Aberrant methylation of TMS1 in small cell, non small cell lung cancer and breast cancer

Arvind Virmani, Asha Rathi, Kenji Sugio, Ubaradka G. Sathyanarayana, Shinichi Toyooka, Frank C. Kischel, Vijay Tonk, Asha Padar, Takashi Takahashi, Jack A. Roth, David M Euhus, John D. Minna, Adi F. Gazdar

Research output: Contribution to journalArticle

Abstract

TMS1 (target of methylation-induced silencing) is a CpG island-associated gene that functions in the regulation of apoptosis and encodes a caspase recruitment domain, a recently described motif found in apoptotic signaling molecules. Recent evidence suggests that silencing of genes in the apoptotic pathway contribute to human carcinogenesis. We examined the DNA methylation status of the TMS1 promoter in lung and breast tumor tissues, tumor cell lines and nonmalignant tissues by methylation-specific polymerase chain reaction (MSP) and its mRNA expression by reverse transcription PCR. Aberrant methylation of TMS1 was present in 70% (40 of 57) of small cell lung cancer (SCLC) cell lines and 41% (13 of 32) of SCLC tumor tissues, 48% (29 of 61) of non small cell lung cancer (NSCLC) cell lines and 40% (28 of 70) of NSCLC tumor tissues and 46% (12 of 26) of breast cancer cell lines and 32% (20 of 63) of breast tumor tissues. Methylation was absent in the peripheral blood lymphocytes and buccal epithelium from healthy volunteers, as well as in nonmalignant lung tissues and was rare in nonmalignant breast tissues 7% (2 of 30). DNA methylation was confirmed by sequence analysis and the methylation status correlated inversely with TMS1 RNA expression in 18 cell lines tested. RNA expression was restored by treatment with the demethylating agent 5-aza-2′-deoxycytidine, in 4 of 4 methylated cell lines that lacked the TMS1 transcript. Our results suggest that methylation of TMS1 may play a role in the pathogenesis of small cell and non small lung and breast cancers.

Original languageEnglish (US)
Pages (from-to)198-204
Number of pages7
JournalInternational Journal of Cancer
Volume106
Issue number2
DOIs
StatePublished - Aug 20 2003
Externally publishedYes

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Non-Small Cell Lung Carcinoma
Methylation
Breast Neoplasms
Cell Line
decitabine
Small Cell Lung Carcinoma
DNA Methylation
RNA
Polymerase Chain Reaction
Lung
CpG Islands
Cheek
Gene Silencing
Tumor Cell Line
Reverse Transcription
Sequence Analysis
Lung Neoplasms
Neoplasms
Healthy Volunteers
Carcinogenesis

Keywords

  • Breast cancer
  • Methylation
  • NSCLC
  • SCLC
  • TMS1

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Virmani, A., Rathi, A., Sugio, K., Sathyanarayana, U. G., Toyooka, S., Kischel, F. C., ... Gazdar, A. F. (2003). Aberrant methylation of TMS1 in small cell, non small cell lung cancer and breast cancer. International Journal of Cancer, 106(2), 198-204. https://doi.org/10.1002/ijc.11206

Aberrant methylation of TMS1 in small cell, non small cell lung cancer and breast cancer. / Virmani, Arvind; Rathi, Asha; Sugio, Kenji; Sathyanarayana, Ubaradka G.; Toyooka, Shinichi; Kischel, Frank C.; Tonk, Vijay; Padar, Asha; Takahashi, Takashi; Roth, Jack A.; Euhus, David M; Minna, John D.; Gazdar, Adi F.

In: International Journal of Cancer, Vol. 106, No. 2, 20.08.2003, p. 198-204.

Research output: Contribution to journalArticle

Virmani, A, Rathi, A, Sugio, K, Sathyanarayana, UG, Toyooka, S, Kischel, FC, Tonk, V, Padar, A, Takahashi, T, Roth, JA, Euhus, DM, Minna, JD & Gazdar, AF 2003, 'Aberrant methylation of TMS1 in small cell, non small cell lung cancer and breast cancer', International Journal of Cancer, vol. 106, no. 2, pp. 198-204. https://doi.org/10.1002/ijc.11206
Virmani A, Rathi A, Sugio K, Sathyanarayana UG, Toyooka S, Kischel FC et al. Aberrant methylation of TMS1 in small cell, non small cell lung cancer and breast cancer. International Journal of Cancer. 2003 Aug 20;106(2):198-204. https://doi.org/10.1002/ijc.11206
Virmani, Arvind ; Rathi, Asha ; Sugio, Kenji ; Sathyanarayana, Ubaradka G. ; Toyooka, Shinichi ; Kischel, Frank C. ; Tonk, Vijay ; Padar, Asha ; Takahashi, Takashi ; Roth, Jack A. ; Euhus, David M ; Minna, John D. ; Gazdar, Adi F. / Aberrant methylation of TMS1 in small cell, non small cell lung cancer and breast cancer. In: International Journal of Cancer. 2003 ; Vol. 106, No. 2. pp. 198-204.
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AU - Rathi, Asha

AU - Sugio, Kenji

AU - Sathyanarayana, Ubaradka G.

AU - Toyooka, Shinichi

AU - Kischel, Frank C.

AU - Tonk, Vijay

AU - Padar, Asha

AU - Takahashi, Takashi

AU - Roth, Jack A.

AU - Euhus, David M

AU - Minna, John D.

AU - Gazdar, Adi F.

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N2 - TMS1 (target of methylation-induced silencing) is a CpG island-associated gene that functions in the regulation of apoptosis and encodes a caspase recruitment domain, a recently described motif found in apoptotic signaling molecules. Recent evidence suggests that silencing of genes in the apoptotic pathway contribute to human carcinogenesis. We examined the DNA methylation status of the TMS1 promoter in lung and breast tumor tissues, tumor cell lines and nonmalignant tissues by methylation-specific polymerase chain reaction (MSP) and its mRNA expression by reverse transcription PCR. Aberrant methylation of TMS1 was present in 70% (40 of 57) of small cell lung cancer (SCLC) cell lines and 41% (13 of 32) of SCLC tumor tissues, 48% (29 of 61) of non small cell lung cancer (NSCLC) cell lines and 40% (28 of 70) of NSCLC tumor tissues and 46% (12 of 26) of breast cancer cell lines and 32% (20 of 63) of breast tumor tissues. Methylation was absent in the peripheral blood lymphocytes and buccal epithelium from healthy volunteers, as well as in nonmalignant lung tissues and was rare in nonmalignant breast tissues 7% (2 of 30). DNA methylation was confirmed by sequence analysis and the methylation status correlated inversely with TMS1 RNA expression in 18 cell lines tested. RNA expression was restored by treatment with the demethylating agent 5-aza-2′-deoxycytidine, in 4 of 4 methylated cell lines that lacked the TMS1 transcript. Our results suggest that methylation of TMS1 may play a role in the pathogenesis of small cell and non small lung and breast cancers.

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