Dataset Information

Analysis of genomic alterations in benign, atypical, and anaplastic meningiomas: toward a genetic model of meningioma progression.

ABSTRACT: Nineteen benign [World Health Organization (WHO) grade I; MI], 21 atypical (WHO grade II; MII), and 19 anaplastic (WHO grade III; MIII) sporadic meningiomas were screened for chromosomal imbalances by comparative genomic hybridization (CGH). These data were supplemented by molecular genetic analyses of selected chromosomal regions and genes. With increasing malignancy grade, a marked accumulation of genomic aberrations was observed; i.e., the numbers (mean +/- SEM) of total alterations detected per tumor were 2.9 +/- 0.7 for MI, 9.2 +/- 1.2 for MII, and 13.3 +/- 1.9 for MIII. The most frequent alteration detected in MI was loss on 22q (58%). In MII, aberrations most commonly identified were losses on 1p (76%), 22q (71%), 14q (43%), 18q (43%), 10 (38%), and 6q (33%), as well as gains on 20q (48%), 12q (43%), 15q (43%), 1q (33%), 9q (33%), and 17q (33%). In MIII, most of these alterations were found at similar frequencies. However, an increase in losses on 6q (53%), 10 (68%), and 14q (63%) was observed. In addition, 32% of MIII demonstrated loss on 9p. Homozygous deletions in the CDKN2A gene at 9p21 were found in 4 of 16 MIII (25%). Highly amplified DNA sequences were mapped to 12q13-q15 by CGH in 1 MII. Southern blot analysis of this tumor revealed amplification of CDK4 and MDM2. By CGH, DNA sequences from 17q were found to be amplified in 1 MII and 8 MIII, involving 17q23 in all cases. Despite the high frequency of chromosomal aberrations in the MII and MIII investigated, none of these tumors showed mutations in exons 5-8 of the TP53 gene. On the basis of the most common aberrations identified in the various malignancy grades, a model for the genomic alterations associated with meningioma progression is proposed.

SUBMITTER: Weber RG

PROVIDER: S-EPMC25103 | biostudies-literature | 1997 Dec

REPOSITORIES: biostudies-literature

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Analysis of genomic alterations in benign, atypical, and anaplastic meningiomas: toward a genetic model of meningioma progression.

Weber R G RG Boström J J Wolter M M Baudis M M Collins V P VP Reifenberger G G Lichter P P

Proceedings of the National Academy of Sciences of the United States of America 19971201 26

Nineteen benign [World Health Organization (WHO) grade I; MI], 21 atypical (WHO grade II; MII), and 19 anaplastic (WHO grade III; MIII) sporadic meningiomas were screened for chromosomal imbalances by comparative genomic hybridization (CGH). These data were supplemented by molecular genetic analyses of selected chromosomal regions and genes. With increasing malignancy grade, a marked accumulation of genomic aberrations was observed; i.e., the numbers (mean +/- SEM) of total alterations detected ...[more]

PMID: 9405679

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Project description:BACKGROUND:Clinical behaviour of atypical meningiomas is not uniform. While, as a group, they exhibit a high recurrence rate, some pursue a more benign course, whereas others progress early. We aim to investigate the imaging and pathological factors that predict risk of early tumour progression and to determine whether early progression is related to outcome. METHODS:Adult patients with WHO grade II meningioma treated in three regional referral centres between 2007 and 2014 were included. MRI and pathology characteristics were assessed. Gross total resection (GTR) was defined as Simpson 1-3. Recurrence was classified into early and late (??24 vs. >?24 months). RESULTS:Among the 220 cases, 37 (16.8%) patients progressed within 24 months of operation. Independent predictors of early progression were subtotal resection (STR) (p?=?0.005), parafalcine/parasagittal location (p?=?0.015), peritumoural oedema (p?=?0.027) and mitotic index (MI)?>?7 (p?=?0.007). Adjuvant radiotherapy was negatively associated with early recurrence (p?=?0.046). Thirty-two per cent of patients with residual tumour and 26% after GTR received adjuvant radiotherapy. There was a significantly lower proportion of favourable outcomes at last follow-up (mRS 0-1) in patients with early recurrence (p?=?0.001). CONCLUSIONS:Atypical meningiomas are a heterogeneous group of tumours with 16.8% patients having recurrence within 24 months of surgery. Residual tumour, parafalcine/parasagittal location, peritumoural oedema and a MI?>?7 were all independently associated with early recurrence. As administration of adjuvant radiotherapy was not protocolised in this cohort, any conclusions about benefits of irradiation of WHO grade II meningiomas should be viewed with caution. Patients with early recurrence had worse neurological outcome. While histological and imaging characteristics provide some prognostic value, further molecular characterisation of atypical meningiomas is warranted to aid clinical decision making.

Dataset Information

Analysis of genomic alterations in benign, atypical, and anaplastic meningiomas: toward a genetic model of meningioma progression.

Publications

Analysis of genomic alterations in benign, atypical, and anaplastic meningiomas: toward a genetic model of meningioma progression.

Similar Datasets

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