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The role of NF2 gene mutations and pathogenesis-related proteins in sporadic vestibular schwannomas in young individuals

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Abstract

Vestibular schwannomas (VSs) are benign tumors arising from eighth cranial nerve and most often occur sporadically in individuals of middle age group. Sporadic VSs are rarely reported in the young population. In this study, we evaluated clinical behaviors of 12 young sporadic VSs by the statistical comparison with a matched series of 145 adult cases. We found that young tumors were characterized by an earlier onset of initial symptom, shorter duration from the first symptom to diagnosis, and larger tumor size than adult ones. Standard sequencing demonstrated the presence of NF2 mutations in eight tumors. All NF2 mutations identified were truncating mutations (nonsense, frameshift, and splicing-site mutations). Earlier formation of VSs in young patients was evidenced by the high incidence of NF2 mutations (66.7 %) far beyond our previous study in the adult case series (34.5 %). Furthermore, young tumors exhibited deficient merlin or heightened phosphorylated merlin that was subsequently demonstrated to be well correlated with increased tumor size. Finally, we compared protein levels of four pathogenesis-related molecules between young and adult group but there was no significant difference. These results led us to suggest that high frequency of NF2 mutations may play a critical role in early tumorigenesis of young VSs. Moreover, merlin deficiency or phosphorylation status of merlin was involved in their earlier development. Further study remains to fully understand the mechanism for the rapid growth of young VSs.

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Acknowledgments

This work was supported by the National Natural Science Foundation of China (Grant No. 81371086 to Zhaoyan Wang).

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Authors and Affiliations

  1. Department of Otolaryngology Head and Neck Surgery, Xinhua Hospital, School of Medicine, Shanghai Jiao Tong University, 1665 Kongjiang Road, Shanghai, 200092, China

    Hongsai Chen, Xiaoman Zhang, Zhihua Zhang, Tao Yang, Zhaoyan Wang & Hao Wu

  2. Ear Institute, School of Medicine, Shanghai Jiao Tong University, 1665 Kongjiang Road, Shanghai, 200092, China

    Hongsai Chen, Xiaoman Zhang, Zhihua Zhang, Tao Yang, Zhaoyan Wang & Hao Wu

Authors
  1. Hongsai Chen
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  2. Xiaoman Zhang
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  3. Zhihua Zhang
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  4. Tao Yang
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  5. Zhaoyan Wang
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  6. Hao Wu
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Corresponding authors

Correspondence to Zhaoyan Wang or Hao Wu.

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Hongsai Chen and Xiaoman Zhang have contributed equally to this work.

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Chen, H., Zhang, X., Zhang, Z. et al. The role of NF2 gene mutations and pathogenesis-related proteins in sporadic vestibular schwannomas in young individuals. Mol Cell Biochem 392, 145–152 (2014). https://doi.org/10.1007/s11010-014-2011-9

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  • DOI: https://doi.org/10.1007/s11010-014-2011-9

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