NF2 gene mutations and allelic status of 1p, 14q and 22q in sporadic meningiomas

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, w e have performed deletion mapping analysis at chromosomes 1, 14 and 22 in a series of 81 sporadic meningiomas (54 grade I(typical), 25 grade LI (atypi cal) and two grade III (anaplastic)), which were also studied for NF2 gene mutations. Single-strand conformational polymorphism analysis was used to i dentify 11 mutations in five of the eight exons of the NF2 gene studied. Al l 11 tumors displayed loss of heterozygosity (LOH) for chromosome 22 marker s; this anomaly was also detected in 33 additional tumors. Twenty-nine and 23 cases were characterized by LOH at 1p and 14q, respectively, mostly corr esponding to aggressive tumors that also generally displayed LOH 22. All th ree alterations were detected in association in seven grade II and two grad e III meningiomas, corroborating the hypothesis that the formation of aggre ssive meningiomas follows a multi-step tumor progression model.