Association between mutation of the NF2 gene and monosomy 22 in menopausal women with sporadic meningiomas

BMC Medical Genetics

Alberto Orfao²  Patricia H Domingues²  Jesús Gonçalves¹  Pablo Sousa¹  Álvaro Otero¹  Arancha Rodríguez Caballero²  Ana B Nieto²  María Jara-Acevedo²  MariaDolores Tabernero² 

[1] Neurosurgery Service of the University Hospital of Salamanca, Salamanca, Spain;Centre for Cancer Research (CIC), Instituto de Biología Molecular (IBMCC), Centro superior de Investigaciones Científicas (CSIC), Universidad de Salamanca (USAL), Salamanca, Spain

关键词: Menopausal women;    Monosomy 22;    Sporadic meningiomas;    NF2 gene;    Mutation;   

Others  :  1122589
DOI  :  10.1186/1471-2350-14-114

 received in 2013-06-28, accepted in 2013-10-28,  发布年份 2013

【 摘 要 】

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.

【 授权许可】

   
2013 Tabernero et al.; licensee BioMed Central Ltd.

【 图 表 】

Figure 1.

Figure 2.

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