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https://www.readbyqxmd.com/read/29435122/apobec-mediated-mutagenesis-in-urothelial-carcinoma-is-associated-with-improved-survival-mutations-in-dna-damage-response-genes-and-immune-response
#1
Alexander P Glaser, Damiano Fantini, Yiduo Wang, Yanni Yu, Kalen J Rimar, Joseph R Podojil, Stephen D Miller, Joshua J Meeks
APOBEC enzymes are responsible for a mutation signature (TCW>T/G) implicated in a wide variety of tumors. We explore the APOBEC mutational signature in bladder cancer and the relationship with specific mutations, molecular subtype, gene expression, and survival using sequencing data from The Cancer Genome Atlas (n = 395), Beijing Genomics Institute (n = 99), and Cancer Cell Line Encyclopedia. Tumors were split into "APOBEC-high" and "APOBEC-low" based on APOBEC enrichment. Patients with APOBEC-high tumors have better overall survival compared to those with APOBEC-low tumors (38...
January 12, 2018: Oncotarget
https://www.readbyqxmd.com/read/29423038/suppression-of-fgfr3-and-myc-dependent-oncogenesis-by-tubacin-association-with-hdac6-dependent-and-independent-activities
#2
Sara Ota, Zi-Qiang Zhou, Peter J Hurlin
Fibroblast growth factor receptor 3 (FGFR3) is amplified, translocated or mutated in a number of different human cancer types, but most commonly in bladder cancers. We previously found that the accumulation of FGFR3 is dependent on histone deacetylase 6 (HDAC6). Here we show that HDAC6 loss or inhibition reduces FGFR3 accumulation in cells made tumorigenic by ectopic expression of a mutant activated version of FGFR3 together with the MYC oncoprotein and in a bladder cancer cell line whose tumorigenicity is dependent on expression of a translocated version of FGFR3...
January 9, 2018: Oncotarget
https://www.readbyqxmd.com/read/29396293/genomic-profile-of-urothelial-carcinoma-of-the-upper-tract-from-ureteroscopic-biopsy-feasibility-and-validation-using-matched-radical-nephroureterectomy-specimens
#3
Aditya Bagrodia, Francois Audenet, Eugene J Pietzak, Kwanghee Kim, Katie S Murray, Eugene K Cha, John P Sfakianos, Gopa Iyer, Nirmish Singla, Maria Arcila, Bernard H Bochner, Hikmat A Al-Ahmadie, David B Solit, Jonathan A Coleman
Urothelial carcinoma of the upper tract (UTUC) presents specific challenges regarding accurate staging and tumor sampling. We aimed to assess the feasibility of applying next-generation sequencing to biopsy specimens and gauged the concordance of their genetic profiles with matched radical nephroureterectomy (RNU) specimens. Of the 39 biopsy specimens collected, 36 (92%) had adequate material for sequencing using a hybridization-based exon capture assay (MSK-IMPACT). The most frequently altered genes across the patient cohort were consistent with the urothelial carcinoma-associated alterations identified in a cohort of 130 RNU specimens previously sequenced at our center, including mutations in the TERT promoter (64%), hotspot activating mutations in FGFR3 (64%), and frequent mutations in chromatin remodeling genes...
January 30, 2018: European Urology Focus
https://www.readbyqxmd.com/read/29380944/optimal-non-invasive-diagnosis-of-fetal-achondroplasia-combining-ultrasonography-and-circulating-cell-free-fetal-dna-analysis
#4
Alexandre J Vivanti, Jean-Marc Costa, Audrey Rosefort, Pascale Kleinfinger, Laurence Lohmann, Anne-Gael Cordier, Alexandra Benachi
OBJECTIVE: To assess the performance of non-invasive prenatal testing of achondroplasia using high-resolution melting (HRM) analysis. To propose an optimal diagnosis strategy combining ultrasound scan and cell-free fetal DNA (cffDNA) analysis. METHODS: Prospective multicenter study. CffDNA was extracted from maternal blood from women at risk for fetal achondroplasia (paternal achondroplasia, previous affected child or suspected rhizomelic shortening). The presence of one of the two main FGFR3 mutations was determined by HRM combined with confirmation by SNaPshot minisequencing...
