title: Association between mutation of the NF2 gene and monosomy 22 in menopausal women with sporadic meningiomas.
abstract: BACKGROUND
  Meningioma was the first solid tumor shown to contain a recurrent genetic alteration e.g. monosomy 22/del(22q), NF2 being the most relevant gene involved. Although monosomy 22/del(22q) is present in half of all meningiomas, and meningiomas frequently carry NF2 mutations, no study has been reported so far in which both alterations are simultaneously assessed and correlated with the features of the disease.
  
  
  METHODS
  Here, we analyzed the frequency of both copy number changes involving chromosome 22 and NF2 mutations in 20 sporadic meningiomas using high-density SNP-arrays, interphase-FISH and PCR techniques.
  
  
  RESULTS
  Our results show a significant frequency of NF2 mutations (6/20 patients, 30%), most of which (5/6) had not been previously reported in sporadic meningiomas. NF2 mutations involved five different exons and led to a truncated protein (p.Leu163CysfsX46, p.Phe62LeufsX61, p.Asp281MetfsX15, p.Phe285LeufsX11, p.Gln389ArgfsX37) and an in frame deletion of Phe119. Interestingly, all NF2 mutated cases were menopausal women with monosomy 22 but not del(22q).
  
  
  CONCLUSIONS
  These results confirm and extend on previous observations about the high frequency and heterogeneity of NF2 mutations in sporadic meningiomas and indicate they could be restricted to a well-defined cytogenetic and clinical subgroup of menopausal women. Further studies in large series of patients are required to confirm our observations.
authors.affiliation: Instituto de Estudios Ciencias de la Salud de Castilla y León (IECSCYL), Soria, Spain. taberner@usal.es.
authors.forename: MariaDolores
authors.initials: M
authors.lastname: Tabernero
authors.forename: María
authors.initials: M
authors.lastname: Jara-Acevedo
authors.forename: Ana B
authors.initials: AB
authors.lastname: Nieto
authors.forename: Arancha Rodríguez
authors.initials: AR
authors.lastname: Caballero
authors.forename: Alvaro
authors.initials: A
authors.lastname: Otero
authors.forename: Pablo
authors.initials: P
authors.lastname: Sousa
authors.forename: Jesús
authors.initials: J
authors.lastname: Gonçalves
authors.forename: Patricia H
authors.initials: PH
authors.lastname: Domingues
authors.forename: Alberto
authors.initials: A
authors.lastname: Orfao
mesh_terms: D000368:Aged; D002872:Chromosome Deletion; D002892:Chromosomes, Human, Pair 22; D005091:Exons; D005260:Female; D018628:Gene Dosage; D006801:Humans; D019656:Loss of Heterozygosity; D008297:Male; D008577:Meningeal Neoplasms / Q000235:genetics*; D008579:Meningioma / Q000235:genetics*; D008593:Menopause; D008875:Middle Aged; D009006:Monosomy / Q000235:genetics*; D009154:Mutation; D059645:Mutation Rate; D025581:Neurofibromin 2 / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide
chemical_list: D025581:Neurofibromin 2