DIFFERENTIALLY EXPRESSED GENE-PRODUCTS IN GLIOBLASTOMA CELLS SUPPRESSED FOR TUMORIGENICITY

The loss of large segments or an entire copy of chromosome 10 is the m ost common genetic alteration in human glioblastomas. To address the b iological and molecular consequences of this chromosomal alteration, w e transferred a human chromosome 10 into a glioma cell clone devoid of an intact copy, The hybrid cells exhibited an altered cellular morpho logy, a decreased saturation density, and a suppression of both anchor age-independent growth and tumor formation in nude mice. The hybrids a lso expressed the recently identified candidate tumor suppressor gene MMAC1/PTEN, To further identify gene products that may be involved in glioma progression, a subtractive hybridization was performed between the human glioblastoma cells and the phenotypically suppressed hybrid cells to identify differentially expressed gene products. Sixty-one cl ones were identified, with nine clones being preferentially expressed in the hybrid cells. Four cDNA clones represented markers of different iation in glial cells. Two cDNA clones shared homology with platelet d erived growth factor-alpha, and the insulin receptor, respectively, bo th genes previously implicated in glioma progression. A novel gene pro duct that was expressed predominantly in the brain, hut which did not map to chromosome 10, was also identified. This clone contained an ele ment that was also present in three additional clones, two of which al so exhibited differential expression, Consequently, the presence of a functional copy of chromosome 10 in the glioma cells results in differ ential expression of a number of gene products, including novel genes as well as those associated with glial cell differentiation.