DNA methylation profiles of lung tumors

Shinichi Toyooka, Kiyomi O. Toyooka, Riichiroh Maruyama, Arvind K. Virmani, Luc Girard, Kuniharu Miyajima, Kenichi Harada, Yutaka Ariyoshi, Takashi Takahashi, Kenji Sugio, Elisabeth Brambilla, Michel Gilcrease, John D. Minna, Adi F. Gazdar

Research output: Contribution to journalArticle

220 Citations (Scopus)

Abstract

Aberrant methylation of CpG islands in promoter regions of tumor cells is one of the major mechanisms for silencing of tumor suppressor genes. We determined the frequency of aberrant promoter methylation of the p16, adenomatous polyposis coli (APC), H-cadherin (CDH13), glutathione S-transferase P1 (GSTP1), O6-methylguanine-DNA-methyltransferase (MGMT), retinoic acid receptor β-2 (RARβ), E-cadherin (CDH1), and RAS association domain family 1A (RASSF1A) genes in 198 tumors consisting of small cell lung cancers [SCLCs (n = 43)], non-small cell lung cancers [NSCLCs (n = 115)], and bronchial carcinoids (n = 40). The profile of methylated genes in the two neuroendocrine tumors (SCLC and carcinoids) were very different from that of NSCLC. However, whereas the overall pattern of aberrant methylation of carcinoids was similar to that of SCLC, carcinoids had lower frequencies of methylation for some of the genes tested. There were also significant differences in the methylation profiles between the two major types of NSCLC, adenocarcinoma and squamous cell carcinoma. We performed cluster analysis and found that SCLCs clustered with other SCLCs and carcinoids but not with NSCLCs, whereas the NSCLCs tended to cluster together. Within NSCLCs, adenocarcinomas and squamous cell carcinomas clustered with their respective histological types. Finally, we compared the methylation profiles of SCLC and NSCLC tumors and their respective cell lines (n = 44). In general, methylation frequencies were higher in tumor cell lines, but these differences were seldom significant. Thus, tumor cell lines appear to be suitable models to study aberrant DNA methylation. We conclude that SCLC, carcinoids, squamous cell carcinomas, and adenocarcinomas of the lung have unique profiles of aberrant methylation. Our findings should help us understand differences in the pathogenetic mechanisms of lung cancers.

Original languageEnglish (US)
Pages (from-to)61-67
Number of pages7
JournalMolecular Cancer Therapeutics
Volume1
Issue number1
StatePublished - Nov 2001

Fingerprint

DNA Methylation
Methylation
Carcinoid Tumor
Lung
Neoplasms
Squamous Cell Carcinoma
Tumor Cell Line
Adenocarcinoma
Genes
Retinoic Acid Receptors
CpG Islands
Adenomatous Polyposis Coli
Neuroendocrine Tumors
Small Cell Lung Carcinoma
Methyltransferases
Cadherins
Glutathione Transferase
Tumor Suppressor Genes
Genetic Promoter Regions
Non-Small Cell Lung Carcinoma

ASJC Scopus subject areas

  • Oncology
  • Cancer Research
  • Drug Discovery
  • Pharmacology

Cite this

Toyooka, S., Toyooka, K. O., Maruyama, R., Virmani, A. K., Girard, L., Miyajima, K., ... Gazdar, A. F. (2001). DNA methylation profiles of lung tumors. Molecular Cancer Therapeutics, 1(1), 61-67.

DNA methylation profiles of lung tumors. / Toyooka, Shinichi; Toyooka, Kiyomi O.; Maruyama, Riichiroh; Virmani, Arvind K.; Girard, Luc; Miyajima, Kuniharu; Harada, Kenichi; Ariyoshi, Yutaka; Takahashi, Takashi; Sugio, Kenji; Brambilla, Elisabeth; Gilcrease, Michel; Minna, John D.; Gazdar, Adi F.

In: Molecular Cancer Therapeutics, Vol. 1, No. 1, 11.2001, p. 61-67.

Research output: Contribution to journalArticle

Toyooka, S, Toyooka, KO, Maruyama, R, Virmani, AK, Girard, L, Miyajima, K, Harada, K, Ariyoshi, Y, Takahashi, T, Sugio, K, Brambilla, E, Gilcrease, M, Minna, JD & Gazdar, AF 2001, 'DNA methylation profiles of lung tumors', Molecular Cancer Therapeutics, vol. 1, no. 1, pp. 61-67.
Toyooka S, Toyooka KO, Maruyama R, Virmani AK, Girard L, Miyajima K et al. DNA methylation profiles of lung tumors. Molecular Cancer Therapeutics. 2001 Nov;1(1):61-67.
Toyooka, Shinichi ; Toyooka, Kiyomi O. ; Maruyama, Riichiroh ; Virmani, Arvind K. ; Girard, Luc ; Miyajima, Kuniharu ; Harada, Kenichi ; Ariyoshi, Yutaka ; Takahashi, Takashi ; Sugio, Kenji ; Brambilla, Elisabeth ; Gilcrease, Michel ; Minna, John D. ; Gazdar, Adi F. / DNA methylation profiles of lung tumors. In: Molecular Cancer Therapeutics. 2001 ; Vol. 1, No. 1. pp. 61-67.
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