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GEO help: Mouse over screen elements for information. |
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| Status |
Public on Feb 07, 2018 |
| Title |
Epigenome-wide analysis of DNA methylation in lung tissue shows concordance with blood studies and identifies tobacco smoke-inducible enhancers |
| Organism |
Homo sapiens |
| Experiment type |
Expression profiling by high throughput sequencing
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| Summary |
Smoking-associated DNA hypomethylation has been observed in blood cells and linked to lung cancer risk. However, its cause and mechanistic relationship to lung cancer remain unclear. We studied the association between tobacco smoking and epigenome-wide methylation in non-tumor lung (NTL) tissue from 237 lung cancer cases in the Environment And Genetics in Lung cancer Etiology study, using the Infinium HumanMethylation450 BeadChip. We identified seven smoking-associated hypomethylated CpGs (P < 1.0 × 10-7), which were replicated in NTL data from The Cancer Genome Atlas. Five of these loci were previously reported as hypomethylated in smokers' blood, suggesting that blood-based biomarkers can reflect changes in the target tissue for these loci. Four CpGs border sequences carrying aryl hydrocarbon receptor binding sites and enhancer-specific histone modifications in primary alveolar epithelium and A549 lung adenocarcinoma cells. A549 cell exposure to cigarette smoke condensate increased these enhancer marks significantly and stimulated expression of predicted target xenobiotic response-related genes AHRR (P = 1.13 × 10-62) and CYP1B1 (P < 2.49 × 10-61). Expression of both genes was linked to smoking-related transversion mutations in lung tumors. Thus, smoking-associated hypomethylation may be a consequence of enhancer activation, revealing environmentally-induced regulatory elements implicated in lung carcinogenesis.
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| Overall design |
RNAseq of DMSO or cigarette smoke condensate (CSC)-treated A549 human lung adenocarcinoma cells. Cells were treated for either 48 hours or 2 weeks, as indicated.
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| Contributor(s) |
Stueve TR, Li WQ, Shi J, Marconett CN, Zhang T, Yang C, Mullen DJ, Yan C, Wheeler W, Hua X, Zhou B, Borok Z, Caporaso NE, Pesatori AC, Duan J, Laird-Offringa IA, Landi MT |
| Citation(s) |
28854564 |
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| Submission date |
Jun 11, 2015 |
| Last update date |
Jul 17, 2023 |
| Contact name |
Crystal N Marconett |
| E-mail(s) |
cmarcone@usc.edu, cmarconett@coh.org
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| Phone |
626-218-4357
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| Organization name |
City of Hope
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| Department |
Integrative Translational Sciences
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| Lab |
Crystal Marconett
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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) |
| GPL11154 |
Illumina HiSeq 2000 (Homo sapiens) |
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| Samples (11)
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| GSM1708584 |
A549 RNAseq: DMSO vehicle treated for 48 Hours Replicate 2 |
| GSM1708585 |
A549 RNAseq: DMSO vehicle treated for 48 Hours Replicate 3 |
| GSM1708586 |
A549 RNAseq: 20uM Cigarette smoke condensate (CSC) treated for 48 Hours Replicate 1 |
| GSM1708587 |
A549 RNAseq: 20uM Cigarette smoke condensate (CSC) treated for 48 Hours Replicate 2 |
| GSM1708588 |
A549 RNAseq: 20uM Cigarette smoke condensate (CSC) treated for 48 Hours Replicate 3 |
| GSM1708589 |
A549 RNAseq: DMSO vehicle treated for 2 weeks Replicate 1 |
| GSM1708590 |
A549 RNAseq: DMSO vehicle treated for 2 weeks Replicate 2 |
| GSM1708591 |
A549 RNAseq: DMSO vehicle treated for 2 weeks Replicate 3 |
| GSM1708592 |
A549 RNAseq: 20uM Cigarette smoke condensate (CSC) treated for 2 weeks Replicate 1 |
| GSM1708593 |
A549 RNAseq: 20uM Cigarette smoke condensate (CSC) treated for 2 weeks Replicate 2 |
| GSM1708594 |
A549 RNAseq: 20uM Cigarette smoke condensate (CSC) treated for 2 weeks Replicate 3 |
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| Relations |
| BioProject |
PRJNA286733 |
| SRA |
SRP059363 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE69770_RAW.tar |
8.6 Mb |
(http)(custom) |
TAR (of TXT) |
SRA Run Selector |
| Raw data are available in SRA |
| Processed data provided as supplementary file |
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