Rhabdoid Tumors: An Initial Clue to the Role of Chromatin Remodeling in Cancer. (25th February 2013)

• Record Type: Journal Article
• Authors: Lee, Ryan S.; Roberts, Charles W. M.
• Is Part Of: Brain pathology. Volume 23:Number 2(2013:Mar.)
• Page Start: 200
• Page End: 205
• Publication Date: 2013-02-25
• Subjects: Nervous system -- Diseases -- Periodicals; Brain -- Diseases -- Periodicals; Neurology -- Periodicals; Brain Diseases -- Periodicals; Cerveau -- Maladies -- Périodiques; Système nerveux -- Maladies -- Périodiques; Neurologie -- Périodiques; 616.805
• DOI: 10.1111/bpa.12021
• Languages: English
• ISSNs: 1015-6305

Abstract

<abstract abstract-type="main"> <title>Abstract</title> <p>The discovery of biallelic, inactivating <italic>SMARCB1</italic> mutations in rhabdoid tumors (RTs) over a decade ago represented the first recognized link between chromatin remodeling and tumor suppression. SMARCB1 is a core subunit of the SWI/SNF chromatin remodeling complex, and the recent emergence of frequent mutations in genes that encode subunits of this complex across a wide variety of cancers suggests that perturbation of this chromatin remodeling complex constitutes a key driver of cancer formation. Despite the highly aggressive nature of RTs, they are genetically simple cancers that appear to lack chromosomal instability and contain very few mutations. Indeed, the mutation rate in RTs is among the lowest of all cancers sequenced, with loss of <italic>SMARCB1</italic> as essentially the sole recurrent event. Given the genetic simplicity of this disease, understanding the chromatin dysregulation caused by <italic>SMARCB1</italic> loss may provide more general insight into how epigenetic alterations can contribute to oncogenic transformation and may reveal opportunities for targeted therapy not only of RT but also the variety of other SWI/SNF mutant cancers.</p> </abstract>