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SMARCB1 loss induces druggable cyclin D1 deficiency via upregulation of MIR17HG in atypical teratoid rhabdoid tumors
dc.contributor.authorXue, Yibo
dc.contributor.authorZhu, Xianbing
dc.contributor.authorMeehan, Brian
dc.contributor.authorVenneti, Sriram
dc.contributor.authorMartinez, Daniel
dc.contributor.authorMorin, Geneviève
dc.contributor.authorMaïga, Rayelle I
dc.contributor.authorChen, Hongbo
dc.contributor.authorPapadakis, Andreas I
dc.contributor.authorJohnson, Radia M
dc.contributor.authorO’Sullivan, Maureen J
dc.contributor.authorErdreich‐epstein, Anat
dc.contributor.authorGotlieb, Walter H
dc.contributor.authorPark, Morag
dc.contributor.authorJudkins, Alexander R
dc.contributor.authorPelletier, Jerry
dc.contributor.authorFoulkes, William D
dc.contributor.authorRak, Janusz
dc.contributor.authorHuang, Sidong
dc.date.accessioned2020-09-02T14:57:37Z
dc.date.availableWITHHELD_13_MONTHS
dc.date.available2020-09-02T14:57:37Z
dc.date.issued2020-09
dc.identifier.citationXue, Yibo; Zhu, Xianbing; Meehan, Brian; Venneti, Sriram; Martinez, Daniel; Morin, Geneviève ; Maïga, Rayelle I ; Chen, Hongbo; Papadakis, Andreas I; Johnson, Radia M; O’Sullivan, Maureen J; Erdreich‐epstein, Anat ; Gotlieb, Walter H; Park, Morag; Judkins, Alexander R; Pelletier, Jerry; Foulkes, William D; Rak, Janusz; Huang, Sidong (2020). "SMARCB1 loss induces druggable cyclin D1 deficiency via upregulation of MIR17HG in atypical teratoid rhabdoid tumors." The Journal of Pathology 252(1): 77-87.
dc.identifier.issn0022-3417
dc.identifier.issn1096-9896
dc.identifier.urihttps://hdl.handle.net/2027.42/156416
dc.description.abstractAtypical teratoid rhabdoid tumor (ATRT) is a fatal pediatric malignancy of the central neural system lacking effective treatment options. It belongs to the rhabdoid tumor family and is usually caused by biallelic inactivation of SMARCB1, encoding a key subunit of SWI/SNF chromatin remodeling complexes. Previous studies proposed that SMARCB1 loss drives rhabdoid tumor by promoting cell cycle through activating transcription of cyclin D1 while suppressing p16. However, low cyclin D1 protein expression is observed in most ATRT patient tumors. The underlying mechanism and therapeutic implication of this molecular trait remain unknown. Here, we show that SMARCB1 loss in ATRT leads to the reduction of cyclin D1 expression by upregulating MIR17HG, a microRNA (miRNA) cluster known to generate multiple miRNAs targeting CCND1. Furthermore, we find that this cyclin D1 deficiency in ATRT results in marked in vitro and in vivo sensitivity to the CDK4/6 inhibitor palbociclib as a single agent. Our study identifies a novel genetic interaction between SMARCB1 and MIR17HG in regulating cyclin D1 in ATRT and suggests a rationale to treat ATRT patients with FDA- approved CDK4/6 inhibitors. © 2020 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.
dc.publisherJohn Wiley & Sons, Ltd
dc.subject.otherATRT
dc.subject.othercyclin D1
dc.subject.otherMIR17HG
dc.subject.otherpalbociclib
dc.subject.otherSMARCB1
dc.titleSMARCB1 loss induces druggable cyclin D1 deficiency via upregulation of MIR17HG in atypical teratoid rhabdoid tumors
dc.typeArticle
dc.rights.robotsIndexNoFollow
dc.subject.hlbsecondlevelPathology
dc.subject.hlbtoplevelHealth Sciences
dc.description.peerreviewedPeer Reviewed
dc.description.bitstreamurlhttp://deepblue.lib.umich.edu/bitstream/2027.42/156416/2/path5493.pdfen_US
dc.description.bitstreamurlhttp://deepblue.lib.umich.edu/bitstream/2027.42/156416/1/path5493_am.pdfen_US
dc.identifier.doi10.1002/path.5493
dc.identifier.sourceThe Journal of Pathology
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dc.owningcollnameInterdisciplinary and Peer-Reviewed


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