Frequent hypermethylation of RASSF1A tumour suppressor gene promoter and presence of Merkel cell polyomavirus in small cell lung cancer

• Published in: European Journal of Cancer Vol. 45; no. 12; pp. 2207 - 2211
• Main Authors: Helmbold, Peter, Lahtz, Christoph, Herpel, Esther, Schnabel, Philipp A, Dammann, Reinhard H
• Format: Journal Article
• Language: English
• Published: Kidlington Elsevier Ltd 01-08-2009; Elsevier
• Subjects: Biological and medical sciences; Blood; Carcinoma, Merkel Cell - genetics; Carcinoma, Merkel Cell - virology; DNA methylation; DNA Methylation - genetics; DNA, Viral; Female; Genes, p16 - physiology; Hematology, Oncology and Palliative Medicine; Humans; Lung Neoplasms - genetics; Lung Neoplasms - virology; Male; Medical sciences; Merkel cell polyomavirus; p16; Pharmacology. Drug treatments; Polyomavirus; Polyomavirus Infections - genetics; Polyomavirus Infections - virology; RASSF1; Simian virus 40 - genetics; Skin Neoplasms - genetics; Skin Neoplasms - virology; Small cell lung cancer; SV40; Tumor Suppressor Proteins - genetics; Tumor Suppressor Proteins - metabolism; Tumor Virus Infections - genetics; Tumor Virus Infections - virology; Tumors; Tumour suppressor; Small cell lung cancer; RASSF1; p16; DNA methylation; SV40; Tumour suppressor; Merkel cell polyomavirus; Lung cancer; Bonchopulmonary small cell carcinoma; Merkel cell; Papovaviridae; CDKN2 gene; Promoter; Cancerology; Bronchus disease; Tumor suppressor gene; Lung disease; Respiratory disease; Polyomavirus; Malignant tumor; Suppressor gene; Simian virus 40; Infection; Virus; DNA; Viral disease; Frequency; Methylation; Cancer
• ISSN: 0959-8049; 1879-0852; 1359-6349
• DOI: 10.1016/j.ejca.2009.04.038

Abstract In small cell lung cancer (SCLC), hypermethylation of the tumour suppressor Ras association domain family 1A ( RASSF1A ) is frequent. It is associated with SV40 polyomaviral infection in other tumours. Merkel cell polyomavirus (MCPyV) infection has been reported in Merkel cell carcinoma (MCC), a neuroendocrine carcinoma with biological similarity to SCLC. In our study, we investigated polyomavirus infection (SV40 and MCPyV) and promoter hypermethylation of the tumour suppressors RASSF1A and p16 in 18 SCLCs (14 primaries and 4 regional lymph node metastases) and 18 blood control samples. MCPyV was found in 39% (7 of 18) of the tumour tissues but not observed in controls. SV40 was not observed in the tumour tissue. RASSF1A promoter hypermethylation (94%; 17 of 18) was more frequent compared to p16 methylation (56%, 10 of 18). We found no significant correlation between RASSF1A or p16 promoter hypermethylation and infection with the investigated polyoma viruses. Our results show a high frequency of hypermethylation of the RASSF1A promoter and occurrence of MCPyV infection in the tumour tissue of SCLC. These events may contribute to the pathogenesis of SCLC.