Detection and expression of human papillomavirus oncogenes in non-small cell lung cancer.
Human papillomavirus (HPV) has been found in lung cancer cases with variable frequency. In the present study, we analysed a series of 38 patients with non-small cell lung cancer (NSCLC) (21 paraffin-embedded archival samples and 17 fresh surgical specimens) for the presence of E6 and E7 oncogenes of HPV16, 18 and 31. Eight of the tumours were positive (21%): six HPV16, one HPV16+18, and one HPV31. The normal tissue surrounding the HPV-positive tumour was negative for the presence of the virus. Sequencing analysis of URR, of HPV16, which was the most frequently found HPV type in our cases, showed an adenosine deletion at nucleotide 7861 (E2-binding site) in four out of six patients. Sequencing of the entire E6 and E7 genes of HPV16 showed a T to G transition at nucleotide position 350 of E6, in all examined cases. This mutation is associated to the European variant of HPV16. Analysis of E6 and E7 transcripts was performed on the six fresh surgical specimens infected by HPV16. Our study showed that all of the tumours investigated, except one, contained E6 and E7 transcripts. Only in one case could we identify an unspliced form of the E6 transcript. Our results strengthen the relationship between HPV and NSCLC and support the hypothesis that HPV infection could play a role in bronchial carcinogenesis.
Ciotti
Marco
M
Laboratory of Clinical Microbiology and Virology, University of Tor Vergata, Rome, Italy. marco.ciotti@ptvonline.it
Giuliani
Laura
L
Ambrogi
Vincenzo
V
Ronci
Corrado
C
Benedetto
Arrigo
A
Mineo
Tommaso C
TC
Syrjänen
Kari
K
Favalli
Cartesio
C
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002289:Carcinoma, Non-Small-Cell Lung / Q000235:genetics* / Q000821:virology*; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D015967:Gene Expression Regulation, Viral; D005814:Genes, Viral; D006801:Humans; D008175:Lung Neoplasms / Q000235:genetics* / Q000821:virology*; D008297:Male; D008875:Middle Aged; D009856:Oncogene Proteins, Viral / Q000235:genetics; D027383:Papillomaviridae / Q000235:genetics*; D050725:Papillomavirus E7 Proteins; D012097:Repressor Proteins / Q000235:genetics
C068651:E6 protein, Human papillomavirus type 16; D009856:Oncogene Proteins, Viral; D050725:Papillomavirus E7 Proteins; D012097:Repressor Proteins; C059731:oncogene protein E7, Human papillomavirus type 16