Inactivating mutations in SWI/SNF chromatin remodeling genes in human cancer

• Published in: Japanese journal of clinical oncology 2013-09, Vol.43 (9), p.849-855
• Main Authors: Oike, Takahiro, Ogiwara, Hideaki, Nakano, Takashi, Yokota, Jun, Kohno, Takashi
• Format: Article
• Language: English
• Subjects: Adenocarcinoma - genetics; Carcinoma, Hepatocellular - genetics; Carcinoma, Non-Small-Cell Lung - genetics; Carcinoma, Renal Cell - genetics; Chromatin - genetics; Chromatin Assembly and Disassembly - genetics; Chromosomal Proteins, Non-Histone - genetics; DNA Helicases - genetics; DNA-Binding Proteins - genetics; Female; Germ-Line Mutation; Histones - genetics; Humans; Kidney Neoplasms - genetics; Liver Neoplasms - genetics; Lung Neoplasms - genetics; Melanoma - genetics; Neoplasms - genetics; Nuclear Proteins - genetics; Nucleosomes - genetics; Ovarian Neoplasms - genetics; Skin Neoplasms - genetics; SMARCB1 Protein; Stomach Neoplasms - genetics; Structure-Activity Relationship; Transcription Factors - genetics
• ISSN: 0368-2811; 1465-3621
• DOI: 10.1093/jjco/hyt101

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.