Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

DNA methylation instability by BRAF-mediated TET silencing and lifestyle-exposure divides colon cancer pathways

ABSTRACT: DNA methylation instability by BRAF-mediated TET silencing and lifestyle-exposure divides colon cancer pathways

PROVIDER: PRJNA385362 | ENA |

REPOSITORIES: ENA

ACCESS DATA

Json Xml

Similar Datasets

DNA methylation instability by BRAF-mediated TET silencing and lifestyle-exposure divides colon cancer pathways [Colo320 cell line]

Project description:DNA methylation instability by BRAF-mediated TET silencing and lifestyle-exposure divides colon cancer pathways [Colo320 cell line]

| PRJNA514303 | ENA

DNA methylation instability by BRAF-mediated TET silencing and lifestyle-exposure divides colon cancer pathways [BrafV637E knock-in ]

Project description:DNA methylation instability by BRAF-mediated TET silencing and lifestyle-exposure divides colon cancer pathways [BrafV637E knock-in ]

| PRJNA427811 | ENA

DNA methylation instability by BRAF-mediated TET silencing and lifestyle-exposure divides colon cancer pathways [BrafV637E knock-in ]

Project description: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.

2019-12-18 | GSE108606 | GEO

DNA methylation instability by BRAF-mediated TET silencing and lifestyle-exposure divides colon cancer pathways [Colo320 cell line]

2019-12-18 | GSE124915 | GEO

DNA methylation instability by BRAF-mediated TET silencing and lifestyle-exposure divides colon cancer pathways [Caco2 cell line]

2019-12-18 | GSE98533 | GEO

DNA methylation instability by BRAF-mediated TET silencing and lifestyle-exposure divides colon cancer pathways [3 cell lines]

2019-12-18 | GSE98532 | GEO

DNA methylation instability by BRAF-mediated TET silencing and lifestyle-exposure divides colon cancer pathways [tumor, paired normal]

2019-12-18 | GSE98531 | GEO

DNA methylation instability by BRAF-mediated TET silencing and lifestyle-exposure divides colon cancer pathways.

Project description:BackgroundAberrations in DNA methylation are widespread in colon cancer (CC). Understanding origin and progression of DNA methylation aberrations is essential to develop effective preventive and therapeutic strategies. Here, we aimed to dissect CC subtype-specific methylation instability to understand underlying mechanisms and functions.MethodsWe have assessed genome-wide DNA methylation in the healthy normal colon mucosa (HNM), precursor lesions and CCs in a first comprehensive study to delineate epigenetic change along the process of colon carcinogenesis. Mechanistically, we used stable cell lines, genetically engineered mouse model of mutant BRAFV600E and molecular biology analysis to establish the role of BRAFV600E-mediated-TET inhibition in CpG-island methylator phenotype (CIMP) inititation.ResultsWe identified two distinct patterns of CpG methylation instability, determined either by age-lifestyle (CC-neutral CpGs) or genetically (CIMP-CpGs). CC-neutral-CpGs showed age-dependent hypermethylation in HNM, all precursors, and CCs, while CIMP-CpGs showed hypermethylation specifically in sessile serrated adenomas/polyps (SSA/Ps) and CIMP-CCs. BRAFV600E-mutated CCs and precursors showed a significant downregulation of TET1 and TET2 DNA demethylases. Stable expression of BRAFV600E in nonCIMP CC cells and in a genetic mouse model was sufficient to repress TET1/TET2 and initiate hypermethylation at CIMP-CpGs, reversible by BRAFV600E inhibition. BRAFV600E-driven CIMP-CpG hypermethylation occurred at genes associated with established CC pathways, effecting functional changes otherwise achieved by genetic mutation in carcinogenesis.ConclusionsHence, while age-lifestyle-driven hypermethylation occurs generally in colon carcinogenesis, BRAFV600E-driven hypermethylation is specific for the "serrated" pathway. This knowledge will advance the use of epigenetic biomarkers to assess subgroup-specific CC risk and disease progression.

| S-EPMC6916434 | biostudies-literature

DNA methylation instability by BRAF-mediated TET silencing and lifestyle-exposure divides colon cancer pathways

Project description:This SuperSeries is composed of the SubSeries listed below.

2019-12-18 | GSE98534 | GEO

Homo sapiens

Project description:DNA methylation instability by BRAF-mediated TET silencing and lifestyle-exposure divides colon cancer pathways [3 cell lines]

| PRJNA385365 | ENA

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

Tweets

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data