Epigenetic silencing of human T (brachyury homologue) gene in non-small-cell lung cancer

Jong Chul Park, Young Kwang Chae, Choon Hee Son, Myoung Sook Kim, Juna Lee, Kimberly Ostrow, David Sidransky, Mohammad Obaidul Hoque, Chulso Moon

Research output: Contribution to journalArticle

Abstract

Early detection of lung cancer is challenging due to a lack of adequate biomarkers. To discover novel tumor suppressor genes (TSGs) silenced by aberrant promoter methylation, we analyzed the gene expression profiles of two lung adenocarcinoma cell lines using pharmacologic-unmasking and subsequent microarray-analysis. Among 617 genes upregulated, we selected 30 genes and investigated the methylation status of their promoters by bisulfite sequencing analysis. Aberrant methylation was detected in four genes (CRABP2, NOEY2, T, MAP2K3) in at least one lung adenocarcinoma cell lines. Furthermore, the T promoter was methylated in 60% of primary lung adenocarcinomas versus 13% of non-malignant lung tissues. Conversely, RT-PCR analysis revealed T expression was low in lung tumors, while high in normal tissues. In addition, no non-synonymous mutations related to gene silencing were found. While further analysis is warranted, our results suggest that T has the potential to be a novel candidate TSG in lung cancer.

Original languageEnglish (US)
Pages (from-to)221-226
Number of pages6
JournalBiochemical and Biophysical Research Communications
Volume365
Issue number2
DOIs
StatePublished - Jan 11 2008

Keywords

  • Brachyury homologue (mouse)
  • Lung adenocarcinoma
  • Non-small-cell lung cancer
  • Promoter hypermethylation
  • T gene
  • Tumor suppressor gene

ASJC Scopus subject areas

  • Biophysics
  • Biochemistry
  • Molecular Biology
  • Cell Biology

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