Titel (eng)

Decoding molecular programs in melanoma brain metastases

Autor*in

Josefine Radke   University of Veterinary Medicine, Vienna

Elisa Schumann

Julia Onken

Randi Koll

Güliz Acker

Bohdan Bodnar

Carolin Senger

Sascha Tierling

Markus Möbs

Peter Vajkoczy

Anna Vidal   University of Veterinary Medicine, Vienna

Sandra Högler   University of Veterinary Medicine, Vienna

Petra Kodajova   University of Veterinary Medicine, Vienna

Dana Westphal

Friedegund Meier

Frank Heppner

Susanne Kreuzer-Redmer   University of Veterinary Medicine, Vienna

Florian Grebien   University of Veterinary Medicine, Vienna

Karsten Jürchott

Torben Redmer   University of Veterinary Medicine, Vienna

Verlag

Springer Nature

Beschreibung (eng)

Melanoma brain metastases (MBM) variably respond to therapeutic interventions; thus determining patient's prognosis. However, the mechanisms that govern therapy response are poorly understood. Here, we use a multi-OMICS approach and targeted sequencing (TargetSeq) to unravel the programs that potentially control the development of progressive intracranial disease. Molecularly, the expression of E-cadherin (Ecad) or NGFR, the BRAF mutation state and level of immune cell infiltration subdivides tumors into proliferative/pigmented and invasive/stem-like/therapy-resistant irrespective of the intracranial location. The analysis of MAPK inhibitor-naive and refractory MBM reveals switching from Ecad-associated into NGFR-associated programs during progression. NGFR-associated programs control cell migration and proliferation via downstream transcription factors such as SOX4. Moreover, global methylome profiling uncovers 46 differentially methylated regions that discriminate BRAFmut and wildtype MBM. In summary, we propose that the expression of Ecad and NGFR sub- classifies MBM and suggest that the Ecad-to-NGFR phenotype switch is a rate-limiting process which potentially indicates drug-response and intracranial progression states in melanoma patients.

Sprache des Objekts

Englisch

Datum

2022

Rechte

Dieses Werk bzw. dieser Inhalt steht unter einer
CC BY 4.0 - Creative Commons Namensnennung 4.0 International Lizenz.

CC BY 4.0 International

http://creativecommons.org/licenses/by/4.0/

Mitglied in der/den Collection(s) (1)