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| Status |
Public on Nov 27, 2015 |
| Title |
Genome-wide DNA methylation signature in lung adenocarcinomas has prognostic impact |
| Organism |
Homo sapiens |
| Experiment type |
Methylation profiling by genome tiling array
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| Summary |
Purpose: DNA methylation alterations are early events in tumorigenesis and important in the regulation of gene expression in cancer cells. Lung cancer has in general a poor prognosis, and a deeper insight into the epigenetic landscape in lung adenocarcinoma tumors and its prognostic implications is needed.
Experimental Design: We determined whole-genome DNA methylation profiles of 164 lung adenocarcinoma samples and 19 samples of matched normal lung tissue samples using the Illumina Infinium 450K array. The methylation levels were correlated with gene expression levels analyzed by the Agilent 60K mRNA expression array. Methylation changes were studied specifically in tumors from never-smoking patients, and in tumors with mutations in the EGFR-, KRAS- or TP53 genes, and survival analyses were performed.
Results: We identified a large number of differentially methylated CpGs in lung adenocarcinoma tissue, and different methylation profiles in tumors from smokers and never-smokers. Specific methylation profiles were observed in tumors with mutations in the EGFR-, KRAS- or TP53 gene. Both positive and negeative correlations between DNA methylation levels and mRNA expression levels were seen. Methylation profiles of the tumor samples identified clusters of patients with distinct prognosis. A prognostic index based on the methylation levels of 33 CpGs was established, and validated in an independent cohort of lung adenocarcinoma patients from the TCGA project. Among the CpGs in the prognostic signature, some were localized in the HOX B and HOX C gene clusters.
Conclusions: Methylation differences mirror biological important features the etiology of lung adenocarcinomas and influence prognosis.
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| Overall design |
Bisulphite converted DNA from the 183 samples were hybridized to the Illumina Infinium 450k Human Methylation Beadchip
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| Contributor(s) |
Bjaanæs MM, Fleischer T, Halvorsen AR, Daunay A, Busato F, Solberg S, Jørgensen L, Kure E, Edvardsen H, Børresen-Dale A, Brustugun OT, Tost J, Kristensen V, Helland Å |
| Citation(s) |
26601720 |
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| Submission date |
Mar 12, 2015 |
| Last update date |
Mar 22, 2019 |
| Contact name |
Thomas Fleischer |
| E-mail(s) |
[email protected]
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| Organization name |
Oslo University Hospital
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| Department |
Department of Cancer Genetics, Institute for Cancer Research
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| Street address |
Ullernchausséen 70
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| City |
Oslo |
| ZIP/Postal code |
0310 |
| Country |
Norway |
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| Platforms (1) |
| GPL13534 |
Illumina HumanMethylation450 BeadChip (HumanMethylation450_15017482) |
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| Samples (183)
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| Relations |
| BioProject |
PRJNA278141 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE66836_RAW.tar |
1.6 Gb |
(http)(custom) |
TAR (of IDAT) |
| Processed data included within Sample table |
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