RETRACTED: Aberrant methylation profile of human malignant mesotheliomas and its relationship to SV40 infection (Retracted Article)

被引:60
作者
Suzuki, M
Toyooka, S
Shivapurkar, N
Shigematsu, H
Miyajima, K
Takahashi, T
Stastny, V
Zern, AL
Fujisawa, T
Pass, HI
Carbone, M
Gazdar, AF
机构
[1] Univ Texas, SW Med Ctr, Hamon Ctr Therapeut Oncol Res, Dallas, TX 75390 USA
[2] Chiba Univ, Grad Sch Med, Dept Thorac Surg, Chiba 2608670, Japan
[3] Univ Texas, SW Med Ctr, Dept Pathol, Dallas, TX 75390 USA
[4] Karamanos Canc Ctr, Dept Thorac Surg, Detroit, MI 48201 USA
[5] Loyola Univ, Cardinal Bernardin Canc Ctr, Dept Pathol, Maywood, IL 60153 USA
关键词
methylation; malignant mesothelioma; SV40;
D O I
10.1038/sj.onc.1208263
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
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.
引用
收藏
页码:1302 / 1308
页数:7
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