Anti-SMARCC2 (C-terminal) polyclonal antibody

The switching defective/sucrose nonfermenting (SWI/SNF) related, matrix associated, actin dependent regulators of chromatin (SMARC) are components of human SWI/SNF like chromatin remodeling protein complexes, which are essential in the process of DNA damage repair. In this study, we hypothesized that genetic variants in SMARC genes may modify the capacity of DNA repair to damage. To test this hypothesis, we genotyped a total of 20 polymorphisms in five key SMARC genes (SMARCA5, SMARCC2, SMARCD1, SMARCD2, SMARCD3) to evaluate their associations with DNA damage levels in 307 subjects. The DNA damage levels were measured with comet assay. The multiple linear regression was used to assess the relationship between each polymorphism and DNA damage levels in additive model. We found that the genotypes of rs6857360 (beta = 0.23, 95% CI = 0.06-0.40, P = 0.008) in SMARCA5, rs6919 (beta = 0.20, 95% CI = 0.05-0.34, P = 0.008) and rs2727280 (beta = 0.18, 95% CI = 0.04-0.33, P = 0.013) in SMARCD2, and rs17173769 (beta = -0.27, 95% CI = -0.52 to -0.01, P = 0.045) in SMARCD3 were significantly associated with DNA damage levels. After combining these four polymorphisms, we found that the more unfavorable alleles the subjects carried, the heavier DNA damage they suffered, suggesting a locus-dosage effect between combined genotypes and DNA damage levels (P for trend = 0.006). These findings suggest that genetic variants in SMARC genes may contribute the individual variations of DNA damage levels in Chinese population. Further larger and functional studies are warranted to confirm our findings. (C) 2014 Elsevier Ireland Ltd. All rights reserved.

Loss of the SWI/SNF chromatin remodeling complex has been recently implicated in the pathogenesis of dedifferentiated carcinomas from different organs, but its possible role in undifferentiated urothelial carcinoma (UC) has not been studied to date. In this study, we analyzed by immunohistochemistry 14 undifferentiated UCs (11 from bladder and 3 from renal pelvis) with a nondescript anaplastic or rhabdoid morphology, using commercially available antibodies against the SWI/SNF components SMARCB1 (INI1), SMARCA2, SMARCA4, SMARCC1, SMARCC2, and ARID1A. Patients were eight females and six males aged 40 to 84 years (median, 65). All tumors were muscle-invasive (9 were T3-4). A conventional UC component was seen in eight cases and varied from in situ to papillary. The undifferentiated component comprised 60-100 % of the tumors. Histologically, most tumors showed diffuse dyscohesive or pseudoalveolar growth of variably sized cells with frequent rhabdoid features. Transition from conventional to undifferentiated UC was abrupt, except in one case. The undifferentiated component almost always expressed pan-cytokeratin AE1/AE3 (13/14) and variably vimentin (8/14) and GATA3 (9/14). Complete loss of at least one SWI/SNF subunit limited to the undifferentiated component was detected in 10/14 cases (71 %). SMARCA2 was most frequently lost (six) followed by ARID1A (four), SMARCB1/INI1 (two), SMARCA4 (one), and SMARCC1 (one). This is the first study exploring SWI/SNF expression in undifferentiated UC of the urinary tract. Our results are in line with recent studies reporting involvement of the SWI/SNF complex in the dedifferentiation process of a variety of epithelial neoplasms in different organs, including the urinary tract, and association with aggressive clinical course.