Evaluation of rs1957106 Polymorphism of NF-κBI in Glioblastoma Multiforme in Isfahan, Iran

Document Type : Original Article

Authors

1 Department of General Medicine, Isfahan Cardiovascular Research Institute, Isfahan University of Medical Sciences, Isfahan, Iran

2 Department of Applied Physiology Research Center, Isfahan Cardiovascular Research Institute, Isfahan University of Medical Sciences, Isfahan, Iran

3 Department of Physiology, School of Medicine, Isfahan University of Medical Sciences, Isfahan, Iran

Abstract

Background: The kB family of nuclear factor (NF-κB) is a series of transcription factors that plays a key role in regulation of immunity, cell growth, and apoptosis and is considered as the main downstream component of epidermal growth factor receptor for which there are evidence of excessive activity in most cases of glioblastoma multiform (GBM). Thus, the current information has gained evidence on NF-κBIA tumor suppressor role in GMB. SNP rs1957106 was diagnosed as a new polymorphism which affected the expression of NF-κBI and causes activation of NF-κB in GBM patients. Materials and Methods: This study was conducted on 100 cases of GBM including 47 paraffin-embedded brain tissue samples and 53 blood samples from another 53 GBM patients and 150 controls. The NF-κBI rs1957106 SNP was identified by the NCBI, and genotyping was performed by high-resolution melt (HRM) assay. Melt curves from HRM which suspected to single-nucleotide polymorphism (SNP) were selected and subjected to direct sequencing. Results: The distribution of allele A of NF-κβ gene in patients with GBM with 31% was not significantly different from healthy participants (27.3%) (P = 0.375). Furthermore, the distribution of AG and GG genotypes in comparison with AA genotypes did not show a significant correlation with GBM incidence (P > 0.05). Conclusion: Findings of the present study provide evidence that the rs1957106 SNP in NF-κBIA is found more in GBM patients, but it was not statistically significant. As there are conflicting studies showing significant higher rate of this SNP in GBM, further study is suggested.

Keywords

1.
Buckner JC. Factors influencing survival in high-grade gliomas. Semin Oncol 2003;30:10-4.  Back to cited text no. 1
    
2.
Stupp R, Mason WP, van den Bent MJ, Weller M, Fisher B, Taphoorn MJ, et al. Radiotherapy plus concomitant and adjuvant temozolomide for glioblastoma. N Engl J Med 2005;352:987-96.  Back to cited text no. 2
    
3.
Wen PY, Kesari S. Malignant gliomas in adults. N Engl J Med 2008;359:492-507.  Back to cited text no. 3
    
4.
DeAngelis LM. Brain tumors. N Engl J Med 2001;344:114-23.  Back to cited text no. 4
    
5.
Walker MD, Green SB, Byar DP, Alexander E Jr., Batzdorf U, Brooks WH, et al. Randomized comparisons of radiotherapy and nitrosoureas for the treatment of malignant glioma after surgery. N Engl J Med 1980;303:1323-9.  Back to cited text no. 5
    
6.
Parsa AT, Waldron JS, Panner A, Crane CA, Parney IF, Barry JJ, et al. Loss of tumor suppressor PTEN function increases B7-H1 expression and immunoresistance in glioma. Nat Med 2007;13:84-8.  Back to cited text no. 6
    
7.
Louis DN, Ohgaki H, Wiestler OD, Cavenee WK, Burger PC, Jouvet A, et al. The 2007 WHO classification of tumours of the central nervous system. Acta Neuropathol 2007;114:97-109.  Back to cited text no. 7
    
8.
Lv S, Zhang J, Han M, Wang W, Zhang Y, Zhuang D, et al. Nucleolin promotes TGF-β signaling initiation via TGF-β receptor I in glioblastoma. J Mol Neurosci 2015;55:1-6.  Back to cited text no. 8
    
9.
Parsons DW, Jones S, Zhang X, Lin JC, Leary RJ, Angenendt P, et al. An integrated genomic analysis of human glioblastoma multiforme. Science 2008;321:1807-12.  Back to cited text no. 9
    
10.
Yan H, Parsons DW, Jin G, McLendon R, Rasheed BA, Yuan W, et al. IDH1 and IDH2 mutations in gliomas. N Engl J Med 2009;360:765-73.  Back to cited text no. 10
    
