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https://www.readbyqxmd.com/read/29669295/a-quantitative-chemotherapy-genetic-interaction-map-reveals-factors-associated-with-parp-inhibitor-resistance
#1
Hsien-Ming Hu, Xin Zhao, Swati Kaushik, Lilliane Robillard, Antoine Barthelet, Kevin K Lin, Khyati N Shah, Andy D Simmons, Mitch Raponi, Thomas C Harding, Sourav Bandyopadhyay
Chemotherapy is used to treat most cancer patients, yet our understanding of factors that dictate response and resistance to such drugs remains limited. We report the generation of a quantitative chemical-genetic interaction map in human mammary epithelial cells charting the impact of the knockdown of 625 genes related to cancer and DNA repair on sensitivity to 29 drugs, covering all classes of chemotherapy. This quantitative map is predictive of interactions maintained in other cell lines, identifies DNA-repair factors, predicts cancer cell line responses to therapy, and prioritizes synergistic drug combinations...
April 17, 2018: Cell Reports
https://www.readbyqxmd.com/read/29669287/zranb1-is-an-ezh2-deubiquitinase-and-a-potential-therapeutic-target-in-breast-cancer
#2
Peijing Zhang, Zhenna Xiao, Shouyu Wang, Mutian Zhang, Yongkun Wei, Qinglei Hang, Jongchan Kim, Fan Yao, Cristian Rodriguez-Aguayo, Baochau N Ton, Minjung Lee, Yumeng Wang, Zhicheng Zhou, Liyong Zeng, Xiaoyu Hu, Sarah E Lawhon, Ashley N Siverly, Xiaohua Su, Jia Li, Xiaoping Xie, Xuhong Cheng, Liang-Chiu Liu, Hui-Wen Chang, Shu-Fen Chiang, Gabriel Lopez-Berestein, Anil K Sood, Junjie Chen, M James You, Shao-Cong Sun, Han Liang, Yun Huang, Xianbin Yang, Deqiang Sun, Yutong Sun, Mien-Chie Hung, Li Ma
Although EZH2 enzymatic inhibitors have shown antitumor effects in EZH2-mutated lymphoma and ARID1A-mutated ovarian cancer, many cancers do not respond because EZH2 can promote cancer independently of its histone methyltransferase activity. Here we identify ZRANB1 as the EZH2 deubiquitinase. ZRANB1 binds, deubiquitinates, and stabilizes EZH2. Depletion of ZRANB1 in breast cancer cells results in EZH2 destabilization and growth inhibition. Systemic delivery of ZRANB1 small interfering RNA (siRNA) leads to marked antitumor and antimetastatic effects in preclinical models of triple-negative breast cancer (TNBC)...
April 17, 2018: Cell Reports
https://www.readbyqxmd.com/read/29662153/author-correction-alpha-oxoglutarate-inhibits-the-proliferation-of-immortalized-normal-bladder-epithelial-cells-via-an-epigenetic-switch-involving-arid1a
#3
Muhammad Shahid, Nicole Gull, Austin Yeon, Eunho Cho, Jooeun Bae, Hyun Seok Yoon, Sungyong You, Hana Yoon, Minjung Kim, Benjamin P Berman, Jayoung Kim
A correction to this article has been published and is linked from the HTML and PDF versions of this paper. The error has been fixed in the paper.
April 16, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29660381/arid1a-ablation-leads-to-multiple-drug-resistance-in-ovarian-cancer-via-transcriptional-activation-of-mrp2
#4
Qingyu Luo, Xiaowei Wu, Yiping Zhang, Tong Shu, Fang Ding, Hongyan Chen, Pengfei Zhao, Wan Chang, Xiaolin Zhu, Zhihua Liu
Multiple Drug Resistance (MDR) of ovarian cancer is a severe trouble for clinical treatment and always attributes to a bad prognosis. AT-rich interaction domain 1 A (ARID1A) has been recognized as a bona fide tumor suppressor gene in recent years, with the highest mutation rate in ovarian cancer. Previous study illustrated that ARID1A expression is negatively correlated with chemoresistance of ovarian cancer cases. However, the specific role of ARID1A in chemoresistance of ovarian cancer remains elusive. In this study, we showed that ARID1A knockdown in ovarian cancer cells significantly reduced their apoptosis rate and led to MDR, while ectopic expression of ARID1A showed opposite effects...
