Aberrant methylation profile of human malignant mesotheliomas and its relationship to SV40 infection

Makoto Suzuki, Shinichi Toyooka, Narayan Shivapurkar, Hisayuki Shigematsu, Kuniharu Miyajima, Takao Takahashi, Victor Stastny, Andrea L. Zern, Takehiko Fujisawa, Harvey I. Pass, Michele Carbone, Adi F. Gazdar

Research output: Contribution to journalArticle

68 Scopus citations

Abstract

Malignant mesothelioma (MM) is associated with asbestos exposure and the presence of SV40 viral sequences. Recently, we reported that SV40 infection of human mesothelial cells (HM) causes aberrant methylation of the tumor suppressor gene (TSG) RASSF1A. We investigated methylation of 12 genes by methylation-specific PCR in 63 MMs, six MM cell lines, and two foci of SV40-infected HM. Methylation percentages of the tested genes ranged from 3 to 65%. The frequencies of HPP1, RASSF1A, Cyclin D2, and RRAD methylation, and the value of the methylation index, were significantly higher in SV40 sequence-positive MMs than in SV40-negative MMs. Methylation of TMS1 and HIC-1 was associated with shortened survival. SV40-infected HM showed progressive aberrant methylation of seven genes (RASSF1A, HPP1, DcR1, TMS1, CRBP1, HIC-1, and RRAD) during serial passage. Our results demonstrate a relationship between SV40 and methylation of multiple genes in MM, indicating that the virus plays a role in the pathogenesis of MM.

Original languageEnglish (US)
Pages (from-to)1302-1308
Number of pages7
JournalOncogene
Volume24
Issue number7
DOIs
StatePublished - Feb 10 2005

Keywords

  • Malignant mesothelioma
  • Methylation
  • SV40

ASJC Scopus subject areas

  • Molecular Biology
  • Genetics
  • Cancer Research

Fingerprint Dive into the research topics of 'Aberrant methylation profile of human malignant mesotheliomas and its relationship to SV40 infection'. Together they form a unique fingerprint.

  • Cite this

    Suzuki, M., Toyooka, S., Shivapurkar, N., Shigematsu, H., Miyajima, K., Takahashi, T., Stastny, V., Zern, A. L., Fujisawa, T., Pass, H. I., Carbone, M., & Gazdar, A. F. (2005). Aberrant methylation profile of human malignant mesotheliomas and its relationship to SV40 infection. Oncogene, 24(7), 1302-1308. https://doi.org/10.1038/sj.onc.1208263