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Learn MoreAtypical teratoid/rhabdoid tumor (AT/RT), which harbors INI1 mutation and exhibits a characteristic histology of rhabdoid cells, has a poor prognosis because of the lack of effective treatments. Here we established human INI1-deficient pluripotent stem cells (hPSCs), which developed AT/RT formation in vivo. We revealed that the activation of ESC-like signature leads to rhabdoid phenotype in tumor by OSKM or c-MYC induction. Finally, we performed CRISPR/Cas9 knockout screening to inhibit activation of ESC-like signature in AT/RT. Our effort identified candidate genes including RAD21 that encodes a key component within the cohesin complex. Notably, chemical inhibition of HDAC8 that indirectly targets the function of cohesin with simultaneous inhibition of EZH2 efficiently suppressed the activation of ESC-like signature and inhibited the growth of AT/RT cells both in vitro and in vivo. SOURCE: Yasuhiro Yamada (yasu@ims.u-tokyo.ac.jp) - Division of Stem Cell Pathology University of Tokyo
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