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@ARTICLE{Tsai:180643,
author = {J. W. Tsai and P. Cejas and D. K. Wang and S. Patel and D.
W. Wu and P. Arounleut and X. Wei and N. Zhou and S. Syamala
and F. P. B. Dubois and A. Crane and K. Pelton and J.
Vogelzang and C. Sousa and A. Baguette and X. Chen and A. L.
Condurat and S. E. Dixon-Clarke and K. N. Zhou and S. D. Lu
and E. M. Gonzalez and M. S. Chacon and J. J. Digiacomo and
R. Kumbhani and D. Novikov and J. Hunter and M. Tsoli and D.
S. Ziegler and U. Dirksen$^*$ and N. Jäger$^*$ and G.
Balasubramanian$^*$ and C. M. Kramm and M. Nathrath and S.
Bielack and S. J. Baker and J. Zhang and J. M. McFarland and
G. Getz and F. Aguet and N. Jabado and O. Witt$^*$ and S.
Pfister$^*$ and K. L. Ligon and V. Hovestadt and C. L.
Kleinman and H. Long and D. Jones$^*$ and P. Bandopadhayay
and T. N. Phoenix},
title = {{FOXR}2 is an epigenetically regulated pan-cancer oncogene
that activates {ETS} transcriptional circuits.},
journal = {Cancer research},
volume = {82},
number = {17},
issn = {0008-5472},
address = {Philadelphia, Pa.},
publisher = {AACR},
reportid = {DKFZ-2022-01448},
pages = {2980-3001},
year = {2022},
note = {2022 Sep 2;82(17):2980-3001 / #LA:B062#},
abstract = {Forkhead Box R2 (FOXR2) is a forkhead transcription factor
located on the X chromosome whose expression is normally
restricted to the testis. In this study, we performed a
pan-cancer analysis of FOXR2 activation across more than
10,000 adult and pediatric cancer samples and found FOXR2 to
be aberrantly upregulated in $70\%$ of all cancer types and
$8\%$ of all individual tumors. The majority of tumors
$(78\%)$ aberrantly express FOXR2 through a previously
undescribed epigenetic mechanism that involves
hypomethylation of a novel promoter, which was functionally
validated as necessary for both FOXR2 expression as well as
proliferation in FOXR2-expressing cancer cells. FOXR2
expression is sufficient to enhance tumor formation, and
coopts ETS family transcriptional circuits across cancers.
Taken together, this study identifies FOXR2 as potent and
ubiquitous oncogene that is epigenetically activated across
the majority of human cancers. The identification of ETS
transcriptional circuit hijacking by FOXR2 extends the
mechanisms known to activate ETS transcription factors and
highlights a mechanism through which transcription factor
families cooperate to enhance tumorigenesis.},
cin = {ED01 / B062 / HD01 / B310 / B360},
ddc = {610},
cid = {I:(DE-He78)ED01-20160331 / I:(DE-He78)B062-20160331 /
I:(DE-He78)HD01-20160331 / I:(DE-He78)B310-20160331 /
I:(DE-He78)B360-20160331},
pnm = {312 - Funktionelle und strukturelle Genomforschung
(POF4-312)},
pid = {G:(DE-HGF)POF4-312},
typ = {PUB:(DE-HGF)16},
pubmed = {pmid:35802025},
doi = {10.1158/0008-5472.CAN-22-0671},
url = {https://inrepo02.dkfz.de/record/180643},
}