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Cancer Genet. 2014 Sep;207(9):365-72. doi: 10.1016/j.cancergen.2014.04.004. Epub 2014 Apr 13.

Mechanisms by which SMARCB1 loss drives rhabdoid tumor growth.

Author information

1
Department of Pediatric Oncology, Dana-Farber Cancer Institute, Boston, MA, USA; Division of Hematology/Oncology, Children's Hospital, Boston, MA, USA; Department of Pediatrics, Harvard Medical School, Boston, MA, USA; Broad Institute of Harvard and Massachusetts Institute of Technology, Boston, MA, USA.
2
Department of Pediatric Oncology, Dana-Farber Cancer Institute, Boston, MA, USA; Division of Hematology/Oncology, Children's Hospital, Boston, MA, USA; Department of Pediatrics, Harvard Medical School, Boston, MA, USA; Broad Institute of Harvard and Massachusetts Institute of Technology, Boston, MA, USA. Electronic address: Charles_Roberts@dfci.harvard.edu.

Abstract

SMARCB1 (INI1/SNF5/BAF47), a core subunit of the SWI/SNF (BAF) chromatin-remodeling complex, is inactivated in the large majority of rhabdoid tumors, and germline heterozygous SMARCB1 mutations form the basis for rhabdoid predisposition syndrome. Mouse models validated Smarcb1 as a bona fide tumor suppressor, as Smarcb1 inactivation in mice results in 100% of the animals rapidly developing cancer. SMARCB1 was the first subunit of the SWI/SNF complex found mutated in cancer. More recently, at least seven other genes encoding SWI/SNF subunits have been identified as recurrently mutated in cancer. Collectively, 20% of all human cancers contain a SWI/SNF mutation. Consequently, investigation of the mechanisms by which SMARCB1 mutation causes cancer has relevance not only for rhabdoid tumors, but also potentially for the wide variety of SWI/SNF mutant cancers. Here we discuss normal functions of SMARCB1 and the SWI/SNF complex as well as mechanistic and potentially therapeutic insights that have emerged.

KEYWORDS:

Rhabdoid tumor; SMARCB1; SNF5; SWI/SNF; chromatin-remodeling complex

PMID:
24853101
PMCID:
PMC4195815
DOI:
10.1016/j.cancergen.2014.04.004
[Indexed for MEDLINE]
Free PMC Article

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