|
| Status |
Public on Sep 30, 2015 |
| Title |
Dynamic Reprogramming of DNA Methylation in SETD2-Deregulated Renal Cell Carcinoma |
| Organism |
Homo sapiens |
| Experiment type |
Methylation profiling by genome tiling array
|
| Summary |
Clear cell renal cell carcinomas (ccRCCs) harbor frequent mutations in epigenetic modifiers including SETD2, the writer for H3K36me3. We profiles DNA methylation across cell line models of SETD2 inactivation and SETD2 mutated primary tumors as this epigenetic mark is linked to H3K36me3 and is a targetable mark for cancer therapy. SETD2 depleted cell line models (long-term and acute) exhibited a hypermethylation phenotype coinciding with ectopic gains in H3K36me3 centered across intergenic regions adjacent to low expression genes that became upregulated with dysregulation of the epigenome. Poised enhancers of developmental genes demonstrated enrichment for the hypermethylation phenotype. Deregulation of the epigenome observed in the cell line models was recapitulated in SETD2 mutated primary ccRCC, papillary renal cell carcinomas, and lung adenocarcinomas.
|
| |
|
| Overall design |
786-O parental ccRCC cell line was used to derive isogenic clones depleted of SETD2 through zinc-finger nuclease mediated knockout. NCCIT cells were transfected with siRNAs against SETD2. Genomic DNA was extracted and submitted for HumanMethylation 450 BeadChip Array processing.
|
| |
|
| Contributor(s) |
Tiedemann RL, Hlady RA, Hanavan PD, Lake DF, Tibes R, Lee J, Choi J, Ho TH, Robertson KD |
| Citation(s) |
26646321 |
| |
| Submission date |
Jul 08, 2015 |
| Last update date |
Mar 22, 2019 |
| Contact name |
Keith D Robertson |
| E-mail(s) |
robertson.keith@mayo.edu
|
| Phone |
507-266-4886
|
| Organization name |
Mayo Clinic
|
| Department |
Molecular Pharmacology & Experimental Therapeutics
|
| Lab |
Epigenetic Etiology of Human Disease Laboratory
|
| Street address |
200 First Street SW, Stabile 12-70
|
| City |
Rochester |
| State/province |
MN |
| ZIP/Postal code |
55905 |
| Country |
USA |
| |
|
| Platforms (1) |
| GPL13534 |
Illumina HumanMethylation450 BeadChip (HumanMethylation450_15017482) |
|
| Samples (4)
|
|
| Relations |
| BioProject |
PRJNA289252 |
Less...
More...