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Ewing sarcoma chromosome translocation

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https://www.readbyqxmd.com/read/29626752/efficacy-of-onc201-in-desmoplastic-small-round-cell-tumor
#1
Andrea A Hayes-Jordan, Xiao Ma, Brian A Menegaz, Salah-Eddine Lamhamedi-Cherradi, Charles V Kingsley, Jalen A Benson, Pamela E Camacho, Joseph A Ludwig, Cynthia R Lockworth, Gloria E Garcia, Suzanne L Craig
Desmoplastic Small Round Cell Tumor (DSRCT) is a rare sarcoma tumor of adolescence and young adulthood, which harbors a recurrent chromosomal translocation between the Ewing's sarcoma gene (EWSR1) and the Wilms' tumor suppressor gene (WT1). Patients usually develop multiple abdominal tumors with liver and lymph node metastasis developing later. Survival is poor using a multimodal therapy that includes chemotherapy, radiation and surgical resection, new therapies are needed for better management of DSRCT. Triggering cell apoptosis is the scientific rationale of many cancer therapies...
April 4, 2018: Neoplasia: An International Journal for Oncology Research
https://www.readbyqxmd.com/read/29581854/ire1%C3%AE-xbp1-inhibitors-exerted-anti-tumor-activities-in-ewing-s-sarcoma
#2
Yu Tanabe, Yoshiyuki Suehara, Shinji Kohsaka, Takuo Hayashi, Keisuke Akaike, Kenta Mukaihara, Taisei Kurihara, Youngji Kim, Taketo Okubo, Midori Ishii, Saiko Kazuno, Kazuo Kaneko, Tsuyoshi Saito
Ewing's sarcoma (ES) is the second-most frequent pediatric bone tumor. Chromosomal translocation t(11;22)(q24:q12) results in the formation of EWS/FLI1 gene fusion, which is detected in approximately 90% of tumors of the Ewing family. Several transcriptome studies have provided lists of genes associated with EWS/FLI1 expression. However, the protein expression profiles associated with EWS/FLI1 have yet to be elucidated. In this study, to identify the regulated proteins associated with EWS/FLI1 and therapeutic targets in ES, we conducted proteomic studies using EWS/FLI1 knockdown in four Ewing's sarcoma cell lines and human mesenchymal stem cells (hMSCs) expressing EWS/FLI1...
March 6, 2018: Oncotarget
https://www.readbyqxmd.com/read/29580035/fluorescence-in-situ-hybridization-fish-for-differential-diagnosis-of-soft-tissue-sarcomas
#3
Amna Asif, Sajid Mushtaq, Usman Hassan, Noreen Akhtar, Mudassar Hussain, Muhammad Azam, Romena Qazi
Introduction:Soft tissue sarcomas are rare tumors comprising 1 percent of solid malignancies. The latest edition of WHO soft tissue pathology lists 94 benign and malignant soft tissue tumors. Many of these show a large degree of morphological overlap. Immunohistochemistry has been shown to be reliable in many cases for differential diagnosis of lesions, although cytogenetic tests are considered the gold standard for many entities.Fluorescence in-situ hybridization (FISH) is a cytogenetic technique that uses fluorescent probes that bind to only those parts of the chromosome which have a high degree of sequence complementarity...
March 27, 2018: Asian Pacific Journal of Cancer Prevention: APJCP
https://www.readbyqxmd.com/read/29513652/ews-fli1-increases-transcription-to-cause-r-loops-and-block-brca1-repair-in-ewing-sarcoma
#4
Aparna Gorthi, July Carolina Romero, Eva Loranc, Lin Cao, Liesl A Lawrence, Elicia Goodale, Amanda Balboni Iniguez, Xavier Bernard, V Pragathi Masamsetti, Sydney Roston, Elizabeth R Lawlor, Jeffrey A Toretsky, Kimberly Stegmaier, Stephen L Lessnick, Yidong Chen, Alexander J R Bishop
Ewing sarcoma is an aggressive paediatric cancer of the bone and soft tissue. It results from a chromosomal translocation, predominantly t(11;22)(q24:q12), that fuses the N-terminal transactivation domain of the constitutively expressed EWSR1 protein with the C-terminal DNA binding domain of the rarely expressed FLI1 protein. Ewing sarcoma is highly sensitive to genotoxic agents such as etoposide, but the underlying molecular basis of this sensitivity is unclear. Here we show that Ewing sarcoma cells display alterations in regulation of damage-induced transcription, accumulation of R-loops and increased replication stress...
