ANALYSIS OF THE PTEN GENE IN HUMAN MENINGIOMAS

Previous observations demonstrated that the neurofibromatosis type 2 g ene (NF2) plays an important role in the pathogenesis of the transitio nal, fibroblastic and malignant variants of human meningiomas. No spec ific genes have been associated with the pathogenesis of meningothelia l meningiomas and with the progression to anaplastic meningiomas. Howe ver, allelic losses on chromosomal arms 1p, 10q and 14q have been impl icated in the process of malignant progression. Recently, PTEN (phosph atase and tensin homolog deleted on chromosome ten) also termed MMAC1 (mutated in multiple advanced cancers 1) or TEP1 (TGF-regulated and ep ithelial cell-enriched phosphatase), emerged as a candidate gene on ch romosome 10q23.3. Initial studies revealed mutations of PTEN in limite d series of glioblastomas, breast, kidney and prostate carcinomas main ly as cell lines. In order to evaluate the involvement of PTEN in the development of meningiomas, we have analysed the entire coding sequenc e of the gene in a series of 55 meningiomas (WHO grade I), 10 atypical meningiomas (WHO grade II) and 10 anaplastic meningiomas (WHO grade I II). No PTEN mutations were seen in the WHO grade I meningiomas. Howev er, one of the anaplastic meningiomas carried a somatic mutation. In a ddition, all tumours were examined for the presence of homozygous dele tions of PTEN but these were not detected in any of the meningiomas, O ur data suggest that mutations in PTEN are not involved in the formati on of low grade meningiomas, but may contribute to malignant progressi on in a fraction of anaplastic meningiomas.