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https://www.readbyqxmd.com/read/29309303/swi-snf-chromatin-remodeling-complex-status-in-smarcb1-ini1-preserved-epithelioid-sarcoma
#1
Kenichi Kohashi, Hidetaka Yamamoto, Yuichi Yamada, Izumi Kinoshita, Tomoaki Taguchi, Yukihide Iwamoto, Yoshinao Oda
The SWI/SNF chromatin-remodeling complex, which is composed of evolutionarily conserved core subunits such as SMARCB1/INI1 (INI1), SMARCA4/BRG1 (BRG1), SMARCC1/BAF155 (BAF155), and SMARCC2/BAF170 (BAF170), can be viewed as the prototype of an epigenetic regulator of gene expression that is involved in tumor suppression. Epithelioid sarcoma, which classified as a tumor of uncertain differentiation, shows an almost complete loss of INI1. However, some cases of epithelioid sarcoma have preserved INI1, and the clinicopathologic features of these cases are uncertain...
January 5, 2018: American Journal of Surgical Pathology
https://www.readbyqxmd.com/read/29307627/dedifferentiated-liposarcoma-composed-predominantly-of-rhabdoid-epithelioid-cells-a-frequently-misdiagnosed-highly-aggressive-variant
#2
Abbas Agaimy, Michael Michal, Ladislav Hadravsky, Michal Michal
Dedifferentiated liposarcoma is one of the most common sarcoma types in adults with a predilection for the retroperitoneum. We have recently encountered 6 cases of DDL composed predominantly of rounded, rhabdoid or epithelioid cells mimicking rhabdoid melanoma, epithelioid rhabdomyosarcoma or undifferentiated carcinoma. Patients were 5 males and one female aged 64 to 81 years (median, 68). Tumors originated in the retroperitoneum (n=5; 3 in the psoas muscle) and deep soft tissue of the thigh (n=1). All 3 patients with follow-up died of metastatic disease within 4 to 8 months...
January 4, 2018: Human Pathology
https://www.readbyqxmd.com/read/29301960/genomic-correlates-of-response-to-immune-checkpoint-therapies-in-clear-cell-renal-cell-carcinoma
#3
Diana Miao, Claire A Margolis, Wenhua Gao, Martin H Voss, Wei Li, Dylan J Martini, Craig Norton, Dominick Bossé, Stephanie M Wankowicz, Dana Cullen, Christine Horak, Megan Wind-Rotolo, Adam Tracy, Marios Giannakis, Frank Stephen Hodi, Charles G Drake, Mark W Ball, Mohamad E Allaf, Alexandra Snyder, Matthew D Hellmann, Thai Ho, Robert J Motzer, Sabina Signoretti, William G Kaelin, Toni K Choueiri, Eliezer M Van Allen
Immune checkpoint inhibitors targeting the programmed cell death-1 receptor (PD-1) improve survival in a subset of patients with clear cell renal cell carcinoma (ccRCC). To identify genomic alterations in ccRCC that correlate with response to anti-PD-1 monotherapy, we performed whole exome sequencing of metastatic ccRCC from 35 patients. We found that clinical benefit was associated with loss-of-function mutations in the PBRM1 gene (p=0.012), which encodes a subunit of a SWI/SNF chromatin remodeling complex (the PBAF subtype)...
January 4, 2018: Science
https://www.readbyqxmd.com/read/29301958/a-major-chromatin-regulator-determines-resistance-of-tumor-cells-to-t-cell-mediated-killing
#4
Deng Pan, Aya Kobayashi, Peng Jiang, Lucas Ferrari de Andrade, Rong En Tay, Adrienne Luoma, Daphne Tsoucas, Xintao Qiu, Klothilda Lim, Prakash Rao, Henry W Long, Guo-Cheng Yuan, John Doench, Myles Brown, Shirley Liu, Kai W Wucherpfennig
Many human cancers are resistant to immunotherapy for reasons that are poorly understood. We used a genome-scale CRISPR/Cas9 screen to identify mechanisms of tumor cell resistance to killing by cytotoxic T cells, the central effectors of anti-tumor immunity. Inactivation of >100 genes sensitized mouse B16F10 melanoma cells to killing by T cells, including Pbrm1, Arid2 and Brd7, which encode components of the PBAF form of the SWI/SNF chromatin remodeling complex. Loss of PBAF function increased tumor cell sensitivity to interferon-γ, resulting in enhanced secretion of chemokines that recruit effector T cells...
