¹Instituto de Investigaciones Biomédicas (CSIC), Arturo Duperier, 4, 28029-Madrid, Spain

²Department of Neurosurgery of Hospital del Rio Hortega, Valladolid Madrid, Spain

³Department of Neurosurgery, Clínica Puerta de Hierro, Madrid, Spain

⁴Department of Anatomical Pathology, Fundación Jiménez Diaz, Madrid, Spain

^aAuthor for correspondence

^bCurrent address: Laboratorio de Genetica Molecular y Citogenetica Humana, Facultad de Medicina, Pontificia Universidad Católica de Ecuador, Apartado 17-1-2184 Quito, Ecuador

Formation of meningiomas and their progression to malignancy may be a multi-step process, implying accumulation of genetic mutations at specific loci. To determine the relationship between early NF2 gene inactivation and the molecular mechanisms that may contribute to meningioma tumor progression, we have performed deletion mapping analysis at chromosomes 1, 14 and 22 in a series of 81 sporadic meningiomas (54 grade I (typical), 25 grade II (atypical) and two grade III (anaplastic)), which were also studied for NF2 gene mutations. Single-strand conformational polymorphism analysis was used to identify 11 mutations in five of the eight exons of the NF2 gene studied. All 11 tumors displayed loss of heterozygosity (LOH) for chromosome 22 markers; this anomaly was also detected in 33 additional tumors. Twenty-nine and 23 cases were characterized by LOH at 1p and 14q, respectively, mostly corresponding to aggressive tumors that also generally displayed LOH 22. All three alterations were detected in association in seven grade II and two grade III meningiomas, corroborating the hypothesis that the formation of aggressive meningiomas follows a multi-step tumor progression model.

meningiomas; NF2; allelic losses; tumor progression; 1p and 14q deletion mapping