January 30, 2018: Ultrasound in Obstetrics & Gynecology
https://www.readbyqxmd.com/read/29367430/molecular-markers-increase-precision-of-the-european-association-of-urology-non-muscle-invasive-bladder-cancer-progression-risk-groups
#5
Kim E Van Kessel, Kirstin A van der Keur, Lars Dyrskjøt, Ferran Algaba, Naeromy Yc Welvaart, Willemien Beukers, Ulrika Segersten, Bastian Keck, Tobias Maurer, Tatjana Simic, Marcus Horstmann, Marc-Oliver Grimm, Gregers G Hermann, Karin Mogensen, Arndt Hartmann, Niels Harving, Astrid C Petersen, Jørgen B Jensen, Kerstin Junker, Joost L Boormans, Francisco X Real, Nuria Malats, Per-Uno Malmström, Torben F Ørntoft, Ellen C Zwarthoff
PURPOSE: The European Association of Urology (EAU) guidelines for non-muscle invasive bladder cancer (NMIBC) recommend risk stratification based on clinicopathological parameters. Our aim was to investigate the added value of biomarkers to improve risk stratification of NMIBC. EXPERIMENTAL DESIGN: We prospectively included 1239 patients in follow-up for NMIBC in six European countries. Fresh frozen tumor samples were analyzed for GATA2, TBX2, TBX3 and ZIC4 methylation and FGFR3, TERT, PIK3CA and RAS mutation status...
January 24, 2018: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/29361062/rgbm-regularized-gradient-boosting-machines-for-identification-of-the-transcriptional-regulators-of-discrete-glioma-subtypes
#6
Raghvendra Mall, Luigi Cerulo, Luciano Garofano, Veronique Frattini, Khalid Kunji, Halima Bensmail, Thais S Sabedot, Houtan Noushmehr, Anna Lasorella, Antonio Iavarone, Michele Ceccarelli
We propose a generic framework for gene regulatory network (GRN) inference approached as a feature selection problem. GRNs obtained using Machine Learning techniques are often dense, whereas real GRNs are rather sparse. We use a Tikonov regularization inspired optimal L-curve criterion that utilizes the edge weight distribution for a given target gene to determine the optimal set of TFs associated with it. Our proposed framework allows to incorporate a mechanistic active biding network based on cis-regulatory motif analysis...
January 19, 2018: Nucleic Acids Research
https://www.readbyqxmd.com/read/29360984/regulation-of-ciliary-function-by-fibroblast-growth-factor-signaling-identifies-fgfr3-related-disorders-achondroplasia-and-thanatophoric-dysplasia-as-ciliopathies
#7
Michaela Kunova Bosakova, Miroslav Varecha, Marek Hampl, Ivan Duran, Alexandru Nita, Marcela Buchtova, Hana Dosedelova, Radek Machat, Yangli Xie, Zhenhong Ni, Jorge H Martin, Lin Chen, Gert Jansen, Deborah Krakow, Pavel Krejci
Cilia project from almost every cell integrating extracellular cues with signaling pathways. Constitutive activation of FGFR3 signaling produces the skeletal disorders achondroplasia (ACH) and thanatophoric dysplasia (TD), but many of the molecular mechanisms underlying these phenotypes remain unresolved. Here, we report in vivo evidence for significantly shortened primary cilia in ACH and TD cartilage growth plates. Using in vivo and in vitro methodologies, our data demonstrate that transient versus sustained activation of FGF signaling correlated with different cilia consequences...
