title: [Chromatin remodeling defects and cancer: the SWI/SNF example].
abstract: The SWI/SNF complex is a multiprotein complex essential for chromatin remodelling. As such, it plays a key role in the epigenetic regulation of genome expression. This complex is composed of a dozen of proteins, some of which are constant and ubiquitous, especially SMARCB1 and SMARCA4. Mutations in these genes are now described in an increasing number of tumors. Mutations in SMARCB1 characterize the majority of rhabdoid tumors, an aggressive malignancy that exquisitely depends on this single genetic event. Rare rhabdoid tumors have mutation in SMARCA4, a genetic abnormality also found in some medulloblastomas. Many other tumor types, of variable aggressiveness, show an abnormal loss of expression of SMARCB1, but the genetic underlying cause most often remains elusive. The recent sequencings of whole exomes have described frequent mutations in other genes of the SWI/SNF complex: mutations in ARID1A in liver, gastric or bladder carcinomas, and PBRM1 mutations in renal cancers. These data establish the wide role of SWI/SNF complex in cancers and justify that major efforts should now be devoted to this common mechanism of human oncogenesis.
authors.affiliation: Institut Curie, département d'oncologie pédiatrique, Inserm U830-laboratoire de génétique et biologie des cancers, 26, rue d'Ulm, 75248 Paris Cedex 05, France. Franck.Bourdeaut@curie.fr
authors.forename: Franck
authors.initials: F
authors.lastname: Bourdeaut
authors.forename: Ivan
authors.initials: I
authors.lastname: Bièche
mesh_terms: D042002:Chromatin Assembly and Disassembly / Q000235:genetics*; D002868:Chromosomal Proteins, Non-Histone / Q000172:deficiency / Q000235:genetics*; D004265:DNA Helicases / Q000235:genetics*; D004268:DNA-Binding Proteins / Q000172:deficiency / Q000235:genetics*; D006801:Humans; D008527:Medulloblastoma / Q000235:genetics; D008579:Meningioma / Q000235:genetics; D009369:Neoplasms / Q000235:genetics*; D009442:Neurilemmoma / Q000235:genetics; D009687:Nuclear Proteins / Q000235:genetics*; D018335:Rhabdoid Tumor / Q000235:genetics; D000071796:SMARCB1 Protein; D012509:Sarcoma / Q000235:genetics; D014157:Transcription Factors / Q000172:deficiency / Q000235:genetics*
chemical_list: C112476:ARID1A protein, human; C497837:ARID1B protein, human; C512511:ARID2 protein, human; D002868:Chromosomal Proteins, Non-Histone; D004268:DNA-Binding Proteins; D009687:Nuclear Proteins; C084011:SMARCA2 protein, human; D000071796:SMARCB1 Protein; C513266:SMARCB1 protein, human; D014157:Transcription Factors; C084108:SMARCA4 protein, human; D004265:DNA Helicases