Downregulation of putative tumor suppressor gene TSC-22 in human brain tumors.

BACKGROUND AND OBJECTIVES Our objective was to identify differentially expressed genes involved in the pathogenesis of glioblastoma multiforme (GBM). METHODS Screening of arrayed human fetal brain and human postnatal brain cDNA libraries was performed by differential hybridization with glioblastoma multiforme and human normal brain cDNAs. RESULTS Repeated differential hybridization of more than 100 cDNA clones selected by primary screening and analysis of RNA from adult normal brain and glial tumors showed 16 nucleotide sequences differentially expressed between normal brain and brain tumors. Among others, decreased content in astrocytic tumors was determined for TSC-22 mRNA corresponding to cDNA in the ICRFp507J1041 clone from human fetal brain cDNA library. Northern blot hybridization of RNA from different human brain tumors showed very low amounts of TSC-22 mRNA in most investigated samples of GBM, anaplastic astrocytoma, and some other tumors. Complete lack of expression of TSC-22 occurred in one sample of anaplastic astrocytoma, as well as in meningioma, brain sarcoma, sarcomatous meningioma, and oligodendroglioma. The differential expression of TSC-22 gene was confirmed by semiquantitative RT-PCR in 15 samples of astrocytomas WHO grade II-IV and three samples of normal brain. CONCLUSIONS Significantly decreased levels of TSC-22 mRNA in human brain and salivary gland tumors and antiproliferative role of TSC-22 strongly suggest a tumor suppressor role for TSC-22. J.