MPTH-28STUDY OF THE ROLE OF IFI-16 EXPRESSION IN GLIOMAS

Abstract

Interferon inducible protein 16 (IFI-16) is a member of the p200 human family proteins, having two domains: C-terminus binding dsDNA and N-terminus as a typical protein-protein interaction domain. IFI-16 gene is located at 1q23.1 chromosome, its functions ranging from transcriptional regulation, apoptosis, proliferation and differentiation. IFI-16 is mostly expressed in epithelial, endothelial and hematopoietic tissues, with nuclear localization signal: in the nucleolus it is able to activate and fine-tune the transcription, when in the nucleoplasm probably it is inactivated. In the nucleoli a physical and functional link of IFI-16 to p53 has been reported, as negative regulator of the cell cycle. We have studied IFI-16 expression in 40 low grade and 40 anaplastic gliomas (half of them analysed with their relapse) and 40 glioblastomas using immunohistochemical and molecular techniques, using two antibodies against the C- and N-terminus of IFI-16. Nuclear accumulation of p53, IDH1(R132H), MGMT methylation status and LOH of chromosomes 1p, 19q, 9p, 17p and 10q were also evaluated. We mainly found a nucleolar expression of IFI-16 in astrocytic lower grade gliomas, related to p53: this physical and functional binding was also demonstrated by co-immunoprecipitation and Protein Ligation Assay analysis. In anaplastic gliomas and glioblastomas, IFI-16 is largely expressed in the nucleoplasm, unrelated to p53 expression. This shift of localization suggests a possible loss of its role as protective factor in lower grade astrocytic gliomas. In oligodendrogliomas IFI-16 expression was completely absent and it is strictly related to 1p/19q co-deletion. Our results, related to clinical data, identify IFI-16 as a possible prognostic marker in glioma patients and of interest to define new molecular profiles for their therapy. This is the first study of IFI-16 in gliomas, suggesting an early role of this molecule in proliferation and malignant progression of these tumours.