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SMARCB1-Deficient Cancers: Novel Molecular Insights and Therapeutic Vulnerabilities

Overview
Journal Cancers (Basel)
Publisher MDPI
Specialty Oncology
Date 2022 Jul 27
PMID 35892904
Authors
Garrett W Cooper
Andrew L Hong
Affiliations
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Abstract

SMARCB1 is a critical component of the BAF complex that is responsible for global chromatin remodeling. Loss of SMARCB1 has been implicated in the initiation of cancers such as malignant rhabdoid tumor (MRT), atypical teratoid rhabdoid tumor (ATRT), and, more recently, renal medullary carcinoma (RMC). These SMARCB1-deficient tumors have remarkably stable genomes, offering unique insights into the epigenetic mechanisms in cancer biology. Given the lack of druggable targets and the high mortality associated with SMARCB1-deficient tumors, a significant research effort has been directed toward understanding the mechanisms of tumor transformation and proliferation. Accumulating evidence suggests that tumorigenicity arises from aberrant enhancer and promoter regulation followed by dysfunctional transcriptional control. In this review, we outline key mechanisms by which loss of SMARCB1 may lead to tumor formation and cover how these mechanisms have been used for the design of targeted therapy.

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References
1.
Merker V, Esparza S, Smith M, Stemmer-Rachamimov A, Plotkin S . Clinical features of schwannomatosis: a retrospective analysis of 87 patients. Oncologist. 2012; 17(10):1317-22. PMC: 3481897. DOI: 10.1634/theoncologist.2012-0162. View
2.
Biegel J, Zhou J, RORKE L, Stenstrom C, Wainwright L, Fogelgren B . Germ-line and acquired mutations of INI1 in atypical teratoid and rhabdoid tumors. Cancer Res. 1999; 59(1):74-9. View
3.
Tsurusaki Y, Okamoto N, Ohashi H, Mizuno S, Makita Y, Fukuda M . Coffin-Siris syndrome is a SWI/SNF complex disorder. Clin Genet. 2013; 85(6):548-54. DOI: 10.1111/cge.12225. View
4.
Chasse M, Johnson B, Boguslawski E, Sorensen K, Rosien J, Kang M . Mithramycin induces promoter reprogramming and differentiation of rhabdoid tumor. EMBO Mol Med. 2020; 13(2):e12640. PMC: 7863405. DOI: 10.15252/emmm.202012640. View
5.
Carugo A, Minelli R, Sapio L, Soeung M, Carbone F, Robinson F . p53 Is a Master Regulator of Proteostasis in SMARCB1-Deficient Malignant Rhabdoid Tumors. Cancer Cell. 2019; 35(2):204-220.e9. PMC: 7876656. DOI: 10.1016/j.ccell.2019.01.006. View