Global methylation profiling of lung cancer identifies novel methylated genes.
Epigenetic changes, including DNA methylation, are a common finding in cancer. In lung cancers methylation of cytosine residues may affect tumor initiation and progression in several ways, including the silencing of tumor suppressor genes through promoter methylation and by providing the targets for adduct formation of polycyclic aromatic hydrocarbons present in combustion products of cigarette smoke. Although the importance of aberrant DNA methylation is well established, the extent of DNA methylation in lung cancers has never been determined. Restriction landmark genomic scanning (RLGS) is a highly reproducible two-dimensional gel electrophoresis that allows the determination of the methylation status of up to 2000 promoter sequences in a single gel. We selected 1184 CpG islands for RLGS analysis and determined their methylation status in 16 primary non-small cell lung cancers. Some tumors did not show methylation whereas others showed up to 5.3% methylation in all CpG islands of the profile. Cloning of 21 methylated loci identified 11 genes and 6 ESTs. We demonstrate that methylation is part of the silencing process of BMP3B in primary tumors and lung cancer cell lines.
Dai
Z
Z
Division of Human Cancer Genetics, Department of Molecular Virology, Immunology and Medical Genetics, The Ohio State University, 420 West 12th Avenue, Columbus, OH 43210, USA.
Lakshmanan
R R
RR
Zhu
W G
WG
Smiraglia
D J
DJ
Rush
L J
LJ
Frühwald
M C
MC
Brena
R M
RM
Li
B
B
Wright
F A
FA
Ross
P
P
Otterson
G A
GA
Plass
C
C
D000368:Aged; D000369:Aged, 80 and over; D018287:Carcinoma, Large Cell / Q000235:genetics / Q000378:metabolism; D002289:Carcinoma, Non-Small-Cell Lung / Q000235:genetics* / Q000378:metabolism; D018899:CpG Islands; D019175:DNA Methylation; D004273:DNA, Neoplasm / Q000032:analysis*; D015536:Down-Regulation; D005260:Female; D020869:Gene Expression Profiling; D020868:Gene Silencing; D016147:Genes, Tumor Suppressor; D006801:Humans; D008175:Lung Neoplasms / Q000235:genetics* / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D009363:Neoplasm Proteins / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D017422:Sequence Analysis, DNA; D014407:Tumor Cells, Cultured
D004273:DNA, Neoplasm; D009363:Neoplasm Proteins