January 17, 2018: Human Molecular Genetics
https://www.readbyqxmd.com/read/29358619/novel-therapeutic-strategy-for-cervical-cancer-harboring-fgfr3-tacc3-fusions
#8
Ryo Tamura, Kosuke Yoshihara, Tetsuya Saito, Ryosuke Ishimura, Juan Emmanuel Martínez-Ledesma, Hu Xin, Tatsuya Ishiguro, Yutaro Mori, Kaoru Yamawaki, Kazuaki Suda, Seiya Sato, Hiroaki Itamochi, Teiichi Motoyama, Yoichi Aoki, Shujiro Okuda, Cristine R Casingal, Hirofumi Nakaoka, Ituro Inoue, Roel G W Verhaak, Masaaki Komatsu, Takayuki Enomoto
We previously found that therapeutic targetable fusions are detected across various cancers. To identify therapeutic targetable fusion in uterine cervical cancer, for which no effective gene targeted therapy has yet been clinically applied, we analyzed RNA sequencing data from 306 cervical cancer samples. We detected 445 high confidence fusion transcripts and identified four samples that harbored FGFR3-TACC3 fusion as an attractive therapeutic target. The frequency of FGFR3-TACC3-fusion-positive cervical cancer is also 1...
January 23, 2018: Oncogenesis
https://www.readbyqxmd.com/read/29330265/fgfr3-tacc3-activates-mitochondrial-respiration-via-pin4-phosphorylation
#9
(no author information available yet)
PIN4 is a FGFR3-TACC3 substrate required for ROS-mediated induction of PGCIα and tumor growth.
January 12, 2018: Cancer Discovery
https://www.readbyqxmd.com/read/29323298/a-metabolic-function-of-fgfr3-tacc3-gene-fusions-in-cancer
#10
Véronique Frattini, Stefano M Pagnotta, Tala, Jerry J Fan, Marco V Russo, Sang Bae Lee, Luciano Garofano, Jing Zhang, Peiguo Shi, Genevieve Lewis, Heloise Sanson, Vanessa Frederick, Angelica M Castano, Luigi Cerulo, Delphine C M Rolland, Raghvendra Mall, Karima Mokhtari, Kojo S J Elenitoba-Johnson, Marc Sanson, Xi Huang, Michele Ceccarelli, Anna Lasorella, Antonio Iavarone
Chromosomal translocations that generate in-frame oncogenic gene fusions are notable examples of the success of targeted cancer therapies. We have previously described gene fusions of FGFR3-TACC3 (F3-T3) in 3% of human glioblastoma cases. Subsequent studies have reported similar frequencies of F3-T3 in many other cancers, indicating that F3-T3 is a commonly occuring fusion across all tumour types. F3-T3 fusions are potent oncogenes that confer sensitivity to FGFR inhibitors, but the downstream oncogenic signalling pathways remain unknown...
January 11, 2018: Nature
https://www.readbyqxmd.com/read/29323153/skeletal-characterization-of-the-fgfr3-mouse-model-of-achondroplasia-using-micro-ct-and-mri-volumetric-imaging
#11
Mohammed Salman Shazeeb, Megan K Cox, Anurag Gupta, Wen Tang, Kuldeep Singh, Cynthia T Pryce, Robert Fogle, Ying Mu, William D Weber, Dinesh S Bangari, Xiaoyou Ying, Yves Sabbagh
Achondroplasia, the most common form of dwarfism, affects more than a quarter million people worldwide and remains an unmet medical need. Achondroplasia is caused by mutations in the fibroblast growth factor receptor 3 (FGFR3) gene which results in over-activation of the receptor, interfering with normal skeletal development leading to disproportional short stature. Multiple mouse models have been generated to study achondroplasia. The characterization of these preclinical models has been primarily done with 2D measurements...
January 11, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29316748/-preliminary-study-of-exon-sequence-in-pneumoconiosis-and-pneumoconiosis-complicated-with-lung-cancer-using-high-throughput-sequencing-technology
#12
M F Jiang, L Li, Z Wang, C L Zhang, H Zhang
Objective: The detection and analysis of exon mutations of pneumoconiosis and pneumoco-niosis complicated with lung cancer provide reference evidence for screening, clinical diagnosis and treatment and prognosis in pneumoconiosis and pneumoconiosis complicated with lung cancer. Methods: The pathologi-cal tissue samples from 3 pneumoconiosis patients and 3 pneumoconiosis complicated with lung cancer pa-tients were collected. Genomic DNA was extracted and library was prepared. Exomes of the pathological tissue samples in pneumoconiosis patients and pneumoconiosis complicated with lung cancer patients were se-quenced using Ion Torrent PGM platform...