11.
Phillips HS, Kharbanda S, Chen R, Forrest WF, Soriano RH, Wu TD, et al. Molecular subclasses of high-grade glioma predict prognosis, delineate a pattern of disease progression, and resemble stages in neurogenesis. Cancer Cell 2006;9:157-73.  Back to cited text no. 11
    
12.
Bredel M, Scholtens DM, Harsh GR, Bredel C, Chandler JP, Renfrow JJ, et al. A network model of a cooperative genetic landscape in brain tumors. JAMA 2009;302:261-75.  Back to cited text no. 12
    
13.
Yadav AK, Renfrow JJ, Scholtens DM, Xie H, Duran GE, Bredel C, et al. Monosomy of chromosome 10 associated with dysregulation of epidermal growth factor signaling in glioblastomas. JAMA 2009;302:276-89.  Back to cited text no. 13
    
14.
McLendon R, Friedman A, Bigner D, Van Meir EG, Brat DJ, Mastrogianakis GM. Comprehensive genomic characterization defines human glioblastoma genes and core pathways. Nature 2008;455:1061-8.  Back to cited text no. 14
    
15.
Watanabe K, Tachibana O, Sata K, Yonekawa Y, Kleihues P, Ohgaki H, et al. Overexpression of the EGF receptor and p53 mutations are mutually exclusive in the evolution of primary and secondary glioblastomas. Brain Pathol 1996;6:217-23.  Back to cited text no. 15
    
16.
Bargou RC, Leng C, Krappmann D, Emmerich F, Mapara MY, Bommert K, et al. High-level nuclear NF-kappa B and oct-2 is a common feature of cultured Hodgkin/Reed-Sternberg cells. Blood 1996;87:4340-7.  Back to cited text no. 16
    
17.
Grüssel T, Busch W. Experimental studies of the effect of peracetic acid on the endometrium of cattle. Tierarztl Pra×1997;25:28-34.  Back to cited text no. 17
    
18.
Barkett M, Gilmore TD. Control of apoptosis by Rel/NF-kappaB transcription factors. Oncogene 1999;18:6910-24.  Back to cited text no. 18
    
19.
May MJ, Ghosh S. Signal transduction through NF-kappa B. Immunol Today 1998;19:80-8.  Back to cited text no. 19
    
20.
Chiao PJ, Miyamoto S, Verma IM. Autoregulation of I kappa B alpha activity. Proc Natl Acad Sci U S A 1994;91:28-32.  Back to cited text no. 20
    
21.
Baeuerle PA, Baltimore D. NF-kappa B: Ten years after. Cell 1996;87:13-20.  Back to cited text no. 21
    
22.
Matthews JR, Nicholson J, Jaffray E, Kelly SM, Price NC, Hay RT, et al. Conformational changes induced by DNA binding of NF-kappa B. Nucleic Acids Res 1995;23:3393-402.  Back to cited text no. 22
    
23.
Roulston A, Lin R, Beauparlant P, Wainberg MA, Hiscott J. Regulation of human immunodeficiency virus type 1 and cytokine gene expression in myeloid cells by NF-kappa B/Rel transcription factors. Microbiol Rev 1995;59:481-505.  Back to cited text no. 23
    
24.
Jacobs MD, Harrison SC. Structure of an IkappaBalpha/NF-kappaB complex. Cell 1998;95:749-58.  Back to cited text no. 24
    
25.
Spink CF, Gray LC, Davies FE, Morgan GJ, Bidwell JL. Haplotypic structure across the I kappa B alpha gene (NFKBIA) and association with multiple myeloma. Cancer Lett 2007;246:92-9.  Back to cited text no. 25
    
26.
Krappmann D, Emmerich F, Kordes U, Scharschmidt E, Dörken B, Scheidereit C, et al. Molecular mechanisms of constitutive NF-kappaB/Rel activation in Hodgkin/Reed-sternberg cells. Oncogene 1999;18:943-53.  Back to cited text no. 26
    
27.
Cabannes E, Khan G, Aillet F, Jarrett RF, Hay RT. Mutations in the ikBa gene in hodgkin's disease suggest a tumour suppressor role for ikappaBalpha. Oncogene 1999;18:3063-70.  Back to cited text no. 27
    
