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Swi/snf complex

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https://www.readbyqxmd.com/read/29458976/small-cell-cancers-of-the-female-genital-tract-molecular-and-clinical-aspects
#1
REVIEW
Jay R Patibandla, Julia E Fehniger, Douglas A Levine, Petar Jelinic
OBJECTIVE: Extra-pulmonary small cell carcinomas of the gynecologic tract (EPSCC-GTs) are a rare group of aggressive malignancies associated with poor prognoses and limited treatment options. Here, we review the clinical and molecular aspects of EPSCC-GTs and discuss how understanding their molecular features can assist in their diagnosis and the identification of novel effective treatments. METHODS: We searched PubMed and Scopus for articles using the following keywords: "small cell carcinoma" in combination with "neuroendocrine", "ovary", "vagina", "fallopian tube", "vulva", "endometrium", "uterus", "cervix", or "gynecologic"...
February 17, 2018: Gynecologic Oncology
https://www.readbyqxmd.com/read/29434842/comprehensive-characterization-of-cancer-genes-in-hepatocellular-carcinoma-genomes
#2
Zhihao Zhang, Liping Xu, Changyu Sun
The present study was performed to detect moderate or low-frequency mutated cancer driver genes in hepatocellular carcinoma (HCC), using OncodriveFM and Dendrix. Following this, integrated analyses were conducted on these novel cancer driver genes. A total of 112,980 somatic mutations were retrieved from TCGA and classified into 11 categories based on their function. Driver genes and pathways were predicted by OncodriveFM and Dendrix, followed by differential expression, DNA-methylation, copy number variations and survival analyses...
February 2018: Oncology Letters
https://www.readbyqxmd.com/read/29427621/brg1-promotes-liver-fibrosis-via-activation-of-hepatic-stellate-cells
#3
Haijie Li, Jingqin Lan, Caishun Han, Kaixuan Guo, Guihua Wang, Junbo Hu, Jianping Gong, Xuelai Luo, Zhixin Cao
Liver fibrosis, an important health concern associated to chronic liver injury that provides a permissive environment for cancer development, is characterized by the persistent deposition of extracellular matrix components mainly derived from activated hepatic stellate cells (HSCs). Brg1, the core subunit of the SWI/SNF chromatin remodeling complex, has been proved to associated with nonalcoholic steatohepatitis which may progress to cirrhosis. Herein, we determined whether Brg1 regulates liver fibrosis and examined its mechanism by focusing on HSCs activation...
February 7, 2018: Experimental Cell Research
https://www.readbyqxmd.com/read/29397238/hereditary-swi-snf-complex-deficiency-syndromes
#4
REVIEW
Abbas Agaimy, William D Foulkes
The SWItch Sucrose non-fermentable (SWI/SNF) complex is a highly conserved multi-subunit complex of proteins encoded by numerous genes mapped to different chromosomal regions. The complex regulates the process of chromatin remodelling and hence plays a central role in the epigenetic regulation of gene expression, cell proliferation and differentiation. During the last three decades, the SWI/SNF complex has been increasingly recognized as a central molecular event driving the initiation and/or progression of several benign and malignant neoplasms of different anatomic origin and having diverse histomorphological appearance...
January 31, 2018: Seminars in Diagnostic Pathology
https://www.readbyqxmd.com/read/29391527/high-expression-of-smarca4-or-smarca2-is-frequently-associated-with-an-opposite-prognosis-in-cancer
#5
Jose A Guerrero-Martínez, Jose C Reyes
The gene encoding the ATPase of the chromatin remodeling SWI/SNF complexes SMARCA4 (BRG1) is often mutated or silenced in tumors, suggesting a role as tumor suppressor. Nonetheless, recent reports show requirement of SMARCA4 for tumor cells growth. Here, we performed a computational meta-analysis using gene expression, prognosis, and clinicopathological data to clarify the role of SMARCA4 and the alternative SWI/SNF ATPase SMARCA2 (BRM) in cancer. We show that while the SMARCA4 gene is mostly overexpressed in tumors, SMARCA2 is almost invariably downexpressed in tumors...