March 15, 2018: Nature
https://www.readbyqxmd.com/read/29386915/detection-of-circulating-tumor-cells-in-liquid-biopsy-from-ewing-sarcoma-patients
#5
Stefania Benini, Gabriella Gamberi, Stefania Cocchi, Jessica Garbetta, Laurent Alberti, Alberto Righi, Marco Gambarotti, Piero Picci, Stefano Ferrari
Background: Circulating tumor cells (CTCs) analysis is a promising new diagnostic field to estimate risk and monitor treatment efficacy, metastatic relapse, and progression in cancer patients. The study aim was to isolate and characterize CTCs in blood samples of Ewing sarcoma (ES) patients exploiting two main characteristics: CD99 expression and presence of chromosomal translocations. Materials and methods: The method isolated CTCs from peripheral blood (PB) of ES patients...
2018: Cancer Management and Research
https://www.readbyqxmd.com/read/29321818/ews-fli-1-creates-a-cell-surface-microenvironment-conducive-to-igf-signaling-by-inducing-pappalysin-1
#6
Panneerselvam Jayabal, Peter J Houghton, Yuzuru Shiio
Ewing sarcoma is an aggressive cancer of bone and soft tissue in children with poor prognosis. It is characterized by the chromosomal translocation between EWS and an Ets family transcription factor, most commonly FLI-1. EWS-FLI-1 fusion accounts for 85% of Ewing sarcoma cases. EWS-FLI-1 regulates the expression of a number of genes important for sarcomagenesis, can transform NIH3T3 and C3H10T1/2 cells, and is necessary for proliferation and tumorigenicity of Ewing sarcoma cells, suggesting that EWS-FLI-1 is the causative oncoprotein...
November 2017: Genes & Cancer
https://www.readbyqxmd.com/read/29247978/advances-in-chromosomal-translocations-and-fusion-genes-in-sarcomas-and-potential-therapeutic-applications
#7
REVIEW
Xin Xiao, Cassandra C Garbutt, Francis Hornicek, Zheng Guo, Zhenfeng Duan
Chromosomal translocations and fusion genes are very common in human cancer especially in subtypes of sarcomas, such as rhabdomyosarcoma, Ewing's sarcoma, synovial sarcoma and liposarcoma. The discovery of novel chromosomal translocations and fusion genes in different tumors are due to the advancement of next-generation sequencing (NGS) technologies such as whole genome sequencing. Recently, many novel chromosomal translocations and gene fusions have been identified in different types of sarcoma through NGS approaches...
February 2018: Cancer Treatment Reviews
https://www.readbyqxmd.com/read/29091716/identification-of-two-types-of-ggaa-microsatellites-and-their-roles-in-ews-fli-binding-and-gene-regulation-in-ewing-sarcoma
#8
Kirsten M Johnson, Cenny Taslim, Ranajeet S Saund, Stephen L Lessnick
Ewing sarcoma is a bone malignancy of children and young adults, frequently harboring the EWS/FLI chromosomal translocation. The resulting fusion protein is an aberrant transcription factor that uses highly repetitive GGAA-containing elements (microsatellites) to activate and repress thousands of target genes mediating oncogenesis. However, the mechanisms of EWS/FLI interaction with microsatellites and regulation of target gene expression is not clearly understood. Here, we profile genome-wide protein binding and gene expression...
2017: PloS One
https://www.readbyqxmd.com/read/29045981/renal-ewing-s-sarcoma-primitive-neuroectodermal-tumor-a-case-report-and-literature-review
#9
C Liu, L G Cui, H L Wang
Ewing's sarcoma/primitive neuroectodermal tumor (EWS/PNET) in the kidney is a rare but high-grade malignant tumor that affects predominantly elder children and adolescents. Patients mostly present with nonspecific symptoms such as abdominal pain and gross hematuria. Since EWS/PNET has a rapid clinical progression with early metastasis and death, it is essential to make an accurate and early diagnosis. Once diagnosed, multimodality treatment, including radical surgery combined with adjuvant chemotherapy, and radiotherapy if necessary, is recommended...
October 18, 2017: Beijing da Xue Xue Bao. Yi Xue Ban, Journal of Peking University. Health Sciences
https://www.readbyqxmd.com/read/28985030/a-double-edged-sword-the-world-according-to-capicua-in-cancer
#10
REVIEW
Miwa Tanaka, Toyoki Yoshimoto, Takuro Nakamura
CIC/Capicua is an HMG-box transcription factor that is well conserved during evolution. CIC recognizes the T(G/C)AATG(A/G)A sequence and represses its target genes, such as PEA3 family genes. The receptor tyrosine kinase/RAS/MAPK signals downregulate CIC and relieves CIC's target genes from the transrepressional activity; CIC thus acts as an important downstream molecule of the pathway and as a tumor suppressor. CIC loss-of-function mutations are frequently observed in several human neoplasms such as oligodendroglioma, and lung and gastric carcinoma...