January 4, 2018: Science
https://www.readbyqxmd.com/read/29290588/arabidopsis-argonaute-1-binds-chromatin-to-promote-gene-transcription-in-response-to-hormones-and-stresses
#5
Chang Liu, Ying Xin, Le Xu, Zhaokui Cai, Yuanchao Xue, Yong Liu, Daoxin Xie, Yule Liu, Yijun Qi
Conventional RNA interference (RNAi) pathways suppress eukaryotic gene expression at the transcriptional or post-transcriptional level. At the core of RNAi are small RNAs (sRNAs) and effector Argonaute (AGO) proteins. Arabidopsis AGO1 is known to bind microRNAs (miRNAs) and post-transcriptionally repress target genes in the cytoplasm. Here, we report that AGO1 also binds to the chromatin of active genes and promotes their transcription. We show that sRNAs and SWI/SNF complexes associate with nuclear AGO1 and are required for AGO1 binding to chromatin...
December 27, 2017: Developmental Cell
https://www.readbyqxmd.com/read/29280680/smarcb1-deficient-tumors-of-childhood-a-practical-guide
#6
Bruce R Pawel
The SMARCB1 gene ( INI1, BAF47) is a member of the SWItch/Sucrose Non-Fermentable (SWI/SNF) chromatin remodeling complex, involved in the epigenetic regulation of gene transcription. SMARCB1 acts as a tumor suppressor gene, and loss of function of both alleles gives rise to SMARCB1-deficient tumors. The prototypical SMARCB1-deficient tumor is the malignant rhabdoid tumor (MRT) which was first described in the kidney but also occurs in soft tissue, viscera, and the brain (where it is referred to as atypical teratoid rhabdoid tumor or AT/RT)...
January 1, 2017: Pediatric and Developmental Pathology
https://www.readbyqxmd.com/read/29273066/co-regulation-of-transcription-by-brg1-and-brm-two-mutually-exclusive-swi-snf-atpase-subunits
#7
Jesse R Raab, John S Runge, Camarie C Spear, Terry Magnuson
BACKGROUND: SWI/SNF is a large heterogeneous multi-subunit chromatin remodeling complex. It consists of multiple sets of mutually exclusive components. Understanding how loss of one sibling of a mutually exclusive pair affects the occupancy and function of the remaining complex is needed to understand how mutations in a particular subunit might affect tumor formation. Recently, we showed that the members of the ARID family of SWI/SNF subunits (ARID1A, ARID1B and ARID2) had complex transcriptional relationships including both antagonism and cooperativity...
December 22, 2017: Epigenetics & Chromatin
https://www.readbyqxmd.com/read/29220290/synovial-sarcoma-current-concepts-and-future-perspectives
#8
Silvia Stacchiotti, Brian Andrew Van Tine
Synovial sarcoma (SS) is a rare sarcoma driven by a translocation between SS18 and SSX 1, 2, or 4. With approximately 800 to 1,000 cases a year in the United States, it most commonly affects young adults between the ages of 15 and 30 years. The resultant tumors are either monophasic (pure sarcomas), biphasic (a combination or epithelioid and sarcomatous components), or poorly differentiated. The hybrid transcription factor SS18:SSX alters SWItch/Sucrose Non-Fermentable (SWI/SNF) chromatin remodeling and global methylation patterns that may allow for future therapeutic opportunities...
