title: Aberrant methylation profile of human malignant mesotheliomas and its relationship to SV40 infection.
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.
authors.affiliation: Hamon Center for Therapeutic Oncology Research, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA.
authors.forename: Makoto
authors.initials: M
authors.lastname: Suzuki
authors.forename: Shinichi
authors.initials: S
authors.lastname: Toyooka
authors.forename: Narayan
authors.initials: N
authors.lastname: Shivapurkar
authors.forename: Hisayuki
authors.initials: H
authors.lastname: Shigematsu
authors.forename: Kuniharu
authors.initials: K
authors.lastname: Miyajima
authors.forename: Takao
authors.initials: T
authors.lastname: Takahashi
authors.forename: Victor
authors.initials: V
authors.lastname: Stastny
authors.forename: Andrea L
authors.initials: AL
authors.lastname: Zern
authors.forename: Takehiko
authors.initials: T
authors.lastname: Fujisawa
authors.forename: Harvey I
authors.initials: HI
authors.lastname: Pass
authors.forename: Michele
authors.initials: M
authors.lastname: Carbone
authors.forename: Adi F
authors.initials: AF
authors.lastname: Gazdar
mesh_terms: D045744:Cell Line, Tumor; D019175:DNA Methylation; D004848:Epithelium / Q000378:metabolism / Q000821:virology; D016147:Genes, Tumor Suppressor; D006801:Humans; D008654:Mesothelioma / Q000235:genetics* / Q000378:metabolism / Q000821:virology*; D027601:Polyomavirus Infections / Q000235:genetics* / Q000378:metabolism; D013539:Simian virus 40; D014412:Tumor Virus Infections / Q000235:genetics* / Q000378:metabolism