About Smarcb1

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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Olivier Delattre & Franck Bourdeaut, Curie Institute – Paris, France

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.

MORE INFORMATION

Les cancers de l’enfant sous la loupe des chercheurs, à l’Institut Curie

Florence Rosier
L’unité de soins en oncopédiatrie et le laboratoire d’Olivier Delattre, lauréat du Grand Prix de l’Inserm 2022, travaillent en étroite synergie pour améliorer la prise en charge des jeunes patients….…

SMARCB1: GENETIC ‘CANARY IN A COAL MINE’ SPARKS RESEARCH

Erin Podolak
Pediatric cancers tend to have quiet genomes, with few genetic culprits underlying processes that go wrong in cancer. When starting his research career, Charles W.M. Roberts, MD, PhD, St. Jude Comprehensive Cancer Center director, focused on understanding the mechanisms behind the biology of cancer cells.…

SMARCB1-Deficient Cancers: Novel Molecular Insights and Therapeutic Vulnerabilities

Garret W. Cooper, Andrew L. Hong
Loss of SMARCB1 has been identified as the sole mutation in a number of rare pediatric and adult cancers, most of which have a poor prognosis despite intensive therapies including surgery, radiation, and chemotherapy……

The SWI/SNF complex in cancer – biology, biomarkers and therapy

Priya Mittal, Charles Roberts
Cancer genome-sequencing studies have revealed a remarkably high prevalence of mutations in genes encoding subunits of the SWI/SNF chromatin-remodelling complexes, with nearly 25% of all cancers harbouring aberrations in one or more of these genes……

Immunotherapy for SMARCB1-Deficient Sarcomas: Current Evidence and Future Developments

Carine Ngo, Sophie Postel-Vinay
Mutations in subunits of the SWItch Sucrose Non-Fermentable (SWI/SNF) complex occur in 20% of all human tumors. Among these, the core subunit SMARCB1 is the most frequently mutated, and SMARCB1 loss represents a founder driver event in several malignancies……