Genetic deletions to chromosome 10 have been extensively documented for human glioblastomas (GBMs). To identify gene products that may be involved in malignant progression, a subtractive hybridization was performed between GBM cells and hybrid cells suppressed for tumorigenicity following microcell transfer of chromosome 10. One novel cDNA isolated from this subtraction showed consistent upregulation (approximately 4 to 10-fold) that correlated with the nontumorigenic phenotype of the hybrid cells. Subsequent analysis resulted in the identification of a full length cDNA (2,569 bp) termed RIG (regulated in glioma). RIG expression was either not detected or detected only at low levels in cultured glioma cells and primary glioblastoma specimens compared to normal brain cells. The 2.6 kb RIG mRNA was expressed predominantly in normal brain with lower levels in heart and lung. Sequence analysis showed no significant homology to known gene products. Genomic alterations of RIG were present in approximately 25% of glioma cell lines examined. Also, RIG mapped to chromosome 11p15.1, a region that is known to be altered in malignant astrocytomas. The differential expression pattern, tissue distribution and chromosomal location of RIG suggests it serves as a molecular marker for or may play a role in the malignant progression of GBMs.