title: Inactivating mutations in SWI/SNF chromatin remodeling genes in human cancer.
abstract: Chromosomal deoxyribonucleic acid and histone proteins form a highly condensed structure known as chromatin. Chromatin remodeling proteins regulate deoxyribonucleic acid transcription, synthesis and repair by changing nucleosomal composition in an adenosine triphosphate-dependent manner and mediate access of deoxyribonucleic acid-binding proteins to deoxyribonucleic acid double strands. Recently, large-scale genome sequencing studies identified somatic mutations in genes encoding chromatin remodeling proteins in a variety of human solid cancers. Notably, inactivating mutations in genes encoding the catalytic and regulatory subunits of the switch/sucrose non-fermenting chromatin remodeling complex have been detected in several solid cancers: sucrose non-fermenting/switch/sucrose non-fermenting-related, matrix-associated, actin-dependent regulator of chromatin, subfamily b, member 1/Brahma-related gene 1-associated factor 47/integrase interactor 1 mutations in rhabdoid tumors; AT-rich interactive domain-containing protein 1 A/Brahma-related gene 1-associated factor 250a mutations in ovarian clear cell carcinoma, hepatocellular carcinoma and gastric adenocarcinoma; polybromo 1/Brahma-related gene 1-associated factor 180 mutations in renal clear cell carcinoma; Brahma-related gene 1/switch/sucrose non-fermenting-related, matrix-associated, actin-dependent regulator of chromatin, subfamily a, member 4 mutations in non-small-cell lung carcinoma and AT-rich interactive domain-containing protein 2/Brahma-related gene 1-associated factor 200 mutations in hepatocellular carcinoma and malignant melanoma. This suggests that the switch/sucrose non-fermenting complex has a tumor-suppressive function, and that switch/sucrose non-fermenting gene deficiencies may affect the properties of cancer cells, which could be of value for the development of novel therapeutic strategies.
authors.affiliation: Division of Genome Biology, National Cancer Center Research Institute, 1-1, Tsukiji 5-chome, Chuo-ku, Tokyo 104-0045, Japan.
authors.forename: Takahiro
authors.initials: T
authors.lastname: Oike
authors.forename: Hideaki
authors.initials: H
authors.lastname: Ogiwara
authors.forename: Takashi
authors.initials: T
authors.lastname: Nakano
authors.forename: Jun
authors.initials: J
authors.lastname: Yokota
authors.forename: Takashi
authors.initials: T
authors.lastname: Kohno
mesh_terms: D000230:Adenocarcinoma / Q000235:genetics; D006528:Carcinoma, Hepatocellular / Q000235:genetics; D002289:Carcinoma, Non-Small-Cell Lung / Q000235:genetics; D002292:Carcinoma, Renal Cell / Q000235:genetics; D002843:Chromatin / Q000235:genetics*; D042002:Chromatin Assembly and Disassembly / Q000235:genetics*; D002868:Chromosomal Proteins, Non-Histone / Q000235:genetics*; D004265:DNA Helicases / Q000235:genetics; D004268:DNA-Binding Proteins / Q000235:genetics*; D005260:Female; D018095:Germ-Line Mutation; D006657:Histones / Q000235:genetics; D006801:Humans; D007680:Kidney Neoplasms / Q000235:genetics; D008113:Liver Neoplasms / Q000235:genetics; D008175:Lung Neoplasms / Q000235:genetics; D008545:Melanoma / Q000235:genetics; D009369:Neoplasms / Q000235:genetics*; D009687:Nuclear Proteins / Q000235:genetics; D009707:Nucleosomes / Q000235:genetics; D010051:Ovarian Neoplasms / Q000235:genetics; D000071796:SMARCB1 Protein; D012878:Skin Neoplasms / Q000235:genetics; D013274:Stomach Neoplasms / Q000235:genetics; D013329:Structure-Activity Relationship; D014157:Transcription Factors / Q000235:genetics*
chemical_list: C512511:ARID2 protein, human; D002843:Chromatin; D002868:Chromosomal Proteins, Non-Histone; D004268:DNA-Binding Proteins; D006657:Histones; D009687:Nuclear Proteins; D009707:Nucleosomes; C102195:PBRM1 protein, human; C084011:SMARCA2 protein, human; D000071796:SMARCB1 Protein; C513266:SMARCB1 protein, human; D014157:Transcription Factors; C084108:SMARCA4 protein, human; D004265:DNA Helicases
keywords: ARID1A; SWI/SNF complex; chromatin remodeling; epigenetics; inactivating mutation