28.
Zhao Z, Zhong X, Wu T, Yang T, Chen G, Xie X, et al. Identification of a NFKBIA polymorphism associated with lower NFKBIA protein levels and poor survival outcomes in patients with glioblastoma multiforme. Int J Mol Med 2014;34:1233-40.  Back to cited text no. 28
    
29.
Emmerich F, Meiser M, Hummel M, Demel G, Foss HD, Jundt F, et al. Overexpression of I kappa B alpha without inhibition of NF-kappaB activity and mutations in the I kappa B alpha gene in Reed-Sternberg cells. Blood 1999;94:3129-34.  Back to cited text no. 29
    
30.
Jungnickel B, Staratschek-Jox A, Bräuninger A, Spieker T, Wolf J, Diehl V, et al. Clonal deleterious mutations in the IkappaBalpha gene in the malignant cells in Hodgkin's lymphoma. J Exp Med 2000;191:395-402.  Back to cited text no. 30
    
31.
Lake A, Shield LA, Cordano P, Chui DT, Osborne J, Crae S, et al. Mutations of NFKBIA, encoding IkappaB alpha, are a recurrent finding in classical Hodgkin lymphoma but are not a unifying feature of non-EBV-associated cases. Int J Cancer 2009;125:1334-42.  Back to cited text no. 31
    
32.
Sjöblom T, Jones S, Wood LD, Parsons DW, Lin J, Barber TD, et al. The consensus coding sequences of human breast and colorectal cancers. Science 2006;314:268-74.  Back to cited text no. 32
    
33.
Gao J, Pfeifer D, He LJ, Qiao F, Zhang Z, Arbman G, et al. Association of NFKBIA polymorphism with colorectal cancer risk and prognosis in Swedish and Chinese populations. Scand J Gastroenterol 2007;42:345-50.  Back to cited text no. 33
    
34.
Osborne J, Lake A, Alexander FE, Taylor GM, Jarrett RF. Germline mutations and polymorphisms in the NFKBIA gene in Hodgkin lymphoma. Int J Cancer 2005;116:646-51.  Back to cited text no. 34
    
35.
He Y, Zhang H, Yin J, Xie J, Tan X, Liu S, et al. IkappaBalpha gene promoter polymorphisms are associated with hepatocarcinogenesis in patients infected with hepatitis B virus genotype C. Carcinogenesis 2009;30:1916-22.  Back to cited text no. 35
    
36.
Bu H, Rosdahl I, Sun XF, Zhang H. Importance of polymorphisms in NF-kappaB1 and NF-kappaBIalpha genes for melanoma risk, clinicopathological features and tumor progression in Swedish melanoma patients. J Cancer Res Clin Oncol 2007;133:859-66.  Back to cited text no. 36
    
37.
Liu X, Yu H, Yang W, Zhou X, Lu H, Shi D, et al. Mutations of NFKBIA in biopsy specimens from Hodgkin lymphoma. Cancer Genet Cytogenet 2010;197:152-7.  Back to cited text no. 37
    
38.
Parker KM, Ma MH, Manyak S, Altamirano CV, Tang YM, Frantzen M, et al. Identification of polymorphisms of the IkappaBalpha gene associated with an increased risk of multiple myeloma. Cancer Genet Cytogenet 2002;137:43-8.  Back to cited text no. 38
    
39.
Raychaudhuri B, Han Y, Lu T, Vogelbaum MA. Aberrant constitutive activation of nuclear factor kappaB in glioblastoma multiforme drives invasive phenotype. J Neurooncol 2007;85:39-47.  Back to cited text no. 39
    
40.
Nagai S, Washiyama K, Kurimoto M, Takaku A, Endo S, Kumanishi T, et al. Aberrant nuclear factor-kappaB activity and its participation in the growth of human malignant astrocytoma. J Neurosurg 2002;96:909-17.  Back to cited text no. 40
    
41.
Tsunoda K, Kitange G, Anda T, Shabani HK, Kaminogo M, Shibata S, et al. Expression of the constitutively activated RelA/NF-kappaB in human astrocytic tumors and the in vitro implication in the regulation of urokinase-type plasminogen activator, migration, and invasion. Brain Tumor Pathol 2005;22:79-87.  Back to cited text no. 41
    
42.
Bredel M, Scholtens DM, Yadav AK, Alvarez AA, Renfrow JJ, Chandler JP, et al. NFKBIA deletion in glioblastomas. N Engl J Med 2011;364:627-37.  Back to cited text no. 42