ARID1A Loss in Neuroblastoma Promotes the Adrenergic-to-mesenchymal Transition by Regulating Enhancer-mediated Gene Expression

Overview

Journal Sci Adv

Specialties Biology
Science

Date 2020 Aug 25

PMID 32832616

Citations 39

Authors

Hui Shi

Ting Tao

Brian J Abraham

Adam D Durbin

Mark W Zimmerman

Cigall Kadoch

A Thomas Look

Affiliations

Soon will be listed here.

Abstract

Mutations in genes encoding SWI/SNF chromatin remodeling complexes are found in approximately 20% of all human cancers, with being the most frequently mutated subunit. Here, we show that disruption of ARID1A homologs in a zebrafish model accelerates the onset and increases the penetrance of MYCN-driven neuroblastoma by increasing cell proliferation in the sympathoadrenal lineage. Depletion of ARID1A in human NGP neuroblastoma cells promoted the adrenergic-to-mesenchymal transition with changes in enhancer-mediated gene expression due to alterations in the genomic occupancies of distinct SWI/SNF assemblies, BAF and PBAF. Our findings indicate that is a haploinsufficient tumor suppressor in MYCN-driven neuroblastoma, whose depletion enhances tumor development and promotes the emergence of the more drug-resistant mesenchymal cell state.

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