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| Status |
Public on Jan 26, 2012 |
| Title |
The DNA methylation landscape of small cell lung cancer |
| Organism |
Homo sapiens |
| Experiment type |
Methylation profiling by genome tiling array
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| Summary |
Small cell lung cancer (SCLC) is a disease characterized by aggressive clinical behavior and lack of effective therapy. Due to its high tendency of early dissemination, only a third of patients have limited-stage disease at the time of diagnosis. SCLC is thought to derive from neuroendocrine cells of the lung. Although several molecular abnormalities in SCLC have been described, there are relatively few studies on epigenetic alterations in this type of tumor. Here, we have used methylation profiling with the methylated CpG island recovery assay (MIRA) in combination with microarrays and conducted the first genome-scale analysis of methylation changes that occur in primary SCLC and SCLC cell lines. Among hundreds of tumor-specifically methylated genes, we identified 73 gene targets that are methylated in more than 77% of primary SCLC tumors, most of which have never been linked to aberrant methylation in tumors. These targets have excellent potential for development of biomarkers for early detection of SCLC. SCLC cell lines had an ~3-fold greater number of hypermethylated genes than primary tumors. Gene ontology analysis indicated a significant enrichment of methylated genes functioning as transcription factors and in processes of neuronal differentiation. Motif analysis of tumor-specific methylated regions identified enrichment of binding sites for several neural cell fate-specifying transcription factors including NEUROD1, HAND1, ZNF423 and REST. We hypothesize that functional inactivation of their corresponding binding sites by DNA methylation can lead to an escape route for early progenitor cells towards the malignant state and may contribute to the origin of SCLC.
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| Overall design |
Comparison between healthy and SCLC tumor DNA methylation profiles
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| Contributor(s) |
Kalari S, Jung M, Kernstine KH, Takahashi T, Pfeifer G |
| Citation(s) |
22907430 |
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| Submission date |
Jan 25, 2012 |
| Last update date |
May 10, 2013 |
| Contact name |
Marc Jung |
| E-mail(s) |
[email protected]
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| Organization name |
City Of Hope
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| Department |
Biology
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| Lab |
Gerd Pfeifer
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| Street address |
1500 East Duarte Street
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| City |
Duarte |
| State/province |
CA |
| ZIP/Postal code |
91010 |
| Country |
USA |
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| Platforms (1) |
| GPL15160 |
NimbleGen Human DNA Methylation 3x720K CpG Island Plus RefSeq Promoter Arrays (090618_HG18_CpG_Refseq_Prom_MeDIP) |
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| Samples (29)
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| Relations |
| BioProject |
PRJNA152713 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE35341_RAW.tar |
786.8 Mb |
(http)(custom) |
TAR (of GFF, PAIR) |
| Processed data included within Sample table |
| Processed data provided as supplementary file |
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