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International Journal of Molecular Medicine
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Print ISSN: 1107-3756 Online ISSN: 1791-244X
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May 2013 Volume 31 Issue 5

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International Journal of Molecular Medicine is an international journal devoted to molecular mechanisms of human disease.

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Article

Genotype analysis of the NRF2 gene mutation in lung cancer

  • Authors:
    • Hidefumi Sasaki
    • Ayumi Suzuki
    • Masayuki Shitara
    • Yu Hikosaka
    • Katsuhiro Okuda
    • Satoru Moriyama
    • Motoki Yano
    • Yoshitaka Fujii
  • View Affiliations / Copyright

    Affiliations: Department of Oncology, Immunology and Surgery, Nagoya City University Graduate School of Medical Sciences, Nagoya 467-8601, Japan
  • Pages: 1135-1138
    |
    Published online on: March 28, 2013
       https://doi.org/10.3892/ijmm.2013.1324
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Abstract

Nuclear factor (erythroid derived 2)-like 2 (NRF2, gene name NFE2L2) gene mutations have been previously identified in lung cancers. The constitutive activation of NRF2 resulting from gene mutations has been correlated with the poor prognosis of patients with squamous cell lung cancer. However, DNA sequencing using PCR methods described to date is time-consuming and requires significant quantities of DNA. Thus, this existing approach is not suitable for a routine pre-therapeutic screening program. We genotyped the NRF2 gene mutation status in 262 surgically treated lung cancer cases using LightCycler analysis. The presence of the NRF2 gene mutation was confirmed by direct sequencing. We detected 6 cases (2.3%) with NRF2 gene mutations in our cohort, particularly smokers (P=0.04) with squamous histology (P=0.0001). NRF2 gene mutations were present in 10% (6/60) of the lung squamous cell carcinoma (SqCC) cases. The NRF2 gene mutation was exclusive of epidermal growth factor receptor mutations. The NRF2 gene mutation occurred with a tendency towards a higher frequency in male patients. Patients with the NRF2 gene mutation (n=22, 11 succumbed to disease) had a significantly worse prognosis when compared with the patients with the wild-type NRF2 gene (n=521, 98 succumbed to disease) from a larger cohort study (log-rank test, P<0.0001) even upon multivariate analysis. In our study, NRF2 gene mutations played a role in the prognosis of patients with SqCC of the lung.
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1 

World Health Organization. Cancer. Fact Sheet. 297:http://www.who.int/mediacentre/factsheets/fs297/en/. Accessed February, 2012

2 

Paez JG, Janne PA, Lee JC, et al: EGFR mutations in lung cancer: correlation with clinical response to gefitinib therapy. Science. 304:1497–1500. 2004. View Article : Google Scholar : PubMed/NCBI

3 

Lynch TJ, Bell DW, Sordella R, et al: Activating mutations in the epidermal growth factor receptor underlying responsiveness of non-small-cell lung cancer to gefitinib. N Engl J Med. 350:2129–2139. 2004. View Article : Google Scholar : PubMed/NCBI

4 

Soda H, Choi YL, Enomoto M, et al: Identification of the transforming EML4-ALK fusion gene in non-small-cell lung cancer. Nature. 448:561–566. 2007. View Article : Google Scholar : PubMed/NCBI

5 

Lipson D, Capelletti M, Yelensky R, et al: Identification of new ALK and RET gene fusions from colorectal and lung cancer biopsies. Nat Med. 18:382–384. 2012. View Article : Google Scholar : PubMed/NCBI

6 

Kohno T, Ishikawa H, Totoki Y, et al: KIF5B-RET fusions in lung adenocarcinoma. Nat Med. 18:375–377. 2012. View Article : Google Scholar : PubMed/NCBI

7 

Takeuchi K, Soda M, Togashi Y, et al: RET, ROS and ALK fusions in lung cancer. Nat Med. 18:378–381. 2012. View Article : Google Scholar : PubMed/NCBI

8 

Cancer Genome Atlas Research Network. Comprehensive genomic characterization of squamous cell cancers. Nature. 489:519–525. 2012. View Article : Google Scholar : PubMed/NCBI

