KIT Is a Frequent Target for Epigenetic Silencing in Cutaneous Melanoma View Full Text


Ontology type: schema:ScholarlyArticle      Open Access: True


Article Info

DATE

2015-02

AUTHORS

Christina Dahl, Cecilie Abildgaard, Rikke Riber-Hansen, Torben Steiniche, Johanne Lade-Keller, Per Guldberg

ABSTRACT

The receptor tyrosine kinase KIT and its ligand, stem cell factor (SCF), are essential for the proliferation and survival of normal melanocytes. In melanomas arising on mucosal, acral, and chronically sun-damaged skin, activating KIT mutations have been identified as oncogenic drivers and potent therapeutic targets. Through an initial whole-genome screen for aberrant promoter methylation in melanoma, we identified the KIT promoter as a target for hypermethylation in 43/110 melanoma cell lines, and in 3/12 primary and 11/29 metastatic cutaneous melanomas. Methylation density at the KIT promoter correlated inversely with promoter activity in vitro and in vivo, and the expression of KIT was restored after treatment with the demethylating agent 5-aza-2'-deoxycytidine. Hypermethylation of KIT showed no direct or inverse correlations with well-documented melanoma drivers. Growth of melanoma cells in the presence of SCF led to reduced KIT expression and increased methylation density at the KIT promoter, suggesting that SCF may exert a selection pressure for the loss of KIT. The frequent loss of KIT in cutaneous melanoma by promoter hypermethylation suggests that distinct KIT signaling pathways have opposing roles in the pathogenesis of melanoma subtypes. More... »

PAGES

516-524

Identifiers

URI

http://scigraph.springernature.com/pub.10.1038/jid.2014.372

DOI

http://dx.doi.org/10.1038/jid.2014.372

DIMENSIONS

https://app.dimensions.ai/details/publication/pub.1039579995

PUBMED

https://www.ncbi.nlm.nih.gov/pubmed/25178104


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HOW TO GET THIS DATA PROGRAMMATICALLY:

JSON-LD is a popular format for linked data which is fully compatible with JSON.

curl -H 'Accept: application/ld+json' 'https://scigraph.springernature.com/pub.10.1038/jid.2014.372'

N-Triples is a line-based linked data format ideal for batch operations.

curl -H 'Accept: application/n-triples' 'https://scigraph.springernature.com/pub.10.1038/jid.2014.372'

Turtle is a human-readable linked data format.

curl -H 'Accept: text/turtle' 'https://scigraph.springernature.com/pub.10.1038/jid.2014.372'

RDF/XML is a standard XML format for linked data.

curl -H 'Accept: application/rdf+xml' 'https://scigraph.springernature.com/pub.10.1038/jid.2014.372'


 

This table displays all metadata directly associated to this object as RDF triples.

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