Association of epidermal growth factor receptor mutations with human papillomavirus 16/18 E6 oncoprotein expression in non–small cell lung cancer. Issue 18 (24th June 2013)

• Record Type: Journal Article
• Authors: Tung, Min‐Che; Wu, Heng‐Hsiung; Cheng, Ya‐Wen; Wang, Lee; Chen, Chih‐Yi; Yeh, Sauh‐Der; Wu, Tzu‐Chin; Lee, Huei
• Is Part Of: Cancer. Volume 119:Issue 18(2013)
• Page Start: 3367
• Page End: 3376
• Publication Date: 2013-06-24
• Subjects: Cancer -- Periodicals; Cancer -- Cytopathology -- Periodicals; 616.99405
• DOI: 10.1002/cncr.28220
• Languages: English
• ISSNs: 0008-543X

Abstract

<abstract abstract-type="main"> <title> <x xml:space="preserve">Abstract</x> </title> <sec id="cncr28220-sec-0001" sec-type="section"> <title>BACKGROUND</title> <p>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.</p> </sec> <sec id="cncr28220-sec-0002" sec-type="section"> <title>METHODS</title> <p>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 <italic>supF</italic> mutagenesis assay was used to determine H<sub>2</sub>O<sub>2</sub>‐induced mutation rates of lung cancer cells with or without E6 expression.</p> </sec> <sec id="cncr28220-sec-0003" sec-type="section"> <title>RESULTS</title> <p>Patients with E6‐positive tumors had a greater frequency of EGFR mutations than those with E6‐negative tumors (41% vs 20%; <italic>P</italic> = .006). Levels of 8‐oxo‐dG were correlated with EGFR mutations (36% vs 16%; <italic>P</italic> = .012). Two stable clones of E6‐overexpressing H157 and CL‐3 cells were established for the <italic>supF</italic> mutagenesis assay. The data indicated that the cells with high E6 overexpression had higher H<sub>2</sub>O<sub>2</sub>‐induced <italic>SupF</italic> gene mutation rates compared with the cells that expressed lower levels of E6 and compared with vector control cells.</p> </sec> <sec id="cncr28220-sec-0004" sec-type="section"> <title>CONCLUSIONS</title> <p>HPV16/18 E6 may contribute in part to EGFR mutations in lung cancer, at least in the Taiwanese population. <bold><italic>Cancer</italic> 2013;119:3367–76</bold>. © <italic>2013 American Cancer Society</italic>.</p> </sec> </abstract>