February 1, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29389935/novel-pedigree-analysis-implicates-dna-repair-and-chromatin-remodeling-in-multiple-myeloma-risk
#6
Rosalie G Waller, Todd M Darlington, Xiaomu Wei, Michael J Madsen, Alun Thomas, Karen Curtin, Hilary Coon, Venkatesh Rajamanickam, Justin Musinsky, David Jayabalan, Djordje Atanackovic, S Vincent Rajkumar, Shaji Kumar, Susan Slager, Mridu Middha, Perrine Galia, Delphine Demangel, Mohamed Salama, Vijai Joseph, James McKay, Kenneth Offit, Robert J Klein, Steven M Lipkin, Charles Dumontet, Celine M Vachon, Nicola J Camp
The high-risk pedigree (HRP) design is an established strategy to discover rare, highly-penetrant, Mendelian-like causal variants. Its success, however, in complex traits has been modest, largely due to challenges of genetic heterogeneity and complex inheritance models. We describe a HRP strategy that addresses intra-familial heterogeneity, and identifies inherited segments important for mapping regulatory risk. We apply this new Shared Genomic Segment (SGS) method in 11 extended, Utah, multiple myeloma (MM) HRPs, and subsequent exome sequencing in SGS regions of interest in 1063 MM / MGUS (monoclonal gammopathy of undetermined significance-a precursor to MM) cases and 964 controls from a jointly-called collaborative resource, including cases from the initial 11 HRPs...
February 2018: PLoS Genetics
https://www.readbyqxmd.com/read/29374542/baffling-pathologies-alterations-of-baf-complexes-in-cancer
#7
Ophelie Arnaud, François Le Loarer, Franck Tirode
To activate or repress specific genes, chromatin is constantly modified by chromatin-remodeling complexes. Among these complexes, the SWItch/Sucrose Non-Fermenting (SWI/SNF) complex, also referred to as BRG1-Associated Factor (BAF) complex, moves the nucleosome along chromatin using energy provided by ATP hydrolysis. In mammalian organisms, the SWI/SNF complex is composed of 10-15 subunits, depending on cell type, and a defect in one of these subunits can have dramatic consequences. In this review we will focus on the alterations identified in the SWI/SNF (BAF) complex subunits that lead to cancerous pathologies...
January 24, 2018: Cancer Letters
https://www.readbyqxmd.com/read/29374058/glioma-tumor-suppressor-candidate-region-gene-1-gltscr1-and-its-paralog-gltscr1-like-form-swi-snf-chromatin-remodeling-subcomplexes
#8
Aktan Alpsoy, Emily C Dykhuizen
The mammalian SWI/SNF chromatin remodeling complex is a heterogeneous collection of related protein complexes required for gene regulation and genome integrity. It contains a central ATPase (BRM or BRG1) and various combinations of 10-14 accessory subunits (BAFs for BRM/BRG1 Associated Factors). Two distinct complexes differing in size, BAF and the slightly larger Polybromo-BAF (PBAF), share many of the same core subunits but are differentiated primarily by having either AT-rich interaction domain 1A/B (ARID1A/B in BAF) or ARID2 (in PBAF)...
January 26, 2018: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/29373718/the-aberrant-splicing-of-baf45d-links-splicing-regulation-and-transcription-in-glioblastoma
#9
Guillermo Aldave, Marisol Gonzalez-Huarriz, Angel Rubio, Juan Pablo Romero, Datta Ravi, Belén Miñana, Mar Cuadrado-Tejedor, Ana García-Osta, Roeland Verhaak, Enric Xipell, Naiara Martinez-Vélez, Arlet Acanda de la Rocha, Montserrat Puigdelloses, Marc García-Moure, Miguel Marigil, Jaime Gállego Pérez-Larraya, Oskar Marín-Bejar, Maite Huarte, Maria Stella Carro, Roberto Ferrarese, Cristobal Belda-Iniesta, Angel Ayuso, Ricardo Prat-Acín, Fernando Pastor, Ricardo Díez-Valle, Sonia Tejada, Marta M Alonso
Background: Glioblastoma, the most aggressive primary brain tumor, is a genetically heterogeneous tumor. Alternative spicing (AS) plays a key role in numerous pathologies, including cancer. The objective of our study was to determine whether aberrant AS could play a role in the malignant phenotype of glioma and to understand the mechanism underlying its aberrant regulation. Methods: We obtained surgical samples from patients with glioblastoma who underwent 5-aminolevulinic fluorescence-guided surgery...
January 24, 2018: Neuro-oncology
https://www.readbyqxmd.com/read/29359803/disruption-of-mammalian-swi-snf-and-polycomb-complexes-in-human-sarcomas-mechanisms-and-therapeutic-opportunities
#10
REVIEW
Matthew J McBride, Cigall Kadoch
Soft-tissue sarcomas are increasingly characterized and subclassified by genetic abnormalities that represent underlying drivers of their pathology. Hallmark tumor suppressor gene mutations and pathognomonic gene fusions collectively account for approximately one-third of all sarcomas. These genetic abnormalities most often result in global transcriptional misregulation via disruption of protein regulatory complexes which govern chromatin architecture. Specifically, alterations to mammalian SWI/SNF (mSWI/SNF or BAF) ATP-dependent chromatin remodeling complexes and Polycomb repressive complexes cause disease-specific changes in chromatin architecture and gene expression across a number of sarcoma subtypes...
