Division of Genome Biology, National Cancer Center Research Institute, 1-1, Tsukiji 5-chome, Chuo-ku, Tokyo 104-0045, Japan.
Jpn J Clin Oncol. 2013 Sep;43(9):849-55. doi: 10.1093/jjco/hyt101. Epub 2013 Jul 30.
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.
染色质由脱氧核糖核酸和组蛋白形成一种高度浓缩的结构。染色质重塑蛋白通过改变核小体组成的方式，以三磷酸腺苷依赖的方式调节脱氧核糖核酸转录、合成和修复，并介导脱氧核糖核酸结合蛋白对脱氧核糖核酸双链的访问。最近，大规模基因组测序研究鉴定出多种人类实体瘤中编码染色质重塑蛋白的基因发生体细胞突变。值得注意的是，在几种实体瘤中检测到编码开关/蔗糖非发酵染色质重塑复合物催化亚基和调节亚基的基因失活突变：在横纹肌肉瘤中检测到蔗糖非发酵/开关/蔗糖非发酵相关、基质相关、肌动蛋白依赖性染色质调节剂亚家族 b、成员 1/BRG1 相关基因 1 相关因子 47/整合酶相互作用因子 1 突变；在卵巢透明细胞癌、肝细胞癌和胃腺癌中检测到富含 AT 相互作用域蛋白 1/BRG1 相关基因 1 相关因子 250a 突变；在肾透明细胞癌中检测到多溴 1/BRG1 相关基因 1 相关因子 180 突变；在非小细胞肺癌中检测到 BRG1/开关/蔗糖非发酵相关、基质相关、肌动蛋白依赖性染色质调节剂亚家族 a、成员 4 突变；在肝细胞癌和恶性黑色素瘤中检测到富含 AT 相互作用域蛋白 2/BRG1 相关基因 1 相关因子 200 突变。这表明开关/蔗糖非发酵复合物具有肿瘤抑制功能，而开关/蔗糖非发酵基因缺失可能影响癌细胞的特性，这可能对开发新的治疗策略具有价值。
