Altered glycosylation has been linked to cancer cell metastasis and invasivity. We have previously shown that expressing a specific sialyltransferase gene in gliomas inhibited tumor formation, in vivo. In order to identify other ''glyco-gene'' targets with therapeutic potential, focused 45-mer oligonucleotide microarrays were constructed containing all of the cloned human glyco-genes. Gene expression profiles of normal human brain and malignant gliomas were compared and microarray datasets analyzed using significance analysis of microarrays algorithms. There were 11 genes more highly expressed in gliomas compared to normal brain and 25 genes more highly expressed in normal brain compared to gliomas. Among the most noteworthy were high levels of MAN2A2 and ST6GalNAcV in normal brain tissue and high levels of POFUT1 and CHI3L1 in the gliomas, all changes corroborated by qRT-PCR. Historically, identification of changes in tumorassociated glycoconjugate expression was obtained by measuring individual enzyme activities or structural changes of specific molecules. With microarray technology, it is possible to measure all of genes associated with glycoconjugate biosynthesis and degradation simultaneously. Our data demonstrate that there are many significant and novel differences in glyco-gene expression that represent potential targets for the development of therapeutics for the treatment of brain tumors. Virtually all tumor cells display aberrant cell-surface glycosylation patterns. These are most often caused by alterations in the biosynthesis and degradation of the oligosaccharide chains found in the glycoproteins, glycosphingolipids, proteoglycans, and glycosaminoglycans that comprise the cellsurface glycoconjugates associated with adhesion and migration in normal cellular function and metastasis and invasivity in tumor cells (Hakomori 2002).There are many reports of aberrant cell-surface glycoconjugate expression in brain tumors. These include altered ganglioside expression (Traylor and Hogan 1980;Fredman et al. 1986;Jennemann et al. 1990Jennemann et al. , 1994Wikstrand et al. 1991;Shinoura et al. 1992;Chang et al. 1997;Comas et al. 1999;Hamasaki et al. 1999;Markowska-Woyciechowska et al. 2000;Pan et al. 2000;Popko et al. 2002;Mennel and Lell 2005), tumor cell-associated ganglioside shedding (Ladisch et al. 1987Nakamura et al. 1991;Li et al. 1996), b1-integrins, and N-CAM (Paulus et al. 1996;Gratsa et al. 1997). For recent reviews, see Fredman et al. (2003), Fish (1996), Pilkington (1992, Yates (1988) and Mikkelsen et al. (1998). The first report implicating aberrant glycosyltransferase gene expression in human brain tumors was a survey of a2,6ST mRNA expression in panel of astrocytic, meningeal, and metastatic primary human brain tumors by Kaneko et al. (1996). No a2,6ST mRNA expression was found in the astrocytic or metastatic tumors but robust expression in meningeal tumors was observed. This was followed by a report by Yamamoto et al. (1997b) showing that a2,3ST mRNA and a2,3-linked glycoprotein sialyl...