Detection of group C adenovirus DNA in small-cell lung cancer with the nested polymerase chain reaction

Abstract

Group C adenovirus is latent in human tissues and can malignantly transform cells. The purpose of this study was to investigate the association between this virus and lung cancer. We investigated latent adenoviral infection using the nested polymerase chain reaction and in situ hybridization in transbronchial biopsy specimens from patients with small-cell lung cancer and non-small-cell lung cancer. The polymerase chain reaction was performed on DNA extracts with two sets of primers directed at a 261-base-pair target sequence of the E1A region of the adenoviral genome. In situ hybridization was performed on histological sections using DNA representing the entire adenovirus type 5 genome. E1A target DNA was present in 11 (31%) of 35 cases of small-cell lung cancer but in none of the 40 cases of non-small-cell lung cancer (P < 0.01). Of the 11 cases found positive by PCR, 8 were positive for adenovirus DNA by in situ hybridization. Adenovirus was prominent in tumor cells in 5 of the 8 cases, and in normal epithelial cells in the 3 remaining cases. Adenovirus DNA was not detected by in situ hybridization in specimens in which E1A DNA was not detected by the polymerase chain reaction. Small-cell lung cancer has mutations or deletions in the p53 and retinoblastoma genes more frequently than are found in non-small-cell lung cancer. Therefore, we speculate that adenovirus infection might participate in the pathogenesis of SCLC by producing mutation in these genes, rather than by inhibiting the function of these proteins.

Comparative Sequence Analysis of the Hexon Gene in the Entire Spectrum of Human Adenovirus Serotypes: Phylogenetic, Taxonomic, and Clinical Implications

“…Indeed, certain AdV types are known to cause specific diseases in immunocompetent individuals, such as the serotypes E04 and B07, which cause acute respiratory infections (6), or serotype D08, which is known to cause highly contagious keratoconjunctivitis (1). By contrast, relatively little is known about the relevance of many other AdV serotypes with regard to their infectious potential and the possible oncogenic properties in humans (15,17).…”

Prevalence and Quantitation of Species C Adenovirus DNA in Human Mucosal Lymphocytes

“…The association between adenovirus and cigarette smoking in lung pathogenesis goes even further. PCR screening detects species C adenovirus DNA in one-third of small-cell lung cancers, a disease found virtually only in tobacco smokers (19). Although it is clear that even normal children and adults carry adenovirus DNA in their respiratory tract, adenovirus levels are not increased in all respiratory tract diseases.…”

“…Although it is clear that even normal children and adults carry adenovirus DNA in their respiratory tract, adenovirus levels are not increased in all respiratory tract diseases. The level of adenovirus DNA is not elevated in adenocarcinoma or squamous cell carcinoma of the lung (19), idiopathic pulmonary fibrosis (20), cystic fibrosis (9), or chronic sinusitis (27). Thus, elucidation of the mechanisms by which species C adenoviruses persist in mucosal lymphoid tissues may inform attempts to identify their role in chronic inflammatory diseases.…”

Experimental infections of humans with wild-type adenoviruses and with replication-competent adenovirus vectors: replication, safety, and transmission

“…58 Ad DNA was present in tumor tissue from patients with small-cell lung carcinoma (31%; 11 out of 35 cases) but not nonsmall-cell lung carcinoma (0%; out of 0 of 40). 59 A variable proportion of lung tissue specimens from patients with idiopathic pulmonary fibrosis, interstitial pneumonia associated with collagen vascular disease, and sarcoidosis were positive for Ad DNA, although there appeared to be no causal relationship. 60 Overall, the studies cited above suggest that Ad may persist and/or become latent in the tonsils, adenoids, or lungs of infected individuals.…”