9 

Itoh K, Chiba T, Takahashi S, et al: An Nrf2/small Maf heterodimer mediates the induction of phase II detoxifying enzyme genes through antioxidant response elements. Biochem Biophys Res Commun. 236:313–322. 1997. View Article : Google Scholar : PubMed/NCBI

10 

Rushmore TH and Kong AN: Pharmacogenomics, regulation and signaling pathways of phase I and II detoxifying enzymes. Curr Drug Metab. 3:481–490. 2002. View Article : Google Scholar : PubMed/NCBI

11 

Ngyyen T, Yang CS and Pickett CB: The pathways and molecular mechanisms regulating Nrf2 activation in response to chemical stress. Free Radic Biol Med. 37:433–441. 2004. View Article : Google Scholar : PubMed/NCBI

12 

Fahey JW and Kensler TW: Role of dietary supplements/nutraceuticals in chemoprevention through induction of cytoprotective enzymes. Chem Res Toxicol. 20:572–576. 2007. View Article : Google Scholar : PubMed/NCBI

13 

Kensler TW, Wakabayashi N and Biswal S: Cell survival responses to environmental stresses via the Keap1-Nrf2-ARE pathway. Annu Rev Pharmacol Toxicol. 47:89–116. 2007. View Article : Google Scholar : PubMed/NCBI

14 

Singh A, Boldin-Adamsky S, Thimmulappa RK, et al: RNAi-mediated silencing of nuclear factor erythroid-2-related factor 2 gene expression in non-small cell lung cancer inhibits tumor growth and increases efficacy of chemotherapy. Cancer Res. 68:7975–7984. 2008. View Article : Google Scholar

15 

Arisawa T, Tahara T, Shibata T, et al: Nrf2 gene promoter polymorphism and gastric carcinogenesis. Hepatogastroenterology. 55:750–754. 2008.PubMed/NCBI

16 

Shibata T, Ohta T, Tong KI, et al: Cancer related mutations in NRF2 impair its recognition by Keap1-Cul3 E3 ligase and promote malignancy. Proc Natl Acad Sci USA. 105:13568–13573. 2008. View Article : Google Scholar : PubMed/NCBI

17 

Sasaki H, Hikosaka Y, Okuda K, et al: NFE2L2 gene mutation in male Japanese squamous cell carcinoma of the lung. J Thorac Oncol. 5:786–789. 2010. View Article : Google Scholar : PubMed/NCBI

18 

Wittwer CT, Herrmann MG, Moss AA and Rasmussen RP: Continuous fluorescence monitoring of rapid cycle DNA amplification. Biotechniques. 22:130–138. 1997.PubMed/NCBI

19 

Pals G, Pindolia K and Worsham MJ: A rapid sensitive approach to mutation detection using real-time polymerase chain reaction and melting curve analyses, using BRCA1 as an example. Mol Diagn. 4:241–246. 1999. View Article : Google Scholar

20 

Sasaki H, Endo K, Konishi A, et al: EGFR mutation status in Japanese lung cancer patients: genotyping analysis using LightCycler. Clin Cancer Res. 11:2924–2929. 2005. View Article : Google Scholar : PubMed/NCBI

21 

Itoh K, Wakabayashi N, Katoh Y, et al: Keap1 represses nuclear activation of antioxidant responsive elements by Nrf2 through binding to the amino-terminal Neh2 domain. Genes Dev. 13:76–86. 1999. View Article : Google Scholar : PubMed/NCBI

22 

Sasaki H, Shimizu S, Endo K, et al: EGFR and erbB2 mutation status in Japanese lung cancer patients. Int J Cancer. 118:180–184. 2006. View Article : Google Scholar : PubMed/NCBI

23 

Yokota K, Sasaki H, Okuda K, et al: KIF5B/RET fusion gene in surgically-treated Japanese adenocarcinoma of the lung. Oncol Rep. 28:1187–1192. 2012.PubMed/NCBI

24 

Hu Y, Ju Y, Lin D, et al: Mutation of the Nrf2 gene in non-small cell lung cancer. Mol Biol Rep. 39:4743–4747. 2012. View Article : Google Scholar : PubMed/NCBI

25 

Ahrendt SA, Decker PA, Alawi EA, et al: Cigarette smoking is strongly associated with mutation of the Kras gene in patients with primary adenocarcinoma of the lung. Cancer. 92:1525–1530. 2001. View Article : Google Scholar : PubMed/NCBI

