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Melanoma-derived iPCCs show differential tumorigenicity and therapy response

Summary. A point mutation in the BRAF gene, leading to a constitutively active form of the protein, is present in 45%-60% of patients and acts as a key driver in melanoma. Shortly after therapy induction, resistance to MAPK pathway-specific inhibitors develops, indicating that pathway inhibition is...

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Hauptverfasser: Bernhardt, Mathias (VerfasserIn) , Novak, Daniel (VerfasserIn) , Orouji, Elias (VerfasserIn) , Knappe, Nathalie (VerfasserIn) , Weina, Kasia (VerfasserIn) , Reith, Maike (VerfasserIn) , Gebhardt, Christoffer (VerfasserIn) , Umansky, Viktor (VerfasserIn) , Utikal, Jochen (VerfasserIn)
Dokumenttyp: Article (Journal)
Sprache:Englisch
Veröffentlicht: April 6, 2017
In: Stem cell reports
Year: 2017, Jahrgang: 8, Heft: 5, Pages: 1379-1391
ISSN:2213-6711
DOI:10.1016/j.stemcr.2017.03.007
Online-Zugang:Verlag, Volltext: http://dx.doi.org/10.1016/j.stemcr.2017.03.007
Verlag, Volltext: http://www.sciencedirect.com/science/article/pii/S2213671117301133
Volltext
Verfasserangaben:Mathias Bernhardt, Daniel Novak, Yassen Assenov, Elias Orouji, Nathalie Knappe, Kasia Weina, Maike Reith, Lionel Larribere, Christoffer Gebhardt, Christoph Plass, Viktor Umansky, Jochen Utikal
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Zusammenfassung:Summary. A point mutation in the BRAF gene, leading to a constitutively active form of the protein, is present in 45%-60% of patients and acts as a key driver in melanoma. Shortly after therapy induction, resistance to MAPK pathway-specific inhibitors develops, indicating that pathway inhibition is circumvented by epigenetic mechanisms. Here, we mimicked epigenetic modifications in melanoma cells by reprogramming them into metastable induced pluripotent cancer cells (iPCCs) with the ability to terminally differentiate into non-tumorigenic lineages. iPCCs and their differentiated progeny were characterized by an increased resistance against targeted therapies, although the cells harbor the same oncogenic mutations and signaling activity as the parental melanoma cells. Furthermore, induction of a pluripotent state allowed the melanoma-derived cells to acquire a non-tumorigenic cell fate, further suggesting that tumorigenicity is influenced by the cell state.
Beschreibung:Gesehen am 28.05.2018
Beschreibung:Online Resource
ISSN:2213-6711
DOI:10.1016/j.stemcr.2017.03.007

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