January 23, 2018: Journal of Pathology
https://www.readbyqxmd.com/read/29352111/hepatic-smarca4-predicts-hcc-recurrence-and-promotes-tumour-cell-proliferation-by-regulating-smad6-expression
#11
Zhiao Chen, Xinyuan Lu, Deshui Jia, Ying Jing, Di Chen, Qifeng Wang, Fangyu Zhao, Jinjun Li, Ming Yao, Wenming Cong, Xianghuo He
Hepatocellular carcinoma (HCC) is the most common form of liver cancer and is typically diagnosed at advanced stages. Identification and characterisation of genes within amplified and deleted chromosomal loci can provide new insights into the pathogenesis of cancer and lead to new approaches for diagnosis and therapy. In our previous study, we found a recurrent region of copy number amplification at 19p13.2 in hepatocellular carcinoma (HCC). In the present study, we performed integrated copy number analysis and expression profiling at this locus and a putative cancer gene, SMARCA4/BRG1, was uncovered in this region...
January 19, 2018: Cell Death & Disease
https://www.readbyqxmd.com/read/29352064/gif-transcriptional-co-regulators-control-root-meristem-homeostasis
#12
María Florencia Ercoli, Antonella Ferela, Juan M Debernardi, Ana Paula Perrone, Ramiro E Rodriguez, Javier Fernando Palatnik
In the root meristem, the quiescent center (QC) is surrounded by stem cells, which in turn generate the different cell types of the root. QC cells rarely divide under normal conditions but can replenish damaged stem cells. In the proximal meristem, the daughters of stem cells, which are referred to as transit amplifying cells, undergo additional rounds of cell division prior to differentiation. Here, we describe the functions of GRF-INTERACTING FACTORs (GIFs), including ANGUSTIFOLIA3 (AN3), in Arabidopsis thaliana roots...
January 18, 2018: Plant Cell
https://www.readbyqxmd.com/read/29339454/chromatin-remodeling-in-mammalian-embryos
#13
Birgit Cabot, Ryan Cabot
The mammalian embryo undergoes a dramatic amount of epigenetic remodeling during the first week of development. In this review, we discuss several epigenetic changes that happen over the course of cleavage development, focusing on covalent marks (e.g., histone methylation and acetylation) and non-covalent remodeling (chromatin remodeling via remodeling complexes ; e.g., SWI/SNF-mediated chromatin remodeling). Comparisons are also drawn between remodeling events that occur in embryos from a variety of mammalian species...
January 16, 2018: Reproduction: the Official Journal of the Society for the Study of Fertility
https://www.readbyqxmd.com/read/29334836/snf5-deficiency-induces-apoptosis-resistance-by-repressing-satb1-expression-in-s%C3%A3-zary-syndrome
#14
Yang Li, Jin Wang, Minghang Yu, Yang Wang, Huilai Zhang, Jie Yin, Zexing Li, Ting Li, Han Yan, Fajin Li, Xi Wang
SNF5, is a core member of the SWI/SNF chromatin remodeling complex. It's deficiency leads to multiple types of aggressive cancer. Sézary syndrome, a leukemic variant of cutaneous T-cell lymphoma, is characterized by its resistance to apoptosis. Although the cause of apoptosis resistance is still poorly understood, recent evidence has revealed the importance of SATB1 in the apoptosis resistance of Sézary syndrome. In this study, we show that SNF5 is an upstream regulator of SATB1 in several conditions and that both are deficient in Sézary cells...
January 16, 2018: Leukemia & Lymphoma
https://www.readbyqxmd.com/read/29309303/swi-snf-chromatin-remodeling-complex-status-in-smarcb1-ini1-preserved-epithelioid-sarcoma
#15
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...
March 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
#16
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
#17
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
#18
Deng Pan, Aya Kobayashi, Peng Jiang, Lucas Ferrari de Andrade, Rong En Tay, Adrienne M Luoma, Daphne Tsoucas, Xintao Qiu, Klothilda Lim, Prakash Rao, Henry W Long, Guo-Cheng Yuan, John Doench, Myles Brown, X 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 antitumor immunity. Inactivation of >100 genes-including Pbrm1 , Arid2 , and Brd7 , which encode components of the PBAF form of the SWI/SNF chromatin remodeling complex-sensitized mouse B16F10 melanoma cells to killing by T cells. Loss of PBAF function increased tumor cell sensitivity to interferon-γ, resulting in enhanced secretion of chemokines that recruit effector T cells...
February 16, 2018: Science
https://www.readbyqxmd.com/read/29290588/arabidopsis-argonaute-1-binds-chromatin-to-promote-gene-transcription-in-response-to-hormones-and-stresses
#19
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
#20
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
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