Gene expression profiling of low-grade diffuse astrocytomas by cDNA arrays

Diffuse astrocytoma WHO grade II is a well-differentiated, slowly growing t umor that has an inherent tendency to progress to anaplastic astrocytoma (W HO grade III) and, eventually, to glioblastoma (WHO grade IV). Little is kn own about its molecular basis, except for p53 mutations that are found in > 60% of cases. In a search for additional genetic alterations, we carried ou t gene expression profiling of 11 diffuse astrocytomas using cDNA expressio n arrays, Expression of six genes (TIMP3, c-myc, EGFR, DR-nm23, nm23-H4, an d GDNPF) was detected in 64-100% of diffuse astrocytomas, but not in nontum orous brain tissue, Seven genes (AAD14, SPARC, LRP, PDGFR-alpha, 60S riboso mal protein L5, PTN, and hBAP) were found to be up-regulated more than 2-fo ld in 20-60% of cases, whereas 11 genes (IFI 9-27, protein kinase CLK, TDGF 1, B1N1, GAB1, TYRO3, LDH-A, adducin 3, GUK1, CDC10, and KRT8) were down-re gulated to less than 50% of normal levels in 64-100% of cases. Semiquantita tive conventional reverse transcription-PCR was performed for 11 genes, 9 o f which showed an expression profile similar to that obtained with cDNA exp ression arrays. Immunohistochemical staining for SPARC showed:cytoplasmic i mmunoreactivity of neoplastic cells in all diffuse astrocytomas analyzed. T hese results indicate significant changes in gene expression in diffuse ast rocytomas, but it remains to be shown which Of these are causally related t o the transformation of glial cells.