The presence of Merkel cell polyomavirus is associated with deregulated expression of BRAF and Bcl‐2 genes in non‐small cell lung cancer

• Published in: International journal of cancer Vol. 133; no. 3; pp. 604 - 611
• Main Authors: Lasithiotaki, I., Antoniou, K.M., Derdas, S.P., Sarchianaki, E., Symvoulakis, E.K., Psaraki, A., Spandidos, D.A., Stathopoulos, E.N., Siafakas, N.M., Sourvinos, G.
• Format: Journal Article
• Language: English
• Published: Hoboken, NJ Wiley-Blackwell 01.08.2013; Wiley Subscription Services, Inc
• Subjects: Aged; Bcl‐2; Biological and medical sciences; BK virus; BRAF; Cancer; Carcinoma, Non-Small-Cell Lung - genetics; Carcinoma, Non-Small-Cell Lung - virology; DNA, Viral - genetics; Female; Gene expression; Humans; JC virus; Lung cancer; Lung Neoplasms - genetics; Lung Neoplasms - virology; Male; Medical sciences; Merkel cell polyomavirus; Merkel cell polyomavirus - immunology; Merkel cell polyomavirus - isolation & purification; Middle Aged; Multiple tumors. Solid tumors. Tumors in childhood (general aspects); non‐small cell lung cancer; Phosphatidylethanolamine Binding Protein - genetics; Pneumology; Polymerase chain reaction; Polyomavirus; Polyomavirus Infections - genetics; Polyomavirus Infections - virology; Proto-Oncogene Proteins - genetics; Proto-Oncogene Proteins B-raf - genetics; Proto-Oncogene Proteins B-raf - metabolism; Proto-Oncogene Proteins c-bcl-2 - genetics; Proto-Oncogene Proteins c-bcl-2 - metabolism; Proto-Oncogene Proteins p21(ras); ras Proteins - genetics; RNA, Messenger - genetics; RNA, Messenger - metabolism; Smoking; Tumor Suppressor Protein p53 - genetics; Tumor Virus Infections - genetics; Tumors; Tumors of the respiratory system and mediastinum; Viruses; Bcl-2; non-small cell lung cancer; Lung disease; Respiratory disease; Lung cancer; BRAF; Malignant tumor; non-small cell lung carcinoma; Merkel cell polyomavirus; BRAF Gene; Association; Cancerology; C-Onc gene; Bronchus disease; Protooncogene; Cancer
• ISSN: 0020-7136; 1097-0215
• DOI: 10.1002/ijc.28062

Polyomaviruses such as BK virus (BKV), JC virus (JCV) and Merkel cell polyomavirus (MCPyV) are typically nononcogenic, although they have been detected in a variety of human neoplasms. The aim of our study was to determine the frequency of the most common polyomaviruses MCPyV, BKV and JCV as well as the gene expression profile of genes involved in oncogenesis including K‐ras, BRAF, RKIP, Bax, Bcl‐2, p53 and RB1 in a cohort of non‐small cell lung cancer (NSCLC) patients. Real‐time and nested polymerase chain reaction (PCR) were used to assess the presence of polyomaviruses DNA in tissue biopsies from 110 patients with primary NSCLC and 14 tissue specimens from macroscopically healthy sites of their lung. Real‐time PCR was also used to determine the mRNA expression of K‐ras, BRAF, RKIP, Bax, Bcl‐2, p53 and RB1 in selected samples. Results showed that ten NSCLC specimens were positive for the presence of MCPyV DNA (10/110, 9.1%), whereas no control sample was tested positive for the virus. The MCPyV‐positive samples were predominantly obtained from male smokers (9/10). BKV and JCV DNA were not detected either in lung tissues biopsies or the control specimens. Interestingly, gene expression analysis revealed increased mRNA and protein expression of BRAF gene in association with BRAF phosphorylation in the MCPyV‐positive samples, whereas Bcl‐2 gene expression was downregulated in the same type of samples. The detected MCPyV prevalence in NSCLC in combination with the deregulated expression of BRAF and Bcl‐2 genes suggests that these events are likely to contribute to the pathogenesis of NSCLC. What's new? An estimated one in five cancer cases worldwide are caused by infection, with the majority being caused by tumor viruses. The present study aimed to establish an association between human polyomavirus infection and non‐small cell lung cancer (NSCLC). The data implicate Merkel cell polyomavirus (MCPyV) in 9.1% of the cases in a cohort of 110 NSCLC patients. The expression profile of genes involved in oncogenesis also point to the deregulation of BRAF and Bcl‐2 in MCPyV‐positive NSCLC cells. These findings suggest the involvement of MCPyV in non‐small cell lung cancer through deregulation of BRAF and Bcl‐2.