The association of NF2 (neurofibromin 2) gene polymorphism and the risk of medulloblastomas
To explore the relationship between NF2 promoter gene mutation and the risk of medulloblastomas (MBs). We collected tissues from 16 MB patients and 7 age-matched non-MB controls. Gene sequencing, qPCR (real-time quantitative polymerase chain reaction), IHC (immunohistochemistry), and WB (Western blot) were used to analyze the changes in the NF2 gene sequence and expression between patients and controls. We found that NF2 promoter gene mutations occurred in MB patients. The NF2 mRNA expression was higher in the controls than in patients (p = 0.03 < 0.05); however, the results of IHC and WB demonstrated that the NF2 protein expression was significantly higher in patients than in the controls (IHC: p = 0.0001; WB: p = 0.01). There was no significant difference in the CRL4 mRNA and protein levels. In addition, NF2 protein was mainly expressed in the nucleus in MB patients, while the NF2 protein was mainly expressed in the cytoplasm in the controls. NF2 promoter mutations exist in MB patients. NF2 mRNA expression was higher in controls than patients; whereas NF2 protein level was higher in patients than in controls.
KeywordsNF2 (neurofibromin2) Medulloblastomas (MB) Quantitative real-time PCR (qPCR) Western blot (WB) Promoter mutation
No funding was received for this research.
Compliance with ethical standards
Conflict of interest
The authors declare that they have no conflict of interest.
All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.
Informed consent was obtained from all individual participants or their guardians included in the study.
- 1.Louis DN, Perry A, Reifenberger G, von Deimling A, Figarella-Branger D, Cavenee WK, Ohgaki H, Wiestler OD, Kleihues P, Ellison DW (2016) The 2016 World Health Organization classification of tumors of the central nervous system: a summary. Acta Neuropathol 131(6):803–820. https://doi.org/10.1007/s00401-016-1545-1 CrossRefPubMedGoogle Scholar
- 6.Gupta T, Jalali R, Goswami S, Nair V, Moiyadi A, Epari S, Sarin R (2012) Early clinical outcomes demonstrate preserved cognitive function in children with average-risk medulloblastoma when treated with hyperfractionated radiation therapy. Int J Radiat Oncol Biol Phys 83(5):1534–1540CrossRefPubMedGoogle Scholar
- 7.Madeleine MM, Anttila T, Schwartz SM, Saikku P, Leinonen M, Carter JJ, Wurscher M, Johnson LG, Galloway DA, Daling JR (2007) Risk of cervical cancer associated with chlamydia trachomatis antibodies by histology, HPV type and HPV cofactors. Int J Cancer 120(3):650–655. https://doi.org/10.1002/ijc.22325 CrossRefPubMedPubMedCentralGoogle Scholar
- 16.Ongaratti BR, Silva CB, Trott G, Haag T, Leães CG, Ferreira NP, Oliveira MC, Pereiralima JF (2016) Expression of merlin, NDRG2, ERBB2, and c-MYC in meningiomas: relationship with tumor grade and recurrence. Braz J Med Biol Res = Revista brasileira de pesquisas medicas e biologicas / Sociedade Brasileira de Biofisica [et al] 49 (4)Google Scholar
- 17.Evans DG, Huson SM, Donnai D, Neary W, Blair V, Teare D, Newton V, Strachan T, Ramsden R, Harris R (1992) A genetic study of type 2 neurofibromatosis in the United Kingdom. I. Prevalence, mutation rate, fitness, and confirmation of maternal transmission effect on severity. J Med Genet 29(12):841–846CrossRefPubMedPubMedCentralGoogle Scholar
- 28.Zhao B, Wei X, Li W, Udan RS, Yang Q, Kim J, Xie J, Ikenoue T, Yu J, Li L, Zheng P, Ye K, Chinnaiyan A, Halder G, Lai Z-C, Guan K-L (2007) Inactivation of YAP oncoprotein by the hippo pathway is involved in cell contact inhibition and tissue growth control. Genes Dev 21(21):2747–2761CrossRefPubMedPubMedCentralGoogle Scholar
- 29.Deng L, Ma C, Yuan Q, Gao X, Yang C (2005) Total RNA extracted from brain tissue of rat by trizol reagent. J Luzhou Med College 28(6):505–506Google Scholar
- 31.Vinagre J, Almeida A, Pópulo H, Batista R, Lyra J, Pinto V, Coelho R, Celestino R, Prazeres H, Lima L (2013) Frequency of TERT promoter mutations in human cancers. Nat Commun 4(4):405–415Google Scholar
- 33.Kendrick N (2014) A gene's mRNA level does not usually predict its protein level. Kendrick Laboratories, Inc, 1202 Ann St, Madison, WI 53713Google Scholar
- 35.Yi C, Troutman S, Fera D, Stemmerrachamimov A, Avila JL, Christian N, Persson NL, Shimono A, Speicher DW, Marmorstein R (2011) A tight junction-associated Merlin-angiomotin complex mediates Merlin’s regulation of mitogenic signaling and tumor suppressive functions. Cancer Cell 19(4):527–540CrossRefPubMedPubMedCentralGoogle Scholar
- 41.Zhao Z, Lu T, Zhang N, Wang Y, He X, Zhang B, Huang J (2015) Study on the expression of neurofibromatosis 2 gene and its dinieal significance in primary liver cancer. Int J Clin Exp Med 7:535–538Google Scholar