Epigenetic silencing of human T (brachyury homologue) gene in non-small-cell lung cancer.
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.
Park
Jong Chul
JC
Department of Otolaryngology-Head and Neck Surgery, Johns Hopkins University, 1550 Orleans Street, Baltimore, MD 21231, USA.
Chae
Young Kwang
YK
Son
Choon Hee
CH
Kim
Myoung Sook
MS
Lee
Juna
J
Ostrow
Kimberly
K
Sidransky
David
D
Hoque
Mohammad Obaidul
MO
Moon
Chulso
C
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
D005326:Fetal Proteins; D020825:T-Box Domain Proteins; D000098908:Brachyury Protein