAGAGACCTAACATTCAGAATATAGCATTGGTTGCCTA 3'; (II) SEQ IDNo. 35: 5' CTGCCCTCCGCCATCCCTGCTATTTAAATTATTTAAGGTCTCTGG 3'; (JJ) SEQ IDNo. 36: 5' CTGAGGAGCAGCTGTTCTGATGCACGGGAACAAGCAGCACCTGCA 3'; (KK) SEQ IDNo. 37: 5' CTTATGGGAGCTGGCACGTCACCCACAGCCTGGCAGCTCTGATCA 3'; (LL) SEQ IDNo. 38: 5' AAAAGCTTATGGGAGCTGGCACGTCACAAAAAGAAAAAAACCAAG 3'; (MM) SEQ ID No. 39: 5' CGTTATCATTGGTCTGGTGAGATGTTTCATATTTGTGACAGTTAA 3'; (NN) SEQ IDNo. 40: 5' ACAATGGAATCTTCCCTCTGTTCTCTGATAACCTACTTGCTTACT 3'; (OO) SEQ IDNo. 41: 5' TCCTTGCAGCCTAGCAGTTTATAGTTCTGAGATGGAAAGTTGAAG 3'; (PP) SEQ ID No. 42: 5' CTTTGACCCTAAGAATAAGCACTGTGTGTTTCAAGGTGACCTCCT 3';

2. The focused oligonucleotides microarray of claim 1wherein each oligonucleotide further comprises a 5'-amino linker

3. A solid substrate material comprising covalently attached thereto two or more of the oligonucleotides of claim 2.

4. The solid substrate of claim 3 further comprising one or more control oligonucleotide sequences.

5. A method for selecting a therapeutic agent for the treatment of glioblastoma comprising: exposing a human glioma cell culture to a candidate substance; measuring expression levels of a glioma-associated gene panel, wherein said glioma associated gene panel comprises 2 or more genes that are differentially expressed in a human glioma cell culture, said genes comprising: α-mannosidase 2A2 (MAN2A2) gene, ST6 (α-N-acetyl-neuraminyl- 2,3-β-galactosyl— 1,3)-N-acetylgalactosaminide α2,6-sialyltransferase 5 (ST6GALNAC5) gene, ST6 β-galactosamide α2,6-sialyltranferase 1 (ST6GAL1) gene, O-linked N-cetylglucosamine (GIcNAc) transferase (UDP- N-acetylglucosamine : polypeptide-N-cetylglucosaminyltransferase) (OGT), transcript variant 3 gene, UDP-GIcNAc; βl,3-N-cetylglucosaminyltransferase 6 (B3GNT6) gene, Protein O-fucosyltransferase 5 (POFUTl) gene, chitinase 3-like 1 (CHI3L1) gene, or ST3 β-galactoside α2,3-sialyltransferase 3 (ST3GAL3) gene; and selecting a candidate substance that provides one or more of the following: an expression level of MAN2A2gene, an ST6GALNAC5 gene, an ST6GAL1 gene, an OGT gene, an B3GNT6 gene, alone or in combination that is substantially the same as expression levels thereof by a non-glioma human brain cell culture; an expression level of POFUTl gene, an CHI3L1 gene, an ST3GAL3 gene, alone or in combination that is substantially the same as expression levels thereof by a non-glioma human brain cell culture, wherein an candidate substance is selected that provides substantially the same expression levels of the selected glioma associated gene, the non-glioma associated gene, or a both, for the treatment of glioblastoma.

6. The method of claim 5 wherein the culture of human glioma cells comprises a culture of human glioma cells of cell line SNB 19, D54MG, U87MG, U373MG, U l 18MG, U251 or A l 72.

7. The method of claim 5 further including monitoring the expression level of a control gene in the glioma human brain cell culture, wherein the control gene is glyceraldyhyde-3 -phosphate dehydrogenase (GAPDH).