April 13, 2018: Cancer Letters
https://www.readbyqxmd.com/read/29659191/optimised-arid1a-immunohistochemistry-is-an-accurate-predictor-of-arid1a-mutational-status-in-gynaecological-cancers
#5
Saira Khalique, Kalnisha Naidoo, Ayoma D Attygalle, Divya Kriplani, Frances Daley, Anne Lowe, James Campbell, Thomas Jones, Michael Hubank, Kerry Fenwick, Nicholas Matthews, Alistair G Rust, Christopher J Lord, Susana Banerjee, Rachael Natrajan
ARID1A is a tumour suppressor gene that is frequently mutated in clear cell and endometrioid carcinomas of the ovary and endometrium and is an important clinical biomarker for novel treatment approaches for patients with ARID1A defects. However, the accuracy of ARID1A immunohistochemistry (IHC) as a surrogate for mutation status has not fully been established for patient stratification in clinical trials. Here we tested whether ARID1A immunohistochemistry could reliably predict ARID1A mutations identified by next-generation sequencing...
April 16, 2018: Journal of Pathology. Clinical Research
https://www.readbyqxmd.com/read/29642667/mitochondrial-tumor-suppressor-1-mtus1-is-a-target-of-arid1a-and-progesterone-receptor-in-the-murine-uterus
#6
Hye Jin Chang, Hanna E Teasley, Jung-Yoon Yoo, Tae Hoon Kim, Jae Wook Jeong
Objective: Progesterone receptor (PGR) and ARID1A have important roles in the establishment and maintenance of pregnancy in the uterus. In present studies, we examined the expression of mitochondrial tumor suppressor 1 (MTUS1) in the murine uterus during early pregnancy as well as in response to ovarian steroid hormone treatment. Methods: We performed real-time qPCR and immunohistochemistry analysis to investigate the regulation of PIK3IP1 by ARID1A and determine expression patterns of MTUS1 in the uterus during early pregnancy...
April 12, 2018: Asian-Australasian Journal of Animal Sciences
https://www.readbyqxmd.com/read/29610389/-fgfr1-tyrosine-kinase-domain-duplication-in-pilocytic-astrocytoma-with-anaplasia
#7
Leomar Y Ballester, Marta Penas-Prado, Norman E Leeds, Jason T Huse, Gregory N Fuller
We report the case of a 27-yr-old male with visual field loss who had a 4.9-cm complex cystic mass in the right occipital lobe. Histologic examination showed pilocytic astrocytoma (PA) with anaplasia, and molecular characterization revealed FGFR1 duplication with additional variants of unknown significance in several genes ( ARID1A, ARID1B, CHEK2, EPHA5, and MLL2 ). This is one of only a very few reported cases of anaplastic PA with characterization of molecular alterations.
April 2018: Cold Spring Harbor Molecular Case Studies
https://www.readbyqxmd.com/read/29604291/arid1a-maintains-differentiation-of-pancreatic-ductal-cells-and-inhibits-development-of-pancreatic-ductal-adenocarcinoma-in-mice
#8
Yoshito Kimura, Akihisa Fukuda, Satoshi Ogawa, Takahisa Maruno, Yutaka Takada, Motoyuki Tsuda, Yukiko Hiramatsu, Osamu Araki, Munemasa Nagao, Takaaki Yoshikawa, Kozo Ikuta, Takuto Yoshioka, Zong Wang, Haruhiko Akiyama, Christopher V Wright, Kyoichi Takaori, Shinji Uemoto, Tsutomu Chiba, Hiroshi Seno
BACKGROUND & AIMS: The AT-rich interaction domain 1A gene (ARID1A) encodes a protein that is part of the large ATP-dependent chromatin remodeling complex SWI/SNF and is frequently mutated in human pancreatic ductal adenocarcinomas (PDACs). We investigated the functions of ARID1A during formation of PDACs in mice. METHODS: We performed studies with Ptf1a-Cre; KrasG12D mice, which express activated Kras in the pancreas and develop pancreatic intraepithelial neoplasias (PanINs), as well as those with disruption of Aird1a (Ptf1a-Cre; KrasG12D ; Arid1af/f mice) or disruption of Brg1 (encodes a catalytic ATPase of the SWI/SNF complex) (Ptf1a-Cre; KrasG12D ; Brg1f/f mice)...
