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| Status |
Public on Feb 09, 2017 |
| Title |
∆DNMT3B4-del Contributes to Aberrant DNA Methylation Patterns in Lung Tumorigenesis |
| Organism |
Mus musculus |
| Experiment type |
Methylation profiling by high throughput sequencing
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| Summary |
Aberrant DNA methylation is a hallmark of cancer but mechanisms contributing to the abnormality remain elusive. Here, we report that most of lung cancer cell lines tested expressed predominantly ∆DNMT3B-del whereas normal bronchial epithelial cells expressed equal quantities of ∆DNMT3B and ∆DNMT3B-del. We demonstrate biological impacts of ∆DNMT3B4-del, a ∆DNMT3B-del isoform, in a transgenic mouse model. Expression of ∆DNMT3B4-del in the mouse lungs resulted in an increased global DNA hypomethylation, focal DNA hypermethylation, epithelial hyperplastia and tumor formation when challenged with a tobacco carcinogen. In patients with non-small cell lung cancer, 83% of the primary tumors expressed predominantly ∆DNMT3B-del. Our results demonstrate ∆DNMT3B4-del as a critical factor in developing aberrant DNA methylation during lung tumorigenesis.
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| Overall design |
Methyl binding domain protein-enriched genome sequencing (MBD-Seq) approach was employed to analyze methylated DNA regions in the genomic DNA samples. We constructed 6 libraries of genomic DNA samples from mouse lung tissues including 3 from wild-type mice and 3 from the transgenic mice. Each group (wild type or transgenic), therefore, consisted of three biological replicates.
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| Contributor(s) |
Ma MZ, Lin L, Carrillo J, Bhutani M, Pathak A, Ren H, Song J, Mao L |
| Citation(s) |
26629529 |
| |
| Submission date |
May 15, 2015 |
| Last update date |
May 15, 2019 |
| Contact name |
Jose Adrian Carrillo |
| E-mail(s) |
carrillo@umd.edu
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| Organization name |
University of Maryland
|
| Department |
Department of Animal and Avian Sciences
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| Lab |
Song's lab
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| Street address |
1413 Animal Sciences Center
|
| City |
College Park |
| State/province |
MD |
| ZIP/Postal code |
20742-2311 |
| Country |
USA |
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| Platforms (1) |
| GPL9185 |
Illumina Genome Analyzer (Mus musculus) |
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| Samples (6)
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| Relations |
| BioProject |
PRJNA284114 |
| SRA |
SRP058379 |
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