December 8, 2017: Journal of Clinical Oncology: Official Journal of the American Society of Clinical Oncology
https://www.readbyqxmd.com/read/29218250/evaluation-of-the-role-of-downregulation-of-snf5-ini1-core-subunit-of-swi-snf-complex-in-clear-cell-renal-cell-carcinoma-development
#9
Elzbieta Sarnowska, Michal Szymanski, Nataliia Rusetska, Marcin Ligaj, Iga Jancewicz, Pawel Cwiek, Marta Skrodzka, Marcin Leszczynski, Joanna Szarkowska, Alicja Chrzan, Malgorzata Stachowiak, Jaroslaw Steciuk, Anna Maassen, Lech Galek, Tomasz Demkow, Janusz A Siedlecki, Tomasz J Sarnowski
Clear cell renal cell carcinoma (ccRCC) is characterized by stabilization of hypoxia-inducible factor (HIF1), and mutations in von Hippel-Lindau (VHL) gene. Additionally, in about 40% of ccRCC cases the mutation in PBRM1 (POLYBROMO1) gene coding for a non-core subunit of SWI/SNF chromatin remodeling complex was found suggesting potential impairment of this complex function in ccRCC. In this study we assessed the extent to which the core SWI/SNF complex subunit - INI1 (hSNF5/SMARCB1) is affected in ccRCC and whether it has any consequences on the development of this type of cancer...
2017: American Journal of Cancer Research
https://www.readbyqxmd.com/read/29213114/the-swi-snf-subunit-bcl7a-contributes-to-motor-coordination-and-purkinje-cell-function
#10
Lena Wischhof, Simona Maida, Antonia Piazzesi, Anna Gioran, Kristina Barragan Sanz, Stephan Irsen, Marc Beyer, Joachim L Schultze, Martin J Dyer, Paolo Salomoni, Dan Ehninger, Pierluigi Nicotera, Daniele Bano
Chromatin remodelers have emerged as prominent regulators of epigenetic processes and potential drivers of various human pathologies. The multi-subunit chromatin-remodeling SWI/SNF complex determines gene expression programs and, consequently, contributes to the differentiation, maturation and plasticity of neurons. Here, we investigate the elusive biological function of Bcl7a and Bcl7b, two newly identified subunits of the SWI/SNF complex that are highly expressed throughout the brain. We generated ubiquitous and neuron-specific Bcl7a and Bcl7b single and double knockout mice...
December 6, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29183906/cardiac-enriched-baf-chromatin-remodeling-complex-subunit-baf60c-regulates-gene-expression-programs-essential-for-heart-development-and-function
#11
Xin Sun, Swetansu K Hota, Yu-Qing Zhou, Stefanie Novak, Dario Miguel-Perez, Danos Christodoulou, Christine E Seidman, J G Seidman, Carol C Gregorio, R Mark Henkelman, Janet Rossant, Benoit G Bruneau
How chromatin-remodeling complexes modulate gene networks to control organ-specific properties is not well understood. For example, Baf60c (Smarcd3) encodes a cardiac-enriched subunit of the SWI/SNF-like BAF chromatin complex, but its role in heart development is not fully understood. We found that constitutive loss of Baf60c leads to embryonic cardiac hypoplasia and pronounced cardiac dysfunction. Conditional deletion of Baf60c in cardiomyocytes resulted in postnatal dilated cardiomyopathy with impaired contractile function...
November 28, 2017: Biology Open
https://www.readbyqxmd.com/read/29178559/arid1a-a-component-of-swi-snf-chromatin-remodeling-complexes-is-required-for-porcine-embryo-development
#12
Yu-Chun Tseng, Birgit Cabot, Ryan A Cabot
Mammalian embryos undergo dramatic epigenetic remodeling that can have a profound impact on both gene transcription and overall embryo developmental competence. Members of the SWI/SNF (Switch/Sucrose non-fermentable) family of chromatin-remodeling complexes reposition nucleosomes and alter transcription factor accessibility. These large, multi-protein complexes possess an SNF2-type ATPase (either SMARCA4 or SMARCA2) as their core catalytic subunit, and are directed to specific loci by associated subunits. Little is known about the identity of specific SWI/SNF complexes that serve regulatory roles during cleavage development...