8. The method of claim 5 wherein the glioma associated gene panel that represents an expression profile comprised of a set of genes that bind to a panel of 45-mer oligonucleotides having sequences of one or more of a first set of oligonucleotides (a), and one or more of a second set of 45-mer oligonucleotides set of oligonucleotides (b), said first set (a) comprising: (a) first set:

(A) SEQ ID No. 1: 5' CAAATATTCTGGGGTTGAGGGAAATTGCTGCTGTCTACAAAATGC 3'; (B) SEQ ID No. 2: 5' GAGCCAAACATCCTACAAGACACAGTGACCATACTAATTATACCC 3'; (C) SEQ IDNo. 3: 5' CCTGGCTTCTAGATCTGGAACCTTACCACGTTACTGCATACTGAT 3'; (D) SEQ IDNo. 4: 5' CGTTATCATTGGTCTGGTGAGATGTTTCATATTTGTGACAGTTAA 3'; (E) SEQ IDNo. 5: 5' CCAGATCAGTCAGAGCCCCTACAGCATTGTTAAGAAAGTATTTGA 3'; (F) SEQ ID No. 6: 5' TAGTGTATCATGTTTTCCCTGTTGGTATGTAGCCTGGATAAATGC 3'; (G) SEQ IDNo. 7: 5' TCCCTGTATAGAAATGTGGAATTGTCCCTTTGTAGCCAACTATAA 3'; (H) SEQ IDNo. 8: 5' CACTCCATATATTCAGCATCGTCAGAGAAACCCAAATCAGCCATT 3'; (I) SEQ IDNo. 9: 5' ATGCTAAGGAACACCACATGCCATTATTAACTTCACATTCTACAA 3'; (J) SEQ IDNo. 10: 5' CATCTACTTGGCAAGGTCATAGACAATTCCTCCAGAGACACTGAG 3'; (K) SEQ IDNo. 11: 5' TATGATCGGTTGGGCTTCCTCCTGAATCTGGACTCTAAACTCTCA 3'; (L) SEQ IDNo. 12: 5' AGACGCCTACAACAAGAAGCAGACCATTCACTACTATGAGCAGAT 3'; (M) SEQ IDNo. 13: 5' GGCTTCCCTGTAATCCTTTCTGCTCCTTGGTACTTAGATTTGATT 3'; (N) SEQ IDNo. 14: 5' GAGGCGGAAGTCTAGAGCTGCATGATCTGATAGGGTTTGTGACAG 3'; and, said second set (b) comprising (b) second set:

