Association of epidermal growth factor receptor mutations with human papillomavirus 16/18 E6 oncoprotein expression in non-small cell lung cancer

Min Che Tung, Heng Hsiung Wu, Ya Wen Cheng, Lee Wang, Chih Yi Chen, Sauh Der Yeh, Tzu Chin Wu, Huei Lee

Research output: Contribution to journalArticle

12 Citations (Scopus)

Abstract

Background: Lung cancers in women, in nonsmokers, and in patients with adenocarcinoma from Asia have more prevalent mutations in the epidermal growth factor receptor (EGFR) gene than their counterparts. However, the etiology of EGFR mutations in this population remains unclear. The authors hypothesized that the human papillomavirus (HPV) type 16/18 (HPV16/18) E6 oncoprotein may contribute to EGFR mutations in Taiwanese patients with lung cancer. Methods: One hundred fifty-one tumors from patients with lung cancer were enrolled to determine HPV16/18 E6 and EGFR mutations using immunohistochemistry and direct sequencing, respectively. Levels of 8-oxo-7,8-dihydro-2′-deoxyguanosine (8-oxo-dG) in lung tumors and cells were evaluated using immunohistochemistry and liquid chromatography-mass spectrometry/mass spectrometry. An supF mutagenesis assay was used to determine H2O2-induced mutation rates of lung cancer cells with or without E6 expression. Results: Patients with E6-positive tumors had a greater frequency of EGFR mutations than those with E6-negative tumors (41% vs 20%; P =.006). Levels of 8-oxo-dG were correlated with EGFR mutations (36% vs 16%; P =.012). Two stable clones of E6-overexpressing H157 and CL-3 cells were established for the supF mutagenesis assay. The data indicated that the cells with high E6 overexpression had higher H2O2-induced SupF gene mutation rates compared with the cells that expressed lower levels of E6 and compared with vector control cells. Conclusions: HPV16/18 E6 may contribute in part to EGFR mutations in lung cancer, at least in the Taiwanese population.

Original languageEnglish
Pages (from-to)3367-3376
Number of pages10
JournalCancer
Volume119
Issue number18
DOIs
Publication statusPublished - Sep 15 2013

Fingerprint

Human papillomavirus 18
Human papillomavirus 16
Oncogene Proteins
Epidermal Growth Factor Receptor
Non-Small Cell Lung Carcinoma
Mutation
Lung Neoplasms
Mutation Rate
Mutagenesis
Neoplasms
Immunohistochemistry
erbB-1 Genes
Tandem Mass Spectrometry
Liquid Chromatography
Population
Adenocarcinoma
Clone Cells
Lung
Genes

Keywords

  • 8-dihydro-2& prime;-deoxyguanosine
  • 8-oxo-7
  • epidermal growth factor receptor
  • human papillomavirus
  • lung cancer
  • mutation

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Association of epidermal growth factor receptor mutations with human papillomavirus 16/18 E6 oncoprotein expression in non-small cell lung cancer. / Tung, Min Che; Wu, Heng Hsiung; Cheng, Ya Wen; Wang, Lee; Chen, Chih Yi; Yeh, Sauh Der; Wu, Tzu Chin; Lee, Huei.

In: Cancer, Vol. 119, No. 18, 15.09.2013, p. 3367-3376.

Research output: Contribution to journalArticle

Tung, Min Che ; Wu, Heng Hsiung ; Cheng, Ya Wen ; Wang, Lee ; Chen, Chih Yi ; Yeh, Sauh Der ; Wu, Tzu Chin ; Lee, Huei. / Association of epidermal growth factor receptor mutations with human papillomavirus 16/18 E6 oncoprotein expression in non-small cell lung cancer. In: Cancer. 2013 ; Vol. 119, No. 18. pp. 3367-3376.
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abstract = "Background: Lung cancers in women, in nonsmokers, and in patients with adenocarcinoma from Asia have more prevalent mutations in the epidermal growth factor receptor (EGFR) gene than their counterparts. However, the etiology of EGFR mutations in this population remains unclear. The authors hypothesized that the human papillomavirus (HPV) type 16/18 (HPV16/18) E6 oncoprotein may contribute to EGFR mutations in Taiwanese patients with lung cancer. Methods: One hundred fifty-one tumors from patients with lung cancer were enrolled to determine HPV16/18 E6 and EGFR mutations using immunohistochemistry and direct sequencing, respectively. Levels of 8-oxo-7,8-dihydro-2′-deoxyguanosine (8-oxo-dG) in lung tumors and cells were evaluated using immunohistochemistry and liquid chromatography-mass spectrometry/mass spectrometry. An supF mutagenesis assay was used to determine H2O2-induced mutation rates of lung cancer cells with or without E6 expression. Results: Patients with E6-positive tumors had a greater frequency of EGFR mutations than those with E6-negative tumors (41{\%} vs 20{\%}; P =.006). Levels of 8-oxo-dG were correlated with EGFR mutations (36{\%} vs 16{\%}; P =.012). Two stable clones of E6-overexpressing H157 and CL-3 cells were established for the supF mutagenesis assay. The data indicated that the cells with high E6 overexpression had higher H2O2-induced SupF gene mutation rates compared with the cells that expressed lower levels of E6 and compared with vector control cells. Conclusions: HPV16/18 E6 may contribute in part to EGFR mutations in lung cancer, at least in the Taiwanese population.",
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T1 - Association of epidermal growth factor receptor mutations with human papillomavirus 16/18 E6 oncoprotein expression in non-small cell lung cancer