March 28, 2018: Gastroenterology
https://www.readbyqxmd.com/read/29599905/affinity-purified-dna-based-mutation-profiles-of-endometriosis-related-ovarian-neoplasms-in-japanese-patients
#9
Masako Ishikawa, Kentaro Nakayama, Kohei Nakamura, Ruriko Ono, Kaori Sanuki, Hitomi Yamashita, Tomoka Ishibashi, Toshiko Minamoto, Kouji Iida, Sultana Razia, Noriyoshi Ishikawa, Satoru Kyo
Aim: Endometriosis-related ovarian neoplasms (ERONs) have recently attracted considerable attention; however, the prevalence and patterns of ARID1A and POLE mutations in ERONs have not been studied in detail. The aim of this study was to investigate not only the carcinogenesis of ERONs, but also the prognostic significance of several gene mutations in this cohort. We used DNA purified from only tumor epithelial cells, from which fibroblasts were removed, using a specific method we called "liquid microdissection"...
March 13, 2018: Oncotarget
https://www.readbyqxmd.com/read/29596894/pancreatic-neuroendocrine-carcinomas-reveal-a-closer-relationship-to-ductal-adenocarcinomas-than-to-neuroendocrine-tumors-g3
#10
Björn Konukiewitz, Moritz Jesinghaus, Katja Steiger, Anna Melissa Schlitter, Atsuko Kasajima, Bence Sipos, Giuseppe Zamboni, Wilko Weichert, Nicole Pfarr, Günter Klöppel
Pancreatic neuroendocrine carcinoma is a rare aggressive tumor commonly harboring TP53 and RB1 alterations and lacking neuroendocrine related genetic changes such as mutations in MEN1 and ATRX/DAXX. Little is known about its genetic profile with regard to that of pancreatic ductal adenocarcinoma. We therefore conducted a detailed genetic study in 12 pancreatic neuroendocrine carcinomas of large cell (n=9) and small cell type (n=3) using massive parallel sequencing applying a 409 gene panel on an Ion Torrent system...
March 26, 2018: Human Pathology
https://www.readbyqxmd.com/read/29590609/repurposing-pan-hdac-inhibitors-for-arid1a-mutated-ovarian-cancer
#11
Takeshi Fukumoto, Pyoung Hwa Park, Shuai Wu, Nail Fatkhutdinov, Sergey Karakashev, Timothy Nacarelli, Andrew V Kossenkov, David W Speicher, Stephanie Jean, Lin Zhang, Tian-Li Wang, Ie-Ming Shih, Jose R Conejo-Garcia, Benjamin G Bitler, Rugang Zhang
ARID1A, a subunit of the SWI/SNF complex, is among the most frequently mutated genes across cancer types. ARID1A is mutated in more than 50% of ovarian clear cell carcinomas (OCCCs), diseases that have no effective therapy. Here, we show that ARID1A mutation confers sensitivity to pan-HDAC inhibitors such as SAHA in ovarian cancers. This correlated with enhanced growth suppression induced by the inhibition of HDAC2 activity in ARID1A-mutated cells. HDAC2 interacts with EZH2 in an ARID1A status-dependent manner...
March 27, 2018: Cell Reports
https://www.readbyqxmd.com/read/29588532/molecular-changes-preceding-endometrial-and-ovarian-cancer-a-study-of-consecutive-endometrial-specimens-from-lynch-syndrome-surveillance
#12
Anni Niskakoski, Annukka Pasanen, Heini Lassus, Laura Renkonen-Sinisalo, Sippy Kaur, Jukka-Pekka Mecklin, Ralf Bützow, Päivi Peltomäki
Molecular alterations preceding endometrial and ovarian cancer and the sequence of events are unknown. Consecutive specimens from lifelong surveillance for Lynch syndrome provides a natural setting to address such questions. To molecularly define the multistep gynecological tumorigenesis, DNA mismatch repair gene mutation carriers with endometrial or ovarian carcinoma or endometrial hyperplasia were identified from a nation-wide registry and endometrial biopsy specimens taken from these individuals during 20 years of screening were collected...
