Aberrant methylation of the cyclin D2 promoter in primary small cell, nonsmall cell lung and breast cancers

Arvind Virmani, Asha Rathi, Shashank Heda, Kenji Sugio, Cheryl Lewis, Vijay Tonk, Takashi Takahashi, Jack A. Roth, John D. Minna, David M. Euhus, Adi F. Gazdar

Research output: Contribution to journalArticle

38 Scopus citations

Abstract

DNA methylation alteration of several genes contributes to human tumorigenesis. Cyclin D2, a member of the D-type cyclins, is implicated in cell cycle regulation and malignant transformation. In our study, we examined the methylation status of the cyclin D2 promoter in small cell lung cancer (SCLC), nonsmall cell lung cancer (NSCLC), breast tumors and tumor cell lines. We observed that aberrant methylation of cyclin D2 was present in 32 of 56 (57%) SCLC cell lines, 7 of 32 (22%) SCLC tumor tissues; 25 of 61 (47%) NSCLC cell lines, 19 of 48 (40%) NSCLC tumor tissues; 18 of 30 (60%) breast tumor cell lines and 19 of 63 (30%) breast tumor tissues. Methylation was more frequent in the tumor cell lines compared to the primary breast and SCLC tumors (p = 0.007 and p = 0.001, respectively). Methylation was rare in the control tissue samples; 0 of 12 peripheral blood lymphocytes; 0 of 12 buccal epithelial cells; 0 of 18 nonmalignant lung tissues and 3 of 28 (11%) nonmalignant breast tissues. Promoter methylation correlated with loss of transcript by reverse transcription PCR (RT-PCR) in 9 of 11 (6 lung, 5 breast) tumor cell lines tested. Two cell lines that were not methylated also lacked expression, suggesting that other mechanisms of inactivation may be involved. Expression was restored by treatment with the demethylating agent, 5 aza 2′ deoxycytidine, in all 9 methylated cell lines. Our results confirm earlier reports in breast cancer and indicate that aberrant methylation of cyclin D2 may contribute to the pathogenesis of the 2 major types of lung cancers.

Original languageEnglish (US)
Pages (from-to)341-345
Number of pages5
JournalInternational Journal of Cancer
Volume107
Issue number3
DOIs
StatePublished - Nov 10 2003

Keywords

  • Breast cancer
  • Cyclin D2
  • Methylation
  • Nonsmall cell lung cancer (NSCLC)
  • Small cell lung cancer (SCLC)

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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    Virmani, A., Rathi, A., Heda, S., Sugio, K., Lewis, C., Tonk, V., Takahashi, T., Roth, J. A., Minna, J. D., Euhus, D. M., & Gazdar, A. F. (2003). Aberrant methylation of the cyclin D2 promoter in primary small cell, nonsmall cell lung and breast cancers. International Journal of Cancer, 107(3), 341-345. https://doi.org/10.1002/ijc.11393