Metabolic Aggressiveness in Benign Meningiomas with Chromosomal Instabilities

Abstract

Meningiomas are often considered benign tumors curable by surgery, but most recurrent meningiomas correspond to histologic benign tumors. Because alterations in chromosome 14 among others have suggested clinical aggressiveness and recurrence, determining both the molecular phenotype and the genetic profile may help distinguish tumors with aggressive metabolism. The aim of this study was to achieve higher specificity in the detection of meningioma subgroups by measuring chromosomal instabilities by fluorescence in situ hybridization and cytogenetics and metabolic phenotypes by high-resolution magic angle spinning spectroscopy. We studied 46 meningioma biopsies with these methodologies. Of these, 34 were of WHO grade 1 and 12 were of WHO grade 2. Genetic analysis showed a subgroup of histologic benign meningioma with chromosomal instabilities. The metabolic phenotype of this subgroup indicated an aggressive metabolism resembling that observed for atypical meningioma. According to the metabolic profiles, these tumors had increased energy demand, higher hypoxic conditions, increased membrane turnover and cell proliferation, and possibly increased resistance to apoptosis. Taken together, our results identify distinct metabolic phenotypes for otherwise benign meningiomas based on cytogenetic studies and global metabolic profiles of intact tumors. Measuring the metabolic phenotype of meningioma intact biopsies at the same time as histopathologic analysis may allow the early detection of clinically aggressive tumors. Cancer Res; 70(21); 8426-34. ©2010 AACR.

Gene Expression Profiles of Metabolic Aggressiveness and Tumor Recurrence in Benign Meningioma

“…All 54 meningioma samples studied here were classified into WHO meningioma grades I (40 cases) and grade II (14 cases) according to histopathological evaluation. Combined metabolic profiling, cytogenetics and FISH data for 34 of these meningiomas was previously reported [9] Patients were followed up for evaluating recurrence after surgery. Karyotyping was obtained in 37 cell cultures from 54 different cases.…”

“…These groups have been reported to have different metabolic behavior (benignA and benignB meninigioma [9]). According to these studies, classification of tumors in the benignB subgroup required the existence of chromosomal abnormalities detected either by FISH or by cytogenetics and/or levels of three out of four of the most representative metabolites (choline, lactate, taurine and fatty acids) within 2 standard deviations of the values for atypical meningioma reported.…”

“…Metabolic profiles were measured in 54 meningioma samples using Nuclear Magnetic Resonance (NMR) spectroscopy as described elsewhere [9]. In summary, the tissue sample for NMR spectroscopy was split from the whole frozen tumoral mass submerged in liquid nitrogen.…”

“…Metabolically aggressive tumors exhibit higher levels of metabolites associated to the aforementioned pathways, among others. Based on this metabolic aggressiveness, it is possible to define new molecular subgroups of benign meningioma [9].…”

Genomic and Metabolomic Profile Associated to Microalbuminuria

“…The study of small-molecule metabolites in biological fluids with NMR spectroscopy ( 1 H-NMR spectra), a fast and reproducible technique, may be useful for understanding metabolic imbalances and for detecting previously unsuspected links to pathological conditions [11], [12]. Recently studies using metabolomics have been applied to identify a discriminatory metabolite profile in a large number of diseases [13], [14], [15]. Up to now no information about the link between metabolomic profiles and UAE in the general population has been provided.…”