AU - Tung, Min Che

AU - Wu, Heng Hsiung

AU - Cheng, Ya Wen

AU - Wang, Lee

AU - Chen, Chih Yi

AU - Yeh, Sauh Der

AU - Wu, Tzu Chin

AU - Lee, Huei

PY - 2013/9/15

Y1 - 2013/9/15

N2 - Background: Lung cancers in women, in nonsmokers, and in patients with adenocarcinoma from Asia have more prevalent mutations in the epidermal growth factor receptor (EGFR) gene than their counterparts. However, the etiology of EGFR mutations in this population remains unclear. The authors hypothesized that the human papillomavirus (HPV) type 16/18 (HPV16/18) E6 oncoprotein may contribute to EGFR mutations in Taiwanese patients with lung cancer. Methods: One hundred fifty-one tumors from patients with lung cancer were enrolled to determine HPV16/18 E6 and EGFR mutations using immunohistochemistry and direct sequencing, respectively. Levels of 8-oxo-7,8-dihydro-2′-deoxyguanosine (8-oxo-dG) in lung tumors and cells were evaluated using immunohistochemistry and liquid chromatography-mass spectrometry/mass spectrometry. An supF mutagenesis assay was used to determine H2O2-induced mutation rates of lung cancer cells with or without E6 expression. Results: Patients with E6-positive tumors had a greater frequency of EGFR mutations than those with E6-negative tumors (41% vs 20%; P =.006). Levels of 8-oxo-dG were correlated with EGFR mutations (36% vs 16%; P =.012). Two stable clones of E6-overexpressing H157 and CL-3 cells were established for the supF mutagenesis assay. The data indicated that the cells with high E6 overexpression had higher H2O2-induced SupF gene mutation rates compared with the cells that expressed lower levels of E6 and compared with vector control cells. Conclusions: HPV16/18 E6 may contribute in part to EGFR mutations in lung cancer, at least in the Taiwanese population.

AB - Background: Lung cancers in women, in nonsmokers, and in patients with adenocarcinoma from Asia have more prevalent mutations in the epidermal growth factor receptor (EGFR) gene than their counterparts. However, the etiology of EGFR mutations in this population remains unclear. The authors hypothesized that the human papillomavirus (HPV) type 16/18 (HPV16/18) E6 oncoprotein may contribute to EGFR mutations in Taiwanese patients with lung cancer. Methods: One hundred fifty-one tumors from patients with lung cancer were enrolled to determine HPV16/18 E6 and EGFR mutations using immunohistochemistry and direct sequencing, respectively. Levels of 8-oxo-7,8-dihydro-2′-deoxyguanosine (8-oxo-dG) in lung tumors and cells were evaluated using immunohistochemistry and liquid chromatography-mass spectrometry/mass spectrometry. An supF mutagenesis assay was used to determine H2O2-induced mutation rates of lung cancer cells with or without E6 expression. Results: Patients with E6-positive tumors had a greater frequency of EGFR mutations than those with E6-negative tumors (41% vs 20%; P =.006). Levels of 8-oxo-dG were correlated with EGFR mutations (36% vs 16%; P =.012). Two stable clones of E6-overexpressing H157 and CL-3 cells were established for the supF mutagenesis assay. The data indicated that the cells with high E6 overexpression had higher H2O2-induced SupF gene mutation rates compared with the cells that expressed lower levels of E6 and compared with vector control cells. Conclusions: HPV16/18 E6 may contribute in part to EGFR mutations in lung cancer, at least in the Taiwanese population.

KW - 8-dihydro-2& prime;-deoxyguanosine

KW - 8-oxo-7

KW - epidermal growth factor receptor

KW - human papillomavirus

KW - lung cancer

KW - mutation

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DO - 10.1002/cncr.28220

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