Enhancer hijacking activates oncogenic transcription factor NR4A3 in acinic cell carcinomas of the salivary glands

Journal article


Publication Details

Author(s): Haller F, Bieg M, Will R, Koerner C, Weichenhan D, Bott A, Ishaque N, Lutsik P, Moskalev E, Müller S, Baehr M, Woerner A, Kaiser B, Scherl C, Haderlein M, Kleinheinz K, Fietkau R, Iro H, Eils R, Hartmann A, Plass C, Wiemann S, Agaimy A
Journal: Nature Communications
Publication year: 2019
Volume: 10
Journal issue: 1
ISSN: 2041-1723


Abstract

The molecular pathogenesis of salivary gland acinic cell carcinoma (AciCC) is poorly understood. The secretory Ca-binding phosphoprotein (SCPP) gene cluster at 4q13 encodes structurally related phosphoproteins of which some are specifically expressed at high levels in the salivary glands and constitute major components of saliva. Here we report on recurrent rearrangements [t(4;9)(q13;q31)] in AciCC that translocate active enhancer regions from the SCPP gene cluster to the region upstream of Nuclear Receptor Subfamily 4 Group A Member 3 (NR4A3) at 9q31. We show that NR4A3 is specifically upregulated in AciCCs, and that active chromatin regions and gene expression signatures in AciCCs are highly correlated with the NR4A3 transcription factor binding motif. Overexpression of NR4A3 in mouse salivary gland cells increases expression of known NR4A3 target genes and has a stimulatory functional effect on cell proliferation. We conclude that NR4A3 is upregulated through enhancer hijacking and has important oncogenic functions in AciCC.


FAU Authors / FAU Editors

Lehrstuhl für Allgemeine Pathologie und Pathologische Anatomie
Fietkau, Rainer Prof. Dr.
Lehrstuhl für Strahlentherapie
Haderlein, Marlen Dr. med.
Strahlenklinik
Hartmann, Arndt Prof. Dr. med.
Lehrstuhl für Allgemeine Pathologie und Pathologische Anatomie
Iro, Heinrich Prof. Dr.
Lehrstuhl für Hals-, Nasen- und Ohrenheilkunde
Moskalev, Evgeny Dr.
Pathologisches Institut


External institutions with authors

Charité - Universitätsmedizin Berlin
Deutsches Krebsforschungszentrum (DKFZ)


How to cite

APA:
Haller, F., Bieg, M., Will, R., Koerner, C., Weichenhan, D., Bott, A.,... Agaimy, A. (2019). Enhancer hijacking activates oncogenic transcription factor NR4A3 in acinic cell carcinomas of the salivary glands. Nature Communications, 10(1). https://dx.doi.org/10.1038/s41467-018-08069-x

MLA:
Haller, Florian, et al. "Enhancer hijacking activates oncogenic transcription factor NR4A3 in acinic cell carcinomas of the salivary glands." Nature Communications 10.1 (2019).

BibTeX: 

Last updated on 2019-07-02 at 09:23