26 

Stratton MR, Campbell PJ and Futreal PA: The cancer genome. Nature. 458:719–724. 2009. View Article : Google Scholar

27 

Muller T and Hengstermann A: Nrf2: friend and foe in preventing cigarette smoking-dependent lung disease. Chem Res Toxicol. 25:1805–1824. 2012. View Article : Google Scholar : PubMed/NCBI

28 

Semenza GL: Targeting HIF-1 for cancer therapy. Nat Rev Cancer. 3:721–732. 2003. View Article : Google Scholar

29 

Zhou J, Scmid T, Schnitzer S and Brune B: Tumor hypoxia and cancer progression. Cancer Lett. 237:10–21. 2006. View Article : Google Scholar

30 

Homma S, Ishii Y, Morishima Y, et al: Nrf2 enhances cell proliferation and resistance to anticancer drugs in human lung cancer. Clin Cancer Res. 15:3423–3432. 2009. View Article : Google Scholar : PubMed/NCBI

31 

Sasaki H, Shitara M, Yokota K, et al: MRP3 gene expression correlates with NRF2 mutations in lung squamous cell carcinomas. Mol Med Rep. 6:705–708. 2012.PubMed/NCBI

32 

Leinonen HM, Ruotsalainen AK, Määttä AM, et al: Oxidative stress-regulated lentiviral TK/GCV gene therapy for lung cancer treatment. Cancer Res. 72:6227–6235. 2012. View Article : Google Scholar : PubMed/NCBI

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Copy and paste a formatted citation
Spandidos Publications style
Sasaki H, Suzuki A, Shitara M, Hikosaka Y, Okuda K, Moriyama S, Yano M and Fujii Y: Genotype analysis of the NRF2 gene mutation in lung cancer. Int J Mol Med 31: 1135-1138, 2013.
APA
Sasaki, H., Suzuki, A., Shitara, M., Hikosaka, Y., Okuda, K., Moriyama, S. ... Fujii, Y. (2013). Genotype analysis of the NRF2 gene mutation in lung cancer. International Journal of Molecular Medicine, 31, 1135-1138. https://doi.org/10.3892/ijmm.2013.1324
MLA
Sasaki, H., Suzuki, A., Shitara, M., Hikosaka, Y., Okuda, K., Moriyama, S., Yano, M., Fujii, Y."Genotype analysis of the NRF2 gene mutation in lung cancer". International Journal of Molecular Medicine 31.5 (2013): 1135-1138.
Chicago
Sasaki, H., Suzuki, A., Shitara, M., Hikosaka, Y., Okuda, K., Moriyama, S., Yano, M., Fujii, Y."Genotype analysis of the NRF2 gene mutation in lung cancer". International Journal of Molecular Medicine 31, no. 5 (2013): 1135-1138. https://doi.org/10.3892/ijmm.2013.1324
Copy and paste a formatted citation
x
Spandidos Publications style
Sasaki H, Suzuki A, Shitara M, Hikosaka Y, Okuda K, Moriyama S, Yano M and Fujii Y: Genotype analysis of the NRF2 gene mutation in lung cancer. Int J Mol Med 31: 1135-1138, 2013.
APA
Sasaki, H., Suzuki, A., Shitara, M., Hikosaka, Y., Okuda, K., Moriyama, S. ... Fujii, Y. (2013). Genotype analysis of the NRF2 gene mutation in lung cancer. International Journal of Molecular Medicine, 31, 1135-1138. https://doi.org/10.3892/ijmm.2013.1324
MLA
Sasaki, H., Suzuki, A., Shitara, M., Hikosaka, Y., Okuda, K., Moriyama, S., Yano, M., Fujii, Y."Genotype analysis of the NRF2 gene mutation in lung cancer". International Journal of Molecular Medicine 31.5 (2013): 1135-1138.
Chicago
Sasaki, H., Suzuki, A., Shitara, M., Hikosaka, Y., Okuda, K., Moriyama, S., Yano, M., Fujii, Y."Genotype analysis of the NRF2 gene mutation in lung cancer". International Journal of Molecular Medicine 31, no. 5 (2013): 1135-1138. https://doi.org/10.3892/ijmm.2013.1324
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