Tumor initiating cells (TICs) provide a new paradigm for developing original therapeutic strategies.

Here, we screened for TICs in 47 human adult brain malignant tumors. Cells forming floating spheres in culture, and endowed with all of the features expected from tumor cells with stem−like properties were obtained from glioblastomas, medulloblastoma but not oligodendrogliomas.

A long−term self−renewal capacity was particularly observed for cells of malignant glio−neuronal tumors (MGNTs). Cell sorting, karyotyping and proteomic analysis demonstrated cell stability throughout prolonged passaging. Xenografts of fewer than 500 cells in nude mouse brain induced a progressively growing tumor. CD133, CD15/LeX/Ssea−1, CD34 expressions, or exclusion of Hoechst dye occurred in subsets of cells forming spheres, but did not indicate their capacity to form secondary spheres or tumors or resist to high doses of temozolomide.

Our results further substantiate the specificity of a subset of high grade gliomas, MGNT. TICs derived from these tumors represent a new tool to screen for innovative therapies.

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