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

Oncogene volume 24, pages 1302–1308 (2005)Cite this article

A Retraction to this article was published on 22 May 2014

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.

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Abbreviations

MM:

malignant pleural mesothelioma

HM:

human mesothelial cells

SV40:

simian virus 40

TSG:

tumor suppressor gene

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Acknowledgements

This work was supported by grants from the UT Specialized Program of Research Excellence in Lung Cancer (P50CA70907) and Early Detection Research Network (5U01CA8497102), National Cancer Institute. Michele Carbone's work was supported by grants RO-1 CA92657 from the Charlotte Geyer Foundation, and by RPG-99-238-01-CAN from the American Cancer Society.

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Author notes

  1. Makoto Suzuki and Shinichi Toyooka: These two authors contributed equally to this work

Authors and Affiliations

  1. Hamon Center for Therapeutic Oncology Research, University of Texas Southwestern Medical Center, Dallas, TX, 75390, USA

    Makoto Suzuki, Shinichi Toyooka, Narayan Shivapurkar, Hisayuki Shigematsu, Kuniharu Miyajima, Takao Takahashi, Victor Stastny, Andrea L Zern & Adi F Gazdar

  2. Department of Thoracic Surgery, Graduate School of Medicine, Chiba University, Chiba, 2608670, Japan

    Makoto Suzuki & Takehiko Fujisawa

  3. Department of Pathology, University of Texas Southwestern Medical Center, Dallas, TX, 75390, USA

    Narayan Shivapurkar & Adi F Gazdar

  4. Department of Thoracic Surgery, Karamanos Cancer Center, Detroit, MI, 48201, USA

    Harvey I Pass

  5. Department of Pathology, Cardinal Bernardin Cancer Center, Loyola University Chicago, Maywood, IL, 60153, USA

    Michele Carbone

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  1. Makoto Suzuki
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Correspondence to Adi F Gazdar.

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Suzuki, M., Toyooka, S., Shivapurkar, N. et al. Aberrant methylation profile of human malignant mesotheliomas and its relationship to SV40 infection. Oncogene 24, 1302–1308 (2005). https://doi.org/10.1038/sj.onc.1208263

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