November 26, 2017: Molecular Reproduction and Development
https://www.readbyqxmd.com/read/29156698/combined-brd4-and-cdk9-inhibition-as-a-new-therapeutic-approach-in-malignant-rhabdoid-tumors
#13
Natalia Moreno, Till Holsten, Julius Mertins, Annabelle Zhogbi, Pascal Johann, Marcel Kool, Michael Meisterernst, Kornelius Kerl
Rhabdoid tumors are caused by the deletion of SMARCB1, whose protein encodes the SMARCB1 subunit of the chromatin remodeling complex SWI/SNF that is involved in global chromatin organization and gene expression control. Simultaneously inhibiting the main players involved in the deregulated transcription machinery is a promising option for preventing exaggerated tumor cell proliferation and survival as it may bypass compensatory mechanisms. In support of this hypothesis, we report efficient impairment of cellular proliferation and strong induction of cell death elicited by inhibition of bromodomain protein BRD4 and transcription kinase CDK9 using small molecular compounds...
October 17, 2017: Oncotarget
https://www.readbyqxmd.com/read/29152582/the-genomic-landscape-of-the-fungus-specific-swi-snf-complex-subunit-snf6-in-candida-albicans
#14
Faiza Tebbji, Yaolin Chen, Adnane Sellam, Malcolm Whiteway
SWI/SNF is an ATP-dependent chromatin-remodeling complex that is required for the regulation of gene expression in eukaryotes. While most of the fungal SWI/SNF components are evolutionarily conserved with those of the metazoan SWI/SNF, subunits such as Snf6 are specific to certain fungi and thus represent potential antifungal targets. We have characterized the role of the Snf6 protein in Candida albicans. Our data showed that although there was low conservation of its protein sequence with other fungal orthologs, Snf6 was copurified with bona fide SWI/SNF complex subunits...
November 2017: MSphere
https://www.readbyqxmd.com/read/29151933/expression-of-arid1b-is-associated-with-poor-outcomes-and-predicts-the-benefit-from-adjuvant-chemotherapy-in-bladder-urothelial-carcinoma
#15
Beihe Wang, Huyang Xie, Chunguang Ma, Guiming Zhang, Hualei Gan, Qifeng Wang, Xiaohang Liu, Yiping Zhu, Yao Zhu, Guohai Shi, Hailiang Zhang, Bo Dai, Yijun Shen, Dingwei Ye
Background ARID1B, which exists as a mutually exclusive isoform with ARID1A in the SWI/SNF chromatin remodeling complex, has been recently identified as a major mutant gene in a wide variety of cancers. The present study aimed to determine the association between ARID1B expression and outcomes, as well as the benefit from adjuvant chemotherapy in patients with bladder cancer. Methods Tissue microarrays of 143 consecutively recruited patients with bladder cancer from our center were created. Immunohistochemistry was performed to assess the expression of ARID1B and its association with outcomes...
2017: Journal of Cancer
https://www.readbyqxmd.com/read/29138824/genetic-mutational-testing-of-chinese-children-with-familial-hematuria-with-biopsy%C3%A2-proven-fsgs
#16
Yongzhen Li, Ying Wang, Qingnan He, Xiqiang Dang, Yan Cao, Xiaochuan Wu, Shuanghong Mo, Xiaoxie He, Zhuwen Yi
Focal segmental glomerulosclerosis (FSGS) is a pathological lesion rather than a disease, with a diverse etiology. FSGS may result from genetic and non‑genetic factors. FSGS is considered a podocyte disease due to the fact that in the majority of patients with proven‑FSGS, the lesion results from defects in the podocyte structure or function. However, FSGS does not result exclusively from podocyte‑associated genes, however also from other genes including collagen IV‑associated genes. Patients who carry the collagen type IVA3 chain (COL4A3) or COL4A4 mutations usually exhibit Alport Syndrome (AS), thin basement membrane neuropathy or familial hematuria (FH)...
