Mechanisms by which SMARCB1 loss drives rhabdoid tumor growth

作者：Kim Kimberly H; Roberts Charles W M^*

来源：Cancer Genetics, 2014, 207(9): 365-372.

DOI：10.1016/j.cancergen.2014.04.004

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

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 sub-units 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.

• 出版日期2014-9
• 单位MIT