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000180643 1001_ $$00000-0003-0540-4330$$aTsai, Jessica W$$b0
000180643 245__ $$aFOXR2 is an epigenetically regulated pan-cancer oncogene that activates ETS transcriptional circuits.
000180643 260__ $$aPhiladelphia, Pa.$$bAACR$$c2022
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000180643 520__ $$aForkhead 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.
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000180643 7001_ $$aCejas, Paloma$$b1
000180643 7001_ $$00000-0002-2185-1782$$aWang, Dayle K$$b2
000180643 7001_ $$00000-0002-9026-0660$$aPatel, Smruti$$b3
000180643 7001_ $$00000-0001-6197-7091$$aWu, David W$$b4
000180643 7001_ $$aArounleut, Phonepasong$$b5
000180643 7001_ $$aWei, Xin$$b6
000180643 7001_ $$aZhou, Ningxuan$$b7
000180643 7001_ $$00000-0003-0476-3083$$aSyamala, Sudeepa$$b8
000180643 7001_ $$00000-0002-7654-6208$$aDubois, Frank P B$$b9
000180643 7001_ $$00000-0003-1930-279X$$aCrane, Alexander$$b10
000180643 7001_ $$aPelton, Kristine$$b11
000180643 7001_ $$aVogelzang, Jayne$$b12
000180643 7001_ $$aSousa, Cecilia$$b13
000180643 7001_ $$00000-0001-8011-2341$$aBaguette, Audrey$$b14
000180643 7001_ $$00000-0001-8283-0582$$aChen, Xiaolong$$b15
000180643 7001_ $$00000-0002-7297-3982$$aCondurat, Alexandra L$$b16
000180643 7001_ $$aDixon-Clarke, Sarah E$$b17
000180643 7001_ $$00000-0003-1567-3606$$aZhou, Kevin N$$b18
000180643 7001_ $$aLu, Sophie D$$b19
000180643 7001_ $$aGonzalez, Elizabeth M$$b20
000180643 7001_ $$aChacon, Madison S$$b21
000180643 7001_ $$aDigiacomo, Jeromy J$$b22
000180643 7001_ $$aKumbhani, Rushil$$b23
000180643 7001_ $$00000-0002-1388-9270$$aNovikov, Dana$$b24
000180643 7001_ $$aHunter, J'Ya$$b25
000180643 7001_ $$00000-0003-1155-0510$$aTsoli, Maria$$b26
000180643 7001_ $$aZiegler, David S$$b27
000180643 7001_ $$00000-0002-5435-7860$$aDirksen, Uta$$b28
000180643 7001_ $$0P:(DE-He78)bff9e3e3d86865d2b0836bb8f3ce98f3$$aJäger, Natalie$$b29
000180643 7001_ $$0P:(DE-He78)e5bb26ffbde307745ae396c2e829dac5$$aBalasubramanian, Gnanaprakash$$b30
000180643 7001_ $$00000-0002-5017-926X$$aKramm, Christof M$$b31
000180643 7001_ $$aNathrath, Michaela$$b32
000180643 7001_ $$00000-0003-2144-3153$$aBielack, Stefan$$b33
000180643 7001_ $$aBaker, Suzanne J$$b34
000180643 7001_ $$00000-0003-3350-9682$$aZhang, Jinghui$$b35
000180643 7001_ $$00000-0001-9978-480X$$aMcFarland, James M$$b36
000180643 7001_ $$00000-0002-0936-0753$$aGetz, Gad$$b37
000180643 7001_ $$00000-0001-9414-300X$$aAguet, François$$b38
000180643 7001_ $$aJabado, Nada$$b39
000180643 7001_ $$0P:(DE-He78)143af26de9d57bf624771616318aaf7c$$aWitt, Olaf$$b40
000180643 7001_ $$0P:(DE-He78)f746aa965c4e1af518b016de3aaff5d9$$aPfister, Stefan$$b41
000180643 7001_ $$00000-0002-7733-600X$$aLigon, Keith L$$b42
000180643 7001_ $$aHovestadt, Volker$$b43
000180643 7001_ $$00000-0002-5158-7126$$aKleinman, Claudia L$$b44
000180643 7001_ $$00000-0001-6849-6629$$aLong, Henry$$b45
000180643 7001_ $$0P:(DE-He78)551bb92841f634070997aa168d818492$$aJones, David$$b46$$eLast author
000180643 7001_ $$aBandopadhayay, Pratiti$$b47
000180643 7001_ $$00000-0003-4771-4003$$aPhoenix, Timothy N$$b48
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