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Meningiomas add up to 25% of intracranial tumors. Although the majority is considered histologically benign, the prediction of their potential aggressiveness is still unclear. We studied the histopathology and aberrations of chromosomes 1p, 14, and 22 by FISH (fluorescence in situ hybridization) in histologically benign meningiomas of 70 patients for the purpose of defining the prognostic value of these alterations in tumoral progression and the risk of recurrence. According to the WHO histopathological criteria, the study set comprised 53 benign, 11 atypical, and 6 anaplastic meningiomas. In benign meningiomas, 25% of the cases displayed a normal karyotype, isolated monosomy 22 (36%), monosomy 22 + 1p deletion (14%), 1p deletion (10%), monosomy 22 + 14q deletion (5%), monosomy 22 + 1p deletion + 14q deletion (5%), or other alterations (5%). Grade II meningiomas presented losses in chromosome 14 in most of the cases (67%), and Grade III meningiomas showed alterations in chromosome 14 in all patients. We observed an overall relapse rate of 31%: recurrence was observed in 19% of Grade I meningiomas, 64% of Grade II, and 83% of Grade III. 9 out of 10 recurrent cases revealed abnormalities in chromosomes 1 and 14, which was a notably higher incidence compared to the series of tumors without relapse. Thus, benign meningiomas with cytogenetic alterations in chromosomes 1p and 14 may be more closely related to atypical meningiomas than benign meningiomas without these alterations, especially in terms of recurrence risk.

Glioblastoma multiforme is the most common and most aggressive of the primary brain tumors. The mean survival of patients is 10-12 months. Conventional therapy of surgery, radiation and chemotherapy is largely palliative. Cytogenetically, karyotypes of glioblastomas are very complex with trisomy 7 and monosomy 10 as the most frequent abnormalities. A genetic alteration that is significantly more frequent in primary than in secondary glioblastomas, the latter arising from preceding low-grade gliomas, is epidermal growth factor receptor gene (EGFR) amplification, whereas TP-53 mutations are significantly more frequent in low-grade gliomas and secondary glioblastomas derived there- from. We report the histological and genetic study of two glioblastomas, one case arising de novo and the other case arising 3 years after a previously diagnosed anaplastic astrocytoma, with concurrent EGFR amplification and TP-53 mutation. These anomalies were initially deemed as mutually exclusive. However, a small percentage of cases have been found with both anomalies although at a significantly lower level than could be expected. We have analyzed these two cases cytogenetically and by molecular studies in order to detect additional alterations associated with this phenotype. Cytogenetically, both cases showed in common the monosomy of chromosomes 10 and 17. At the molecular level, a rare mutation of TP-53 was found in the secondary glioblastoma and hypermethylation of the promoter region of p16(INK4a) and p14(ARF) genes were observed in the primary and secondary glioblastoma, respectively.

Glioblastoma is the most common primary tumor of the central nervous system, but the underlying genetic changes that give rise to these tumors are still poorly understood. We report a primary glioblastoma with an unusual age of presentation. The patient was a 22-year-old man with a survival of 16 months. Morphological findings showed an increase of cellularity with positive GFAP and EGFR expression, increase of proliferate index, vascular hyperplasia with glomeruloid structures and necrosis. Molecular analysis showed EGFR amplification. No mutations of the TP53 or amplification of MDM2 and CDK4 were detected. Neither homozygous deletion of the 9p21 locus genes nor aberrant methylation were found. The cytogenetic study showed a clonal karyotype. The metaphases presented, among other anomalies, a small ring chromosome and double-minutes chromosomes. Using FISH and CGH techniques, it was found that the ring chromosome was a partial trisomy of chromosome 7, and the region implicated corresponded to 7p13-q21. Partial trisomies in glioblastoma could play an important role in defining those regions where genes implicated in this tumor process may be found. We studied the possible correlation of these findings with the tumoral phenotype.

Glioblastoma multiforme (GBM) is characterized by intratumoral heterogeneity in both histomorphological and genetic changes, displaying a wide variety of numerical chromosome aberrations, the most common of which are trisomy 7 and monosomy 10. The amplification of the epidermal growth factor receptor (EGFR) gene is the most frequently reported genetic abnormality. The associations between these parameters and their implication in the tumoral progression are poorly understood. We performed simultaneous fluorescence in situ hybridization (FISH) with centromeric DNA probes for chromosomes 7 and 10 in smear preparations, and EGFR gene amplification by PCR from 25 cases of GBM. Trisomy/ polysomy for chromosome 7 was present in 76% of cases and monosomy 10 in 68%. Both alterations were associated in 56% of cases. The EGFR gene was amplified in 52% of tumors; in 44% associated with trisomy/ polysomy 7, and in 36% with monosomy 10. The three parameters were associated together in 28% of cases. Kaplan-Meier survival rate analysis demonstrated lower survival rates in patients with monosomy 10, trisomy 7, and monosomy associated with trisomy 7. The other combinations were not different in frequency in relation to survival. In the present study, trisomy/polysomy 7 and monosomy 10 have been found to be frequently associated. The combination of both anomalies is probably important in the tumorigenesis of glioblastoma. Moreover, this association is apparently independent of EGFR gene amplification, which could be a later event in this process.

The cytogenetic findings, based on G-banding, in six meningiomas are reported. Normal karyotypes were found in three cases and monosomy of chromosome 22 in the remaining three. In one of these three cases, a malignant meningioma, several chromosomes were lost, gonosome Y included. The possible significance of the association of chromosome alterations in meningiomas with the histology of the tumor and its biological aggressivity is discussed.