title: Epigenetic silencing of human T (brachyury homologue) gene in non-small-cell lung cancer.
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.
authors.affiliation: Department of Otolaryngology-Head and Neck Surgery, Johns Hopkins University, 1550 Orleans Street, Baltimore, MD 21231, USA.
authors.forename: Jong Chul
authors.initials: JC
authors.lastname: Park
authors.forename: Young Kwang
authors.initials: YK
authors.lastname: Chae
authors.forename: Choon Hee
authors.initials: CH
authors.lastname: Son
authors.forename: Myoung Sook
authors.initials: MS
authors.lastname: Kim
authors.forename: Juna
authors.initials: J
authors.lastname: Lee
authors.forename: Kimberly
authors.initials: K
authors.lastname: Ostrow
authors.forename: David
authors.initials: D
authors.lastname: Sidransky
authors.forename: Mohammad Obaidul
authors.initials: MO
authors.lastname: Hoque
authors.forename: Chulso
authors.initials: C
authors.lastname: Moon
mesh_terms: D002289:Carcinoma, Non-Small-Cell Lung / Q000235:genetics* / Q000378:metabolism*; D045744:Cell Line, Tumor; D044127:Epigenesis, Genetic / Q000235:genetics*; D005326:Fetal Proteins / Q000235:genetics* / Q000378:metabolism*; D020868:Gene Silencing; D018390:Gene Targeting / Q000379:methods*; D015316:Genetic Therapy / Q000379:methods*; D006801:Humans; D020825:T-Box Domain Proteins / Q000235:genetics* / Q000378:metabolism*; D000098908:Brachyury Protein
chemical_list: D005326:Fetal Proteins; D020825:T-Box Domain Proteins; D000098908:Brachyury Protein