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RESEARCH PRODUCT

Cytogenetic analysis and metabolic profiling reveal a subgroup of benign meningiomas with chromosomal instabilities and aggressive metabolism

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description

Meningiomas add up to 30% of Central Nervous System (CNS) tumours. Atypical meningiomas show a high index of recurrence 5 years after complete resection. Sometimes, meningiomas with histological diagnosis of benign meningioma show genetics characteristics of atypical meningioma. Aberrations of chromosomes 1, 14, and 22 are the most frequently reported abnormalities in meningiomas. In this communication we used cytogenetic, FISH, and NMR metabolic profiling for a molecular characterization of a series of 46 meningiomas. Tumor samples were obtained from 46 patients with meningioma (36 benign and 12 atypical) from the Clinic Hospital of Valencia. Cytogenetic analyses were performed by short-term culture using standard methods. FISH analyses were performed using tissue microarrays and LSI 22q12 and LSI1p36/LSI1q25 probes. Metabolic profiling was performed on frozen tissue by HR-MAS (High resolution Magic Angle Spectroscopy). All samples were analyzed by post-HR-MAS histopathology to assess the tissue integrity and double validate histological diagnosis. Statistical analysis was performed using in-house MATLAB scripts and the PLS_toolbox statistical multivariate analysis library. Our cytogenetic and FISH results show a subgroup of fourteen benign meningiomas with complex karyotypes and chromosomal instability affecting one or more of the chromosomes 1, 2, 3, 7, 9, 10, and 22. FISH analysis shows that at least five of them have a 1p deletion. The recurrence rate of this group was higher than benign meningiomas without chromosomal instabilities, but lower than atypical meningiomas. The metabolic profile of this subgroup exhibits high levels of choline-containing compounds, lactate, glucose, and creatine, and low levels of taurine, myo-inositol, and some fatty acids when compared to the remaining benign meningiomas. The Principal Component Analysis of the metabolic profile also shows that this subgroup is closer to atypical meningioma than to benign meningioma without chromosomal instability. The genetic and metabolic profiles obtained for this new subgroup of meningiomas place them biochemically closer to atypical meningioma than to the conventional benign meningioma. The methodology used in this study may also open new possibilities for the diagnosis of meningioma. Financial support: Ministry of Science and Innovation of Spain (SAF2008-00270) and a Ramon y Cajal contract to DM. Grant FISPI061134I. EXPRESSION OF CHEMOKINE RECEPTOR CXCR3, CXCR4, AND CXCR7 AND THEIR RESPECTIVE LIGANDS IN RHABDOMYOSARCOMA