title: Vulnerabilities of mutant SWI/SNF complexes in cancer.
abstract: Cancer genome sequencing efforts have revealed the novel theme that chromatin modifiers are frequently mutated across a wide spectrum of cancers. Mutations in genes encoding subunits of SWI/SNF (BAF) chromatin remodeling complexes are particularly prevalent, occurring in 20% of all human cancers. As these are typically loss-of-function mutations and not directly therapeutically targetable, central goals have been to elucidate mechanism and identify vulnerabilities created by these mutations. Here, we discuss emerging data that these mutations lead to the formation of aberrant residual SWI/SNF complexes that constitute a specific vulnerability and discuss the potential for exploiting these dependencies in SWI/SNF mutant cancers.
authors.affiliation: Department of Pediatric Oncology, Dana-Farber Cancer Institute, Boston, MA 02215, USA; Division of Hematology/Oncology, Boston Children's Hospital, Boston, MA 02215, USA; Department of Pediatrics, Harvard Medical School, Boston, MA 02115, USA; Biological and Biomedical Sciences Program, Harvard Medical School, Boston, MA 02115, USA.
authors.forename: Katherine C
authors.initials: KC
authors.lastname: Helming
authors.affiliation: Department of Pediatric Oncology, Dana-Farber Cancer Institute, Boston, MA 02215, USA; Division of Hematology/Oncology, Boston Children's Hospital, Boston, MA 02215, USA; Department of Pediatrics, Harvard Medical School, Boston, MA 02115, USA.
authors.forename: Xiaofeng
authors.initials: X
authors.lastname: Wang
authors.affiliation: Department of Pediatric Oncology, Dana-Farber Cancer Institute, Boston, MA 02215, USA; Division of Hematology/Oncology, Boston Children's Hospital, Boston, MA 02215, USA; Department of Pediatrics, Harvard Medical School, Boston, MA 02115, USA. Electronic address: charles_roberts@dfci.harvard.edu.
authors.forename: Charles W M
authors.initials: CWM
authors.lastname: Roberts
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology / Q000627:therapeutic use; D020022:Genetic Predisposition to Disease; D006801:Humans; D058990:Molecular Targeted Therapy; D046912:Multiprotein Complexes / Q000235:genetics; D009154:Mutation; D009369:Neoplasms / Q000188:drug therapy / Q000235:genetics*; D021122:Protein Subunits / Q000235:genetics; D014157:Transcription Factors / Q000235:genetics*
chemical_list: D000970:Antineoplastic Agents; D046912:Multiprotein Complexes; D021122:Protein Subunits; D014157:Transcription Factors