SMARCB1-deficient cancers result from the mutation of one single gene, SMARCB1, whereas most cancers are the result of the combined effects of multiple gene mutations.
SMARCB1 is a known tumor suppressor and, as a core subunit of the SWI/SNF chromatin remodeling complex, is involved in the epigenetic regulation of gene transcription. Exactly how SMARCB1 mutation leads to tumors and deregulates the SWI/SNF complex is not yet fully understood, but it is the initiating event in a number of cancers and the sole driver in certain pediatric and young adult ones. Tumors initiated and driven solely by SMARCB1-deficiency (the biallelic loss of function in both SMARCB1 alleles) are relatively rare, but up to 25% of all cancers exhibit mutations of the SWI/SNF complex — including SMARCB1 — at some point in their evolution.
Single mutation SMARCB1-deficient cancers provide a kind of “pure” paradigm for cancer research. Understanding their mechanisms and finding effective treatments can pave the way for next generation targeted- and immuno-therapies relevant to the wider cancer world.
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KNOWN SMARCB1-DEFICIENT CANCERS
SMARCB1-deficiency as the sole initiator and driver of certain cancers was first discovered 25 years ago in pediatric malignant rhabdoid tumors (MRT). This in turn led to its discovery in numerous other cancers, including atypical teratoid rhabdoid tumor (ATRT, the brain countepart of MRT), epithelioid sarcoma, SMARCB1-deficient sinonasal carcinoma, renal medullary carcinoma (RMC), and pediatric chordoma.