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| Status |
Public on Apr 29, 2010 |
| Title |
Investigating the epigenetic effects of a prototype smoke-derived carcinogen in human cells |
| Organism |
Homo sapiens |
| Experiment type |
Methylation profiling by genome tiling array
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| Summary |
Global loss of DNA methylation and locus/gene-specific gain of DNA methylation are two distinct hallmarks of carcinogenesis. Aberrant DNA methylation is implicated in smoking-related lung cancer. In this study, we have comprehensively investigated the modulation of DNA methylation consequent to chronic exposure to a prototype smoke-derived carcinogen, benzo[a]pyrene diol epoxide (B[a]PDE), in genomic regions of significance in lung cancer, in normal human cells. We have used a pulldown assay for enrichment of the CpG methylated fraction of cellular DNA combined with microarray platforms, followed by extensive validation through conventional bisulfite-based analysis. Here, we demonstrate strikingly similar patterns of DNA methylation in non-transformed B[a]PDE-treated cells vs control using high-throughput microarray-based DNA methylation profiling confirmed by conventional bisulfite-based DNA methylation analysis. The absence of aberrant DNA methylation in our model system within a timeframe that precedes cellular transformation suggests that following carcinogen exposure, other as yet unknown factors (secondary to carcinogen treatment) may help initiate global loss of DNA methylation and region-specific gain of DNA methylation, which can, in turn, contribute to lung cancer development. Unveiling the initiating events that cause aberrant DNA methylation in lung cancer has tremendous public health relevance, as it can help define future strategies for early detection and prevention of this highly lethal disease.
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| Overall design |
Methylated fragments in genomic DNA extracted from benzo[a]pyrene diol epoxide (B[a]PDE)-treated normal human fibroblasts versus control (solvent [dimethylsulfoxide (DMSO)-treated counterpart cells] were enriched with the MIRA assay and hybridized together with input genomic DNA to NimbleGen's whole genome tiling array.
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| Contributor(s) |
Bearatinia A, Wu X, Tommasi S, Kim S, Zhong X, Pfeifer GP |
| Citation(s) |
20485678 |
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| Submission date |
Apr 27, 2010 |
| Last update date |
Mar 22, 2012 |
| Contact name |
Xiwei Wu |
| E-mail(s) |
xwu@coh.org
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| Organization name |
City of Hope National Medical Center
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| Department |
Computational and Quantitative Medicine
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| Street address |
1500 E. Duarte Rd.
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| City |
Duarte |
| State/province |
CA |
| ZIP/Postal code |
91010 |
| Country |
USA |
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| Platforms (1) |
| GPL7587 |
NimbleGen HG18 Tiling Set Array 19 of 38 |
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| Samples (3) |
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| Relations |
| BioProject |
PRJNA125937 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE21532_RAW.tar |
57.1 Mb |
(http)(custom) |
TAR (of PAIR) |
| Processed data included within Sample table |
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