November 20, 2017: Chinese Journal of Industrial Hygiene and Occupational Diseases
https://www.readbyqxmd.com/read/29312631/proteomic-approach-toward-determining-the-molecular-background-of-pazopanib-resistance-in-synovial-sarcoma
#13
Zhiwei Qiao, Kumiko Shiozawa, Tadashi Kondo
Pazopanib, a multitarget tyrosine kinase (TK) inhibitor, has been approved for treatment of soft tissue sarcoma. Elucidation of the molecular background of pazopanib resistance should lead to improved clinical outcomes in sarcomas; accordingly, we investigated this in synovial sarcoma using a proteomic approach. Pazopanib sensitivity was examined in four synovial sarcoma cell lines: SYO-1, HS-SYII, 1273/99, and YaFuSS. The 1273/99 cell line showed significantly higher IC50 values than the others for pazopanib...
December 12, 2017: Oncotarget
https://www.readbyqxmd.com/read/29304256/dynamics-ultrastructure-and-gene-expression-of-human-in-vitro-organized-testis-cells-from-testicular-sperm-extraction-biopsies
#14
Kathrein von Kopylow, Wolfgang Schulze, Andrea Salzbrunn, Matthias Schaks, Elke Schäfer, Beate Roth, Stefan Schlatt, Andrej-Nikolai Spiess
STUDY QUESTION: Is it possible to induce in-vitro reorganization of primary human testis cells from testicular sperm extraction (TESE) biopsies, maintain their long-term cultivation in a 2D system and identify cellular compositions? SUMMARY ANSWER: In-vitro reorganization of primary human testis cells from TESE biopsies and their long-term cultivation on uncoated cell culture dishes is feasible and the cellular compositions can be uncovered through gene expression and microscopic analyses...
January 3, 2018: Molecular Human Reproduction
https://www.readbyqxmd.com/read/29299828/fibroblast-growth-factor-receptor-1-and-3-expression-is-associated-with-regulatory-pi3k-akt-kinase-activity-as-well-as-invasion-and-prognosis-in-human-laryngeal-cancer
#15
Katarzyna Starska, Ewa Forma, Iwona Lewy-Trenda, Olga Stasikowska-Kanicka, Michał Skóra, Magdalena Bryś
PURPOSE: Aberrant fibroblast growth factor receptor (FGFR) expression is thought to contribute to the development of many types of cancer. As yet, however, their impact on the course and prognosis of head and neck cancer remains to be determined. Here, we aimed to investigate the effects of expression of the FGFR family members FGFR1 and FGFR3, as well as their downstream PI3K/AKT signal-regulated kinases, on the aggressiveness and prognosis of laryngeal cancer. METHODS: In total 137 surgically removed squamous cell laryngeal cancer (SCLC) and 100 matched non-cancerous laryngeal mucosa (NCLM) samples were assessed for mRNA expression using quantitative real-time PCR...
January 3, 2018: Cellular Oncology (Dordrecht)
https://www.readbyqxmd.com/read/29277418/maternal-undernutrition-during-early-pregnancy-inhibits-postnatal-growth-of-the-tibia-in-the-female-offspring-of-rats-by-alteration-of-chondrogenesis
#16
Tomoko Kimura, Kodai Hino, Tadaaki Kono, Atsushi Takano, Norihisa Nitta, Noritoshi Ushio, Shinjiro Hino, Ryuta Takase, Motoi Kudo, Yataro Daigo, Wataru Morita, Mitsuyoshi Nakao, Masato Nakatsukasa, Toshihiro Tamagawa, Ashiq Mahmood Rafiq, Akihiro Matsumoto, Hiroki Otani, Jun Udagawa
Epidemiological research has suggested that birth weights are correlated with adult leg lengths. However, the relationship between prenatal undernutrition (UN) and postnatal leg growth remains controversial. We investigated the effects of UN during early pregnancy on postnatal hindlimb growth and determined whether early embryonic malnutrition affects the functions of postnatal chondrocytes in rats. Undernourished Wistar dams were fed 40% of the daily intake of rats in the control groups from gestational days 5...
