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  • EPAS1/HIF2α correlates with features of low-risk neuroblastoma and with adrenal chromaffin cell differentiation during sympathoadrenal development.

EPAS1/HIF2α correlates with features of low-risk neuroblastoma and with adrenal chromaffin cell differentiation during sympathoadrenal development.

Biochemical and biophysical research communications (2018-12-20)
Isabelle Westerlund, Yao Shi, Johan Holmberg
RESUMEN

The hypoxia inducible transcription factor EPAS1/HIF2α has been described as an oncogene and a potential therapeutic target in neuroblastoma. Our analysis of several neuroblastoma tumour expression datasets does not support an oncogenic role, instead EPAS1 expression is associated with better patient outcome and characteristics of low-risk tumours. Treatment with HIF2α inhibitors did not block in vitro neuroblastoma cell proliferation nor xenograft growth. In addition, we analysed single cell sequencing data sets from the developing mouse sympathoadrenal lineage, wherein expression of Epas1 was a strong predictor of differentiated adrenal chromaffin cells and negatively correlated with progenitor characteristics. This was reflected in neuroblastoma tumours wherein genes co-expressed with Epas1 during sympathoadrenal development strongly predicts favourable patient outcome and features of low-risk tumours. Thus, our analysis suggest that with the current available data EPAS1/HIF2α should not be classified as a neuroblastoma oncogene and is less likely to represent a suitable drug target in this disease.

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HIF-2 Antagonist 2, ≥98% (HPLC)

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