November 10, 2017: Molecular Medicine Reports
https://www.readbyqxmd.com/read/29136504/arid1a-has-context-dependent-oncogenic-and-tumor-suppressor-functions-in-liver-cancer
#17
Xuxu Sun, Sam C Wang, Yonglong Wei, Xin Luo, Yuemeng Jia, Lin Li, Purva Gopal, Min Zhu, Ibrahim Nassour, Jen-Chieh Chuang, Thomas Maples, Cemre Celen, Liem H Nguyen, Linwei Wu, Shunjun Fu, Weiping Li, Lijian Hui, Feng Tian, Yuan Ji, Shuyuan Zhang, Mahsa Sorouri, Tae Hyun Hwang, Lynda Letzig, Laura James, Zixi Wang, Adam C Yopp, Amit G Singal, Hao Zhu
ARID1A, an SWI/SNF chromatin-remodeling gene, is commonly mutated in cancer and hypothesized to be tumor suppressive. In some hepatocellular carcinoma patients, ARID1A was highly expressed in primary tumors but not in metastatic lesions, suggesting that ARID1A can be lost after initiation. Mice with liver-specific homozygous or heterozygous Arid1a loss were resistant to tumor initiation while ARID1A overexpression accelerated initiation. In contrast, homozygous or heterozygous Arid1a loss in established tumors accelerated progression and metastasis...
November 13, 2017: Cancer Cell
https://www.readbyqxmd.com/read/29136498/a-two-faced-mswi-snf-subunit-dual-roles-for-arid1a-in-tumor-suppression-and-oncogenicity-in-the-liver
#18
Jordan E Otto, Cigall Kadoch
In this issue of Cancer Cell, Sun et al. describe context-dependent oncogenic and tumor-suppressive functions for the mammalian SWI/SNF (BAF) complex subunit ARID1A in the development and progression of hepatocellular carcinoma (HCC).
November 13, 2017: Cancer Cell
https://www.readbyqxmd.com/read/29092888/uncoupling-exercise-bioenergetics-from-systemic-metabolic-homeostasis-by-conditional-inactivation-of-baf60-in-skeletal-muscle
#19
Zhuo-Xian Meng, Weiwei Tao, Jingxia Sun, Qiuyu Wang, Lin Mi, Jiandie D Lin
Impaired skeletal muscle energy metabolism is linked to the pathogenesis of insulin resistance and glucose intolerance in type 2 diabetes. The contractile and metabolic properties of myofibers exhibit a high degree of heterogeneity and plasticity. The regulatory circuitry underpinning skeletal muscle energy metabolism is critically linked to exercise endurance and systemic homeostasis. Recent work has identified the Baf60 subunits of the SWI/SNF chromatin-remodeling complex as powerful regulators of the metabolic gene programs...
November 1, 2017: Diabetes
https://www.readbyqxmd.com/read/29079174/mir-223-potentially-targets-swi-snf-complex-protein-smarcd1-in-atypical-proliferative-serous-tumor-and-high-grade-ovarian-serous-carcinoma
#20
Florence A Arts, Lisa Keogh, Paul Smyth, Sharon O'Toole, Robert Ta, Noreen Gleeson, John J O'Leary, Richard Flavin, Orla Sheils
Ovarian cancer is the fifth most common cancer in women worldwide and has the highest mortality amongst gynecological cancers. miRNAs are a class of non-coding RNAs, approximately 22 nt long, that negatively regulate gene expression and to have roles in cell growth, differentiation, metabolism, apoptosis and tumorigenesis. Dysregulated miRNA-223 expression has been implicated in a wide range of cancer subtypes. SMARCD1 is an integral protein component of the SWI/SNF complex which remodels chromatin, and which has important roles in transcriptional control, DNA replication, recombination and repair...
October 24, 2017: Human Pathology
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