(O) SEQ IDNo. 15: 5' GGACCTCGTCTTTATGAAACACACACCTGGAATAAAACCACTTCT 3'; (P) SEQ IDNo. 16: 5' CAGCATAATGATTTGAGATTGGTCCATGTTGTGTGATTCAGTGGT 3'; (Q) SEQ IDNo. 17: 5' CTTTGTGAGCCGTGTCGTATGACCTAGTAAACTTTGTACCAATT 3'; (R) SEQ IDNo. 18: 5' AATCATCCAGTCATTCCAATGGCAAATAAGTTCTCACCTACCCTT 3'; (S) SEQ IDNo. 19: 5' AAGAAAGTGAAATGAGCCGACAGCCCAGGTGATAGAAATAAATTG 3'; (T) SEQ IDNo. 20: 5' CCCCATACCCTCACCCTTAAAATTCTCCTGTAACTCAACTAACAA 3'; (U) SEQ IDNo. 21: 5' GGTTCACCCACCTGGAGCTGGAATTATCACTTCCGAAATAAAGCG 3'; (V) SEQ ID No. 22: 5' CAGTTCTGAAGATTCACGTATCCATCTGGAGACCTACAGGAAGAA 3'; (W) SEQ IDNo. 23: 5' TAAAGAGTCAGACGCCACAGGCATTCCCATTAAAGTCAGAAACTA 3' (X) SEQ ID No. 24: 5' CTGGGCTGGGTATGTGCCTACCGATGACAATGTGTAAATAAATGC 3'; (Y) SEQ IDNo. 25: 5' GGTTTTATCTTGGCTTTTAGTAATCATGTTGGCTGGTCTGGTCAC 3'; (Z) SEQ IDNo. 26: 5' GTGACTGCCCCAGACTTGGTTTTGTAATGATTTGTACAGGAATAA 3'; (AA) SEQ IDNo. 27: 5' CTCAGTCCAGAGACCTAACATTCAGAATATAGCATTGGTTGCCTA 3'; (BB) SEQ ID No. 28: 5' TTTGAACAACTGACTCTTGATGGACACAACCTTCCTTCTCTCGTC 3'; (CC) SEQ ID No. 29: 5' TATGTGTGGCATCCATGTTGGTTTCGTCTGTCTGTAATGTGAATT 3'; (DD) SEQ IDNo. 30: 5' CCTCACGGCCGATGCTCTGCAGTCTGACAAGCTTCAGACCTGGAC 3'; (EE) SEQ IDNo. 31: 5' TGGTAATTTATCCTTCCTAACTCTTTAATCCTGAATGATGGTTGG 3'; (FF) SEQ ID No. 32: 5' GAGGACCTGACCCTACTCCCTTGCCCTAGATAGTTTATTATTATT 3'; (GG) SEQ IDNo. 33: 5' AATACCCACACTTACCTTAATACAAACATCCCAGCAACAGCACAT 3'; (HH) SEQ IDNo. 34: 5' CTCAGTCCAGAGACCTAACATTCAGAATATAGCATTGGTTGCCTA 3'; (II) SEQ IDNo. 35 5' CTGCCCTCCGCCATCCCTGCTATTTAAATTATTTAAGGTCTCTGG 3'; (JJ) SEQ IDNo. 36: 5' CTGAGGAGCAGCTGTTCTGATGCACGGGAACAAGCAGCACCTGCA 3'; (KK) SEQ IDNo. 37: 5' CTTATGGGAGCTGGCACGTCACCCACAGCCTGGCAGCTCTGATCA 3'; (LL) SEQ IDNo. 38: 5' AAAAGCTTATGGGAGCTGGCACGTCACAAAAAGAAAAAAACCAAG 3'; (MM) SEQ ID No. 39: 5' CGTTATCATTGGTCTGGTGAGATGTTTCATATTTGTGACAGTTAA 3'; (NN) SEQ ID No. 40: 5' ACAATGGAATCTTCCCTCTGTTCTCTGATAACCTACTTGCTTACT 3'; (OO) SEQ IDNo. 41: 5' TCCTTGCAGCCTAGCAGTTTATAGTTCTGAGATGGAAAGTTGAAG 3'; (PP) SEQ IDNo. 42: 5' CTTTGACCCTAAGAATAAGCACTGTGTGTTTCAAGGTGACCTCCT 3'; 9. The method of claim 5 wherein a selected therapeutic agent provides a glioma associated increase in expression of one or more non-glioma associated genes identified by binding to a 45-mer from having a sequence of: SEQ ID No. 20: 5' CCCCATACCCTCACCCTTAAAATTCTCCTGTAACTCAACTAACAA 3'; SEQ IDNo. 23: 5' TAAAGAGTCAGACGCCACAGGCATTCCCATTAAAGTCAGAAACTA 3'; SEQ ID No. 27 5' CTCAGTCCAGAGACCTAACATTCAGAATATAGCATTGGTTGCCTA 3'; SEQ IDNo. 31: 5' TGGTAATTTATCCTTCCTAACTCTTTAATCCTGAATGATGGTTGG 3'; SEQ ID No. 39: 5' CGTTATCATTGGTCTGGTGAGATGTTTCATATTTGTGACAGTTAA 3'; or any combination of SEQ ID No. 20, 23, 27, 31, and 39.

10. The method of claim 5 wherein a selected therapeutic agent provides a decrease in expression levels of one or more of a glioma associated gene identified by binding to a 45-mer having a sequence of:

SEQ ID No. 2: 5' GAGCCAAACATCCTACAAGACACAGTGACCATACTAATTATACCC 3'; SEQ ID No. 6: 5' TAGTGTATCATGTTTTCCCTGTTGGTATGTAGCCTGGATAAATGC 3'; SEQ IDNo. 11: 5' TATGATCGGTTGGGCTTCCTCCTGAATCTGGACTCTAAACTCTCA 3'; or any combination of SEQ ID No. 2, 6 and 11.

11. The method of claim 5 or 8 wherein the expression levels are determined by microarray analysis of mRNA transcripts.

12. The method of claim 5 or 8 wherein the expression levels are determined by multiplex PCR of transcripts.

13. The method of claim 5 or 8 wherein the oligonucleotides are disposed in the surface of a chip or wafer. 14. The method of claim 5 wherein microarray analysis comprises use of oligonucleotides that hybridize to transcripts or cDNAs for the selected genes.

15. A method for treating a patient having or at risk of having a glioma whose tumor demonstrates a decreased expression level of a MAN2A2 gene, a ST6GALNAC5 gene, a ST6GAL1 gene, a OGT gene, a B3GNT6 gene, or a combination thereof, or an increased expression level of POFUTl gene, CHI3L1 gene, ST3GAL3 gene, or an combination thereof, comprising the steps of: preparing a viral vector having a sequence comprising: (a) a MAN2A2 gene sequence, a ST6GALNAC5 gene sequence, a ST6GAL1 gene sequence, a OGT gene sequence, B3BNT6 gene sequence, or a combination thereof; (b) an antisense molecule that reduces the expression of the POFUTl gene, the CHI3L1 gene, the ST3GAL3 gene, or a combination of these antisense molecules thereto; or c) a combination of (a) and (b); and administering the viral vector to a patient having glioma.

