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| Status |
Public on Dec 18, 2019 |
| Title |
DNA methylation instability by BRAF-mediated TET silencing and lifestyle-exposure divides colon cancer pathways [tumor, paired normal] |
| Organism |
Homo sapiens |
| Experiment type |
Methylation profiling by genome tiling array
Methylation profiling by array
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| Summary |
Promoter hypermethylation divides colon cancers into subtypes with and without a CpG island methylator phenotype (CIMP). Here, we performed genome-wide DNA methylation profiling of colonic normal and tumor tissues to dissect development of CpG hypermethylation in colon carcinogenesis. This identified age-environment related versus genetically driven CpG hypermethylation, the latter being associated with CIMP cancers. We found a strong association between BRAFV600E mutation and downregulation of the DNA demethylases TET1 and TET2. Expression of BRAFV600E in CIMP cancer cells suppressed TET1 transcription, which was sufficient to establish hypermethylation at CIMP genes promoters, including that of TET2. This phenotype was reverted by the BRAFV600E inhibitor vemurafenib. Thus, BRAFV600E, via impairment of cytosine de-methylation, is a genetic driver of CIMP in colon tumorigenesis.
Genome-wide DNA methylation profiling of adjacent non-tumor colon tissue and colon adenocarcinoma samples. The Illumina Infinium 27k Human DNA methylation Beadchip v1.2 was used to obtain DNA methylation profiles across approximately 27,000 CpGs. Samples included 8 colon cancer tissues and their associated healthy mucosa (CAM).
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| Overall design |
Bisulfite-converted DNA from the 16 samples were hybridised to the Illumina Infinium 27k Human Methylation Beadchip v1.2.
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| Contributor(s) |
Noreen F, Truninger K, Schär P |
| Citation(s) |
31842975 |
| Submission date |
May 03, 2017 |
| Last update date |
Jul 25, 2021 |
| Contact name |
Faiza Noreen |
| E-mail(s) |
faiza.noreen@unibas.ch
|
| Organization name |
University of Basel
|
| Department |
Department of Biomedicine
|
| Street address |
Mattenstrasse 28
|
| City |
Basel |
| ZIP/Postal code |
4058 |
| Country |
Switzerland |
| |
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| Platforms (1) |
| GPL8490 |
Illumina HumanMethylation27 BeadChip (HumanMethylation27_270596_v.1.2) |
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| Samples (16)
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| This SubSeries is part of SuperSeries: |
| GSE98534 |
DNA methylation instability by BRAF-mediated TET silencing and lifestyle-exposure divides colon cancer pathways |
|
| Relations |
| BioProject |
PRJNA385367 |
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