About SMARCB1 Cancers

Many Different Cancers
One Single Faulty Gene: SMARCB1

SMARCB1-deficient tumors are rare and aggressive and strike mostly children and young adults. They can appear at different ages and in different parts of the body, bear different names and have different pathologies and symptoms, but they all share the same single genetic mutation: SMARCB1. Most of these tumors have no other recurrent mutations, unlike most other cancers which exhibit multiple gene mutations.

The SMARCB1 gene plays an essential role in healthy cell division and in suppressing tumors. SMARCB1 is ubiquitous and present in all cells of our body. As part of a broader set of genes called the “SWI/SNF” chromatin remodeling complex, SMARCB1 is involved “epigenetically” in the regulation of gene transcription and gene expression. In simpler terms, SMARCB1 is fundamental to determining our cells’ different structures and functions by helping regulate which genes are expressed and which genes are silenced (turned “on” or “off”) in each cell. When a cell’s SMARCB1 gene mutates or disappears altogether, malignant cells with the same defect can proliferate and become tumors.

We do not yet fully understand how loss of the SMARCB1 gene leads to tumors and deregulates the SWI/SNF complex, but we do know that it is the initiating event in a number of different cancers and the sole driver in certain pediatric and young adult ones (Malignant Rhabdoid Tumor which affects infants and young children being the prototypical one).

What’s more, 20% of all cancers, both pediatric and adult, exhibit mutations in the SWI/SNF complex later on as they grow.

SMARCB1 cancers have no effective treatments. Intense surgery, chemotherapy and radiotherapy are helpful for only a minority of patients and are associated with severe sequelae.

Listen to the Experts

Olivier Delattre & Franck BourdeautInstitut Curie (France)
Charles Roberts St. Jude Children's Research Hospital (United States)

Various SMARCB1 Cancers

25 years ago, the importance of SMARCB1 mutation in cancer was first discovered in the context of Malignant Rhabdoid Tumors (MRT). Since then, it has been found to be the initiator and driver of a number of other rare cancers, and the spectrum is expanding every year:

  • Malignant Rhabdoid Tumors (MRT) of the kidney and soft tissue

  • AT/RT of the central nervous system (the brain counterpart of MRT)

  • Desmoplastic myxoid tumor of the central nervous system

  • Cribriform neuro-epithelial tumors of the central nervous system

  • SMARCB1-deficient sinonasal carcinoma (SDSC)

  • Epithelioid sarcoma

  • Renal medullary carcinoma (RMC)

  • Undifferentiated chordoma

  • Myoepithelial carcinoma of soft tissue

  • Epithelioid malignant peripheral nerve sheath tumor

  • Schwannomatosis

  • Meningiomas

  • Extraskeletal myxoid chondrosarcoma

  • SMARCB1-deficient thyroid carcinoma

The Broader Cancer World

Over the last decade or so, cancer research has moved from an anatomic (organ based) perspective and understanding to a more transversal molecular understanding. It has also brought to the forefront the importance of epigenetic mechanisms in the formation of tumors. Epigenetic mechanisms are responsible for the normal development and maintenance of gene expression in cells (turning genes “on” or “off”) without altering the DNA sequence. When they do not function properly, tumors can form.

SMARCB1 cancers offer unique insights into these epigenetic mechanisms and serve as a kind of “pure paradigm” for cutting edge research in cancer. Unlike most cancers which have multiple mutations, both genetic and epigenetic, SMARCB1 cancers have only one single epigenetic mutation: SMARCB1. They also come in many different forms, in different parts of the body and at different ages.

Understanding how SMARCB1 mutation alone can initiate and drive cancer will teach us a lot about plasticity in cancer cells (how they change from one cell type to another and back again, pushing tumors to evolve and resist drugs) and potentially open a door to next generation targeted- and immuno-therapies relevant to the wider cancer world. Most of all, we can bring new hope to millions of cancer patients.

Listen to More Experts

Michael FrühwaldUniversity Children's Hospital Augsburg (Germany)
Mrinal GounderMemorial Sloan Kettering Cancer Center (United States)
William Foulkes McGill University (Canada)
Susan ChiDana-Farber Cancer Institute, Harvard Medical School (United States)
Joshua WaterfallInstitut Curie (France)
Nada JabadoMcGill University (Canada)
Sam BehjatiWellcome Sanger Institute (United Kingdom)
Sophie Postel-VinayGustave Roussy (France)