16. The method of claim 15 wherein the viral vector is an adenoviral vector.

17. The method of claim 16 wherein the adenoviral vector is provided as viral particles.

18. The method of claim 15 wherein the glioma is a type 4 glioma.

19. A diagnostic kit comprising a solid or semisolid substrate comprising a panel of 2 or more oligonucleotides having a sequence of :

(A) SEQ ID No. 1: 5' CAAATATTCTGGGGTTGAGGGAAATTGCTGCTGTCTACAAAATGC 3'; (B) SEQ ID No. 2: 5' GAGCCAAACATCCTACAAGACACAGTGACCATACTAATTATACCC 3'; (C) SEQ IDNo. 3: 5' CCTGGCTTCTAGATCTGGAACCTTACCACGTTACTGCATACTGAT 3'; (D) SEQ ID No. 4: 5' CGTTATCATTGGTCTGGTGAGATGTTTCATATTTGTGACAGTTAA 3'; (E) SEQ IDNo. 5: 5' CCAGATCAGTCAGAGCCCCTACAGCATTGTTAAGAAAGTATTTGA 3'; (F) SEQ ID No. 6: 5' TAGTGTATCATGTTTTCCCTGTTGGTATGTAGCCTGGATAAATGC 3'; (G) SEQ IDNo. 7: 5' TCCCTGTATAGAAATGTGGAATTGTCCCTTTGTAGCCAACTATAA 3'; (H) SEQ IDNo. 8: 5' CACTCCATATATTCAGCATCGTCAGAGAAACCCAAATCAGCCATT 3'; (I) SEQ IDNo. 9: 5' ATGCTAAGGAACACCACATGCCATTATTAACTTCACATTCTACAA 3'; (J) SEQ IDNo. 10: 5' CATCTACTTGGCAAGGTCATAGACAATTCCTCCAGAGACACTGAG 3'; (K) SEQ IDNo. 11: 5' TATGATCGGTTGGGCTTCCTCCTGAATCTGGACTCTAAACTCTCA 3'; (L) SEQ IDNo. 12: 5' AGACGCCTACAACAAGAAGCAGACCATTCACTACTATGAGCAGAT 3'; (M) SEQ IDNo. 13: 5' GGCTTCCCTGTAATCCTTTCTGCTCCTTGGTACTTAGATTTGATT 3'; (N) SEQ IDNo. 14: 5' GAGGCGGAAGTCTAGAGCTGCATGATCTGATAGGGTTTGTGACAG 3'; (O) SEQ IDNo. 15: 5' GGACCTCGTCTTTATGAAACACACACCTGGAATAAAACCACTTCT 3'; (P) SEQ IDNo. 16: 5' CAGCATAATGATTTGAGATTGGTCCATGTTGTGTGATTCAGTGGT 3'; (Q) SEQ IDNo. 17: 5' CTTTGTGAGCCGTGTCGTATGACCTAGTAAACTTTGTACCAATTC 3'; (R) SEQ IDNo. 18: 5' AATCATCCAGTCATTCCAATGGCAAATAAGTTCTCACCTACCCTT 3'; (S) SEQ IDNo. 19: 5' AAGAAAGTGAAATGAGCCGACAGCCCAGGTGATAGAAATAAATTG 3'; (T) SEQ ID No. 20: 5' CCCCATACCCTCACCCTTAAAATTCTCCTGTAACTCAACTAACAA 3'; (U) SEQ IDNo. 21: 5' GGTTCACCCACCTGGAGCTGGAATTATCACTTCCGAAATAAAGCG 3'; (V) SEQ IDNo. 22: 5' CAGTTCTGAAGATTCACGTATCCATCTGGAGACCTACAGGAAGAA 3'; (W) SEQ IDNo. 23: 5' TAAAGAGTCAGACGCCACAGGCATTCCCATTAAAGTCAGAAACTA 3'; (X) SEQ IDNo. 24: 5' CTGGGCTGGGTATGTGCCTACCGATGACAATGTGTAAATAAATGC 3'; (Y) SEQ IDNo. 25: 5' GGTTTTATCTTGGCTTTTAGTAATCATGTTGGCTGGTCTGGTCAC 3'; (Z) SEQ ID No. 26: 5' GTGACTGCCCCAGACTTGGTTTTGTAATGATTTGTACAGGAATAA 3'; (AA) SEQ IDNo. 27: 5' CTCAGTCCAGAGACCTAACATTCAGAATATAGCATTGGTTGCCTA 3'; (BB) SEQ ID No. 28: 5' TTTGAACAACTGACTCTTGATGGACACAACCTTCCTTCTCTCGTC 3'; (CC) SEQ ID No. 29: 5' TATGTGTGGCATCCATGTTGGTTTCGTCTGTCTGTAATGTGAATT 3'; (DD) SEQ IDNo. 30: 5' CCTCACGGCCGATGCTCTGCAGTCTGACAAGCTTCAGACCTGGAC 3'; (EE) SEQ IDNo. 31: 5' TGGTAATTTATCCTTCCTAACTCTTTAATCCTGAATGATGGTTGG 3'; (FF) SEQ ID No. 32: 5' GAGGACCTGACCCTACTCCCTTGCCCTAGATAGTTTATTATTATT 3'; (GG) SEQ IDNo. 33: 5' AATACCCACACTTACCTTAATACAAACATCCCAGCAACAGCACAT 3'; (HH) SEQ ID No. 34: 5' CTCAGTCCAGAGACCTAACATTCAGAATATAGCATTGGTTGCCTA 3'; (II) SEQ IDNo. 35: 5' CTGCCCTCCGCCATCCCTGCTATTTAAATTATTTAAGGTCTCTGG 3'; (JJ) SEQ IDNo. 36: 5' CTGAGGAGCAGCTGTTCTGATGCACGGGAACAAGCAGCACCTGCA 3'; (KK) SEQ IDNo. 37: 5' CTTATGGGAGCTGGCACGTCACCCACAGCCTGGCAGCTCTGATCA 3'; (LL) SEQ IDNo. 38: 5' AAAAGCTTATGGGAGCTGGCACGTCACAAAAAGAAAAAAACCAAG 3'; (MM) SEQ ID No. 39: 5' CGTTATCATTGGTCTGGTGAGATGTTTCATATTTGTGACAGTTAA 3'; (NN) SEQ ID No. 40: 5' ACAATGGAATCTTCCCTCTGTTCTCTGATAACCTACTTGCTTACT 3'; (OO) SEQ IDNo. 41: 5' TCCTTGCAGCCTAGCAGTTTATAGTTCTGAGATGGAAAGTTGAAG 3'; (PP) SEQ ID No. 42: 5' CTTTGACCCTAAGAATAAGCACTGTGTGTTTCAAGGTGACCTCCT 3';