March 27, 2018: Modern Pathology: An Official Journal of the United States and Canadian Academy of Pathology, Inc
https://www.readbyqxmd.com/read/29581767/inhibition-of-pi3k-akt-signaling-pathway-radiosensitizes-pancreatic-cancer-cells-with-arid1a-deficiency-in-vitro
#13
Lin Yang, Guanghai Yang, Yingjun Ding, Yuhong Dai, Sanpeng Xu, Qiuyun Guo, Aini Xie, Guangyuan Hu
Pancreatic cancer is among the most aggressive human cancers, and is resistant to regular chemotherapy and radiotherapy. The AT-rich interactive domain containing protein 1A ( ARID1A ) gene, a crucial chromatin remodeling gene, mutates frequently in a broad spectrum of cancers, including pancreatic cancer. Recent evidence suggests that ARID1A acts as tumor suppressor and plays an important role in DNA damage repair (DDR). However, the effect of ARID1A on the radiosensitivity of pancreatic cancer remains unclear...
2018: Journal of Cancer
https://www.readbyqxmd.com/read/29573058/molecular-genomic-landscapes-of-hepatobiliary-cancer
#14
REVIEW
Tatsuhiro Shibata, Yasuhito Arai, Yasushi Totoki
Hepatocellular carcinoma (HCC) and biliary tract cancer (BTC) are more frequent in East Asia including Japan. Compiling 1,340 multi-ethnic HCC genomes, the largest cohort ever reported, identified comprehensive landscape of HCC driver genes, which constitutes three core drivers (TP53, TERT and WNT signaling) and combination of infrequent alterations in various cancer pathways. By contrast, five core driver genes (TP53, ARID1A, KRAS, SMAD4 and BAP1) with characteristic molecular alterations including fusion transcripts involving FGFR2 and the PKA pathway, and IDH1/2 mutation constituted the BTC genomes...
March 23, 2018: Cancer Science
https://www.readbyqxmd.com/read/29571084/comprehensive-analysis-of-cancers-of-unknown-primary-for-the-biomarkers-of-response-to-immune-checkpoint-blockade-therapy
#15
Zoran Gatalica, Joanne Xiu, Jeff Swensen, Semir Vranic
BACKGROUND: Cancer of unknown primary (CUP) accounts for approximately 3% of all malignancies. Avoiding immune destruction is a major cancer characteristic and therapies aimed at immune checkpoint blockade are in use for several specific cancer types. A comprehensive survey of predictive biomarkers to immune checkpoint blockade in CUP were explored in this study. METHODS: About 389 cases of CUP were analysed for mutations in 592 genes and 52 gene fusions using a massively parallel DNA sequencing platform (next-generation sequencing [NGS])...
March 20, 2018: European Journal of Cancer
https://www.readbyqxmd.com/read/29555573/whole-exome-sequencing-identified-mutational-profiles-of-squamous-cell-carcinomas-of-anus
#16
Sun Shin, Hyeon-Chun Park, Min Sung Kim, Mi-Ryung Han, Sung Hak Lee, Seung Hyun Jung, Sug Hyung Lee, Yeun-Jun Chung
Anal squamous cell carcinoma (ASCC), either with human papillomavirus (HPV) (+) or (-), is a neoplastic disease with frequent recurrence and metastasis. To characterize ASCC genomes, we attempted to disclose novel alterations of ASCC genomes as well as other genetic features including mutation signatures. We performed whole-exome sequencing and copy number alteration (CNA) profiling for 8 ASCC samples from 6 patients (2 cases with primary and recurrent/metastatic tumors). We found known ASCC mutations (TP53, CDKN2A and PIK3CA) and CNAs (gains on 3q and 19q and losses on 11q and 13q)...
