Peter Ruzanov, Valentina Evdokimova, Manideep C Pachva, Alon Minkovich, Zhenbo Zhang, Sofya Langman, Hendrik Gassmann, Uwe Thiel, Marija Orlic-Milacic, Syed H Zaidi, Vanya Peltekova, Lawrence E Heisler, Manju Sharma, Michael E Cox, Trevor D McKee, Mark Zaidi, Eve Lapouble, John D McPherson, Olivier Delattre, Laszlo Radvanyi, Stefan Eg Burdach, Lincoln D Stein, Poul H Sorensen
Aberrant expression of ETS transcription factors characterizes numerous human malignancies. Many of these proteins, including EWS::FLI1 and EWS::ERG fusions in Ewing sarcoma (EwS) and TMPRSS2::ERG in prostate cancer (PCa), drive oncogenic programs via binding to GGAA repeats. We report here that both EWS::FLI1 and ERG bind and transcriptionally activate GGAA-rich pericentromeric heterochromatin. The respective pathogen-like HSAT2 and HSAT3 RNAs, together with LINE, SINE, ERV and other repeat transcripts, are expressed in EwS and PCa tumors, secreted in extracellular vesicles (EVs) and are highly elevated in plasma of EwS patients with metastatic disease...
March 26, 2024: Journal of Clinical Investigation