20. A diagnostic kit comprising a solid or semi-solid substrate having disposed thereon a panel of 2 or more oligonucleotides having a sequence of: SEQ ID No. 2: 5' GAGCCAAACATCCTACAAGACACAGTGACCATACTAATTATACCC 3'; SEQ ID No. 6: 5' TAGTGTATCATGTTTTCCCTGTTGGTATGTAGCCTGGATAAATGC 3'; SEQ IDNo. 11: 5' TATGATCGGTTGGGCTTCCTCCTGAATCTGGACTCTAAACTCTCA 3'; SEQ IDNo. 20: 5' CCCCATACCCTCACCCTTAAAATTCTCCTGTAACTCAACTAACAA 3'; SEQ IDNo. 23: 5' TAAAGAGTCAGACGCCACAGGCATTCCCATTAAAGTCAGAAACTA 3'; SEQ IDNo. 27: 5' CTCAGTCCAGAGACCTAACATTCAGAATATAGCATTGGTTGCCTA 3'; SEQ IDNo. 31: 5' TGGTAATTTATCCTTCCTAACTCTTTAATCCTGAATGATGGTTGG 3'; SEQ ID No. 39: 5' CGTTATCATTGGTCTGGTGAGATGTTTCATATTTGTGACAGTTAA 3';

2 1. The kit of claim 19 or 20 wherein the solid or semi-solid substrate comprises a microchip.

22. The kit of claim 19 or 20 wherein the solid or semi-solid substrate further comprises a control oligonucleotide sequence.

23. The kit of claim 19 or 20 wherein the oligonucleotides further comprise a 5'- amino linker.