March 16, 2018: Human Pathology
https://www.readbyqxmd.com/read/29547736/the-presence-of-kras-ppp2r1a-and-arid1a-mutations-in-101-chinese-samples-with-ovarian-endometriosis
#17
Yang Zou, Jiang-Yan Zhou, Jiu-Bai Guo, Li-Qun Wang, Yong Luo, Zi-Yu Zhang, Fa-Ying Liu, Jun Tan, Feng Wang, Ou-Ping Huang
Endometriosis is a potential premalignant disorder. The underlying molecular aberrations, however, are not fully understood. A recent exome sequencing study found that 25% (10/39) of deep infiltrating endometriosis harbored cancer driver gene mutations. However, it is unclear whether these mutations also exist in ovarian endometriosis. Here, a total of 101 ovarian endometriosis samples were analyzed for the presence of these gene mutations, including KRAS, PPP2R1A, PIK3CA and ARID1A. In addition, 6 other cancer-associated genes (BRAF, NRAS, HRAS, ERK1, ERK2 and PTEN) were also analyzed...
March 9, 2018: Mutation Research
https://www.readbyqxmd.com/read/29540744/alpha-oxoglutarate-inhibits-the-proliferation-of-immortalized-normal-bladder-epithelial-cells-via-an-epigenetic-switch-involving-arid1a
#18
Muhammad Shahid, Nicole Gull, Austin Yeon, Eunho Cho, Jooeun Bae, Hyun Seok Yoon, Sungyong You, Hana Yoon, Minjung Kim, Benjamin P Berman, Jayoung Kim
Interstitial cystitis (IC) is a chronic urinary tract disease that is characterized by unpleasant sensations, such as persistent pelvic pain, in the absence of infection or other identifiable causes. We previously performed comprehensive metabolomics profiling of urine samples from IC patients using nuclear magnetic resonance and gas-chromatography/mass spectrometry and found that urinary α-oxoglutarate (α-OG), was significantly elevated. α-OG, a tricarboxylic acid (TCA) cycle intermediate, reportedly functions to suppress the proliferation of immortalized normal human bladder epithelial cells...
March 14, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29517810/characterization-of-metastatic-urothelial-carcinoma-via-comprehensive-genomic-profiling-of-circulating-tumor-dna
#19
Neeraj Agarwal, Sumanta K Pal, Andrew W Hahn, Roberto H Nussenzveig, Gregory R Pond, Sumati V Gupta, Jue Wang, Mehmet A Bilen, Gurudatta Naik, Pooja Ghatalia, Christopher J Hoimes, Dharmesh Gopalakrishnan, Pedro C Barata, Alexandra Drakaki, Bishoy M Faltas, Lesli A Kiedrowski, Richard B Lanman, Rebecca J Nagy, Nicholas J Vogelzang, Kenneth M Boucher, Ulka N Vaishampayan, Guru Sonpavde, Petros Grivas
BACKGROUND: Biomarker-guided clinical trials are increasingly common in metastatic urothelial carcinoma (mUC), yet patients for whom contemporary tumor tissue is not available are not eligible. Technological advancements in sequencing have made cell-free circulating DNA (cfDNA) next-generation sequencing (NGS) readily available in the clinic. The objective of the current study was to determine whether the genomic profile of mUC detected by NGS of cfDNA is similar to historical tumor tissue NGS studies...
March 8, 2018: Cancer
https://www.readbyqxmd.com/read/29500370/common-variants-of-arid1a-and-kat2b-are-associated-with-obesity-in-indian-adolescents
#20
Anil K Giri, Vaisak Parekatt, Om Prakash Dwivedi, Priyanka Banerjee, Khushdeep Bandesh, Gauri Prasad, Nikhil Tandon, Dwaipayan Bharadwaj
Obesity involves alterations in transcriptional programs that can change in response to genetic and environmental signals through chromatin modifications. Since chromatin modifications involve different biochemical, neurological and molecular signaling pathways related to energy homeostasis, we hypothesize that genetic variations in chromatin modifier genes can predispose to obesity. Here, we assessed the associations between 179 variants in 35 chromatin modifier genes and overweight/obesity in 1283 adolescents (830 normal weight and 453 overweight/obese)...
March 2, 2018: Scientific Reports
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