December 22, 2017: General and Comparative Endocrinology
https://www.readbyqxmd.com/read/29242604/ribosomal-protein-s15a-promotes-tumor-angiogenesis-via-enhancing-wnt-%C3%AE-catenin-induced-fgf18-expression-in-hepatocellular-carcinoma
#17
Pengyi Guo, Yi Wang, Chunxiu Dai, Chonglin Tao, Fang Wu, Xiaozai Xie, Haitao Yu, Qiandong Zhu, Junjian Li, Longyun Ye, Fuxiang Yu, Yunfeng Shan, Zhengping Yu, Renumathy Dhanasekaran, Rongyuan Zheng, Gang Chen
Ribosomal protein s15a (RPS15A) plays a promotive role in the mRNA/ribosome interactions during early translation. Our previous study has found that inhibiting RPS15A expression can decrease proliferation and induce cell cycle arrest in hepatocellular carcinoma (HCC) cell lines. However, the mechanism underlying the involvement of RPS15A in HCC pathogenesis and the clinical significance of RPS15A expression remain unclear. In this study, an evaluation of RPS15A expression in 110 surgically resected HCCs and matched tumor-adjacent normal tissues revealed an overexpression of RPS15A in HCC, which was correlated with worse survival...
December 15, 2017: Oncogene
https://www.readbyqxmd.com/read/29242050/mutant-fgfr3-associated-with-saddan-disease-causes-cytoskeleton-disorganization-through-plc%C3%AE-1-src-mediated-paxillin-hyperphosphorylation
#18
R Montone, M G Romanelli, A Baruzzi, F Ferrarini, E Liboi, P M-J Lievens
K650M/E substitutions in the Fibroblast growth factor receptor 3 (FGFR3) are associated with Severe Achondroplasia with Developmental Delay and Acanthosis Nigricans (SADDAN) and Thanatophoric Dysplasia type II (TDII), respectively. Both SADDAN and TDII present with affected endochondral ossification marked by impaired chondrocyte functions and growth plate disorganization. In vitro, K650M/E substitutions confer FGFR3 constitutive kinase activity leading to impaired biosynthesis and accumulation of immature receptors in endoplasmic reticulum (ER)/Golgi...
December 11, 2017: International Journal of Biochemistry & Cell Biology
https://www.readbyqxmd.com/read/29226855/knockdown-of-long-noncoding-rna-fgfr3-as1-induces-cell-proliferation-inhibition-apoptosis-and-motility-reduction-in-bladder-cancer
#19
Xinhui Liao, Jieqing Chen, Yuchen Liu, Anbang He, Jianting Wu, Jianli Cheng, Xintao Zhang, Zhaojie Lv, Feng Wang, Hongbing Mei
OBJECTIVES: To study the expression pattern of long non-coding RNA FGFR3 antisense transcript 1(FGFR3-AS1) and the cell proliferation inhibition, apoptosis, and motility changes induced by silencing FGFR3-AS1 in bladder cancer. METHODS: The differential expression levels of FGFR3-AS1 and FGFR3 in tumor tissues and paired normal tissues were determined using Real-Time qPCR in a total of 36 patients diagnosed with bladder cancer (urothelial carcinoma). Pearson's coefficient correlation was used for expression correlation assay...
November 27, 2017: Cancer Biomarkers: Section A of Disease Markers
https://www.readbyqxmd.com/read/29193225/biological-significance-of-tert-promoter-mutation-in-papillary-urothelial-neoplasm-of-low-malignant-potential
#20
Chung-Chieh Wang, Chao-Yuan Huang, Yu-Lin Jhuang, Chih-Chi Chen, Yung-Ming Jeng
AIMS: Mutations in FGFR3 and the promoter region of the telomerase reverse transcriptase (TERT) gene have been found frequently in urothelial carcinoma of the urinary bladder. However, related data for papillary urothelial neoplasm of low malignant potential (PUNLMP) are limited. In this study, we investigated the mutation status of the TERT promoter, FGFR3 and HRAS in low-grade papillary urothelial neoplasms and evaluated their prognostic significance. METHODS AND RESULTS: The cases included in this study comprised 21 inverted papillomas, 30 PUNLMPs and 34 low-grade non-invasive papillary urothelial carcinomas (NIPUCs)...
November 28, 2017: Histopathology
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