Mutations in the neurofibromatosis 2 (NF2) gene are the predominant cause in the development of sporadic schwannomas and are also involved in the pathogenesis of meningiomas and ependymomas.
Reverse transcription-polymerase chain reaction followed by agarose gel electrophoresis, single strand conformation polymorphism analysis, and automated deoxyribonucleic acid sequence analysis were used to screen for mutations in the NF2 gene transcript in seven unrelated patients with sporadic intramedullary spinal cord ependymomas.
Alleotyping showed loss of heterozygosity (LOH) involving the wild-type alleles in seven tumors in the family including the ependymoma, which is the first MEN1-related case that shows genetic abnormality in chromosome 11q13, suggesting that MEN1 gene might be involved in the tumorigenesis of a subset of ependymomas.
All tumors showed staining with an antibody to a C-terminal peptide of neurofibromin, confirming that full-length neurofibromin is present in these vestibular schwannomas, meningiomas, and ependymomas.
The VEGF receptors, kinase domain region (KDR) and Fms-like-tyrosine kinase (Flt-1), also were upregulated in the tumor vasculature of glioblastoma multiforme, anaplastic oligodendrogliomas, and ependymomas with necrosis, whereas the astrocytomas grade II, anaplastic astrocytomas, and oligodendroglioma tumors tended to express a weak to nondetectable signal.
The VEGF receptors, kinase domain region (KDR) and Fms-like-tyrosine kinase (Flt-1), also were upregulated in the tumor vasculature of glioblastoma multiforme, anaplastic oligodendrogliomas, and ependymomas with necrosis, whereas the astrocytomas grade II, anaplastic astrocytomas, and oligodendroglioma tumors tended to express a weak to nondetectable signal.
From an earlier study in a family in which four cousins developed an ependymoma, we concluded that an ependymoma-susceptibility gene, which is not the NF2 gene in 22q12, might be located on chromosome 22.
These findings suggest that a considerable fraction of spinal ependymomas are associated with molecular events involving chromosome 22 and that mutations in the NF2 gene may be of primary importance for their genesis.
We investigated 47 glioblastomas (GBM), 14 anaplastic astrocytomas (AA), 6 non-pilocytic low-grade astrocytomas (LGA), 21 low-grade and anaplastic oligodendrogliomas (O) and oligoastrocytomas (OA), and 3 ependymomas (E) for mutation of the PTEN gene using denaturing gradient gel electrophoresis (DGGE) followed by DNA sequencing.
High frequency of allelic deletions was detected at marker D10S215 (80%) at the proximal 10q23 region in both oligodendroglial and ependymal tumours and between markers D10S216 (42%) and D10S169 (67%) at distal 10q25-26 region in oligodendroglial tumours.No mutations of PTEN/MMAC1 were found. p53 mutations were detected in three oligoastrocytomas and one ependymoma; three out of five mutations were found in exon 4.
These observations suggest tissular or tumoral differences in the control of p73 gene transcription and alternative splicing, and raise the problem of the role of p73 isoforms in the control of tumor growth, particularly in ependymomas.
These observations suggest tissular or tumoral differences in the control of p73 gene transcription and alternative splicing, and raise the problem of the role of p73 isoforms in the control of tumor growth, particularly in ependymomas.
A tumor-suppressor gene, independent of the NF2 gene, which seems to be exclusively involved in intramedullary spinal cord ependymomas, might be implicated in the genesis of these intracranial tumors.
These results suggest that the amplification and/or overexpression of mdm2 may be one of the major molecular events occurring in the tumorigenesis of ependymomas.
Finally, ligand blotting and chemical-linking experiments revealed the presence of a approximately 100 kDa putative TTR receptor on the ependymoma cell membrane.
These results, in conjunction with data in the literature, suggest that the most frequently recurrent genomic loss in ependymomas does not involve the proximal 22q11.2 chromosome region but is localized distally to the hSNF5/INI1 locus.