A novel NOTCH3 mutation identified in patients with oral cancer by whole exome sequencing

  • Authors:
    • Yanjun Yi
    • Zhuowei Tian
    • Houyu Ju
    • Guoxin Ren
    • Jingzhou Hu
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  • Published online on: April 25, 2017     https://doi.org/10.3892/ijmm.2017.2965
  • Pages: 1541-1547
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Abstract

Oral cancer is a serious disease caused by environmental factors and/or susceptible genes. In the present study, in order to identify useful genetic biomarkers for cancer prediction and prevention, and for personalized treatment, we detected somatic mutations in 5 pairs of oral cancer tissues and blood samples using whole exome sequencing (WES). Finally, we confirmed a novel nonsense single-nucleotide polymorphism (SNP; chr19:15288426A>C) in the NOTCH3 gene with sanger sequencing, which resulted in a N1438T mutation in the protein sequence. Using multiple in silico analyses, this variant was found to mildly damaging effects on the NOTCH3 gene, which was supported by the results from analyses using PANTHER, SNAP and SNPs&GO. However, further analysis using Mutation Taster revealed that this SNP had a probability of 0.9997 to be ‘disease causing’. In addition, we performed 3D structure simulation analysis and the results suggested that this variant had little effect on the solubility and hydrophobicity of the protein and thus on its function; however, it decreased the stability of the protein by increasing the total energy following minimization (-1,051.39 kcal/mol for the mutant and -1,229.84 kcal/mol for the native) and decreasing one stabilizing residue of the protein. Less stability of the N1438T mutant was also supported by analysis using I-Mutant with a DDG value of -1.67. Overall, the present study identified and confirmed a novel mutation in the NOTCH3 gene, which may decrease the stability of NOTCH3, and may thus prove to be helpful in cancer prognosis.
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June-2017
Volume 39 Issue 6

Print ISSN: 1107-3756
Online ISSN:1791-244X

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Spandidos Publications style
Yi Y, Tian Z, Ju H, Ren G and Hu J: A novel NOTCH3 mutation identified in patients with oral cancer by whole exome sequencing. Int J Mol Med 39: 1541-1547, 2017.
APA
Yi, Y., Tian, Z., Ju, H., Ren, G., & Hu, J. (2017). A novel NOTCH3 mutation identified in patients with oral cancer by whole exome sequencing. International Journal of Molecular Medicine, 39, 1541-1547. https://doi.org/10.3892/ijmm.2017.2965
MLA
Yi, Y., Tian, Z., Ju, H., Ren, G., Hu, J."A novel NOTCH3 mutation identified in patients with oral cancer by whole exome sequencing". International Journal of Molecular Medicine 39.6 (2017): 1541-1547.
Chicago
Yi, Y., Tian, Z., Ju, H., Ren, G., Hu, J."A novel NOTCH3 mutation identified in patients with oral cancer by whole exome sequencing". International Journal of Molecular Medicine 39, no. 6 (2017): 1541-1547. https://doi.org/10.3892/ijmm.2017.2965