December 2017: Cancer Science
https://www.readbyqxmd.com/read/28974650/inhibition-of-the-oncogenic-fusion-protein-ews-fli1-causes-g-2-m-cell-cycle-arrest-and-enhanced-vincristine-sensitivity-in-ewing-s-sarcoma
#11
Stefan K Zöllner, Saravana P Selvanathan, Garrett T Graham, Ryan M T Commins, Sung Hyeok Hong, Eric Moseley, Sydney Parks, Jessica N Haladyna, Hayriye V Erkizan, Uta Dirksen, Michael D Hogarty, Aykut Üren, Jeffrey A Toretsky
Ewing's sarcoma (ES) is a rare and highly malignant cancer that grows in the bones or surrounding tissues mostly affecting adolescents and young adults. A chimeric fusion between the RNA binding protein EWS and the ETS family transcription factor FLI1 (EWS-FLI1), which is generated from a chromosomal translocation, is implicated in driving most ES cases by modulation of transcription and alternative splicing. The small-molecule YK-4-279 inhibits EWS-FLI1 function and induces apoptosis in ES cells. We aimed to identify both the underlying mechanism of the drug and potential combination therapies that might enhance its antitumor activity...
October 3, 2017: Science Signaling
https://www.readbyqxmd.com/read/28902354/ews-fli1-positively-regulates-autophagy-by-increasing-atg4b-expression-in-ewing-sarcoma-cells
#12
Qunshan Lu, Yuankai Zhang, Liang Ma, Deqiang Li, Ming Li, Jianmin Li, Peilai Liu
Ewing sarcoma (ES) is the most common malignant bone tumor in children and young adults. It is characterized by chromosomal translocations fusing the EWS gene with an ETS oncogene, most frequently FLI1. In the present study, the authors aimed to investigate the function of EWS-FLI1 in autophagy in ES cells, and identified that EWS-FLI1 positively regulates autophagy in ES cells. ATG4B expression was observed markedly upregulated by EWS-FLI1 overexpression, and silencing of ATG4B dramatically inhibits autophagy in ES cells...
October 2017: International Journal of Molecular Medicine
https://www.readbyqxmd.com/read/28797503/ewing-sarcoma-an-update-on-molecular-pathology-with-therapeutic-implications
#13
REVIEW
Enrique de Alava
Ewing sarcoma is a developmental tumor characterized by balanced chromosomal translocations and formation of new fusion genes. Despite the large amount of knowledge regarding the molecular aspects obtained in the last few years, many questions still remain. This article focuses on research on the molecular pathology and possible developments in targeted therapies in this malignancy and discusses some related bottlenecks, as well as the possible role of pathologists, the availability of samples, the lack of appropriate animal models, and the resources needed to carry out preclinical and clinical research...
September 2017: Surgical Pathology Clinics
https://www.readbyqxmd.com/read/28745431/trabectedin-is-a-promising-antitumor-agent-potentially-inducing-melanocytic-differentiation-for-clear-cell-sarcoma
#14
Takaaki Nakai, Yoshinori Imura, Hironari Tamiya, Shutaro Yamada, Sho Nakai, Naohiro Yasuda, Keiko Kaneko, Hidetatsu Outani, Satoshi Takenaka, Kenichiro Hamada, Akira Myoui, Nobuhito Araki, Takafumi Ueda, Kazuyuki Itoh, Hideki Yoshikawa, Norifumi Naka
Clear cell sarcoma is an aggressive soft tissue sarcoma and highly resistant to conventional chemotherapy and radiation therapy. This devastating disease is defined by EWSR1-ATF1 fusion gene resulting from chromosomal translocation t(12;22)(q13;q12) and characterized by melanocytic differentiation. A marine-derived antineoplastic agent, trabectedin, inhibits the growth of myxoid liposarcoma and Ewing sarcoma by causing adipogenic differentiation and neural differentiation, respectively. In this study, we examined the antitumor effects and mechanism of action of trabectedin on human clear cell sarcoma cell lines...
September 2017: Cancer Medicine
https://www.readbyqxmd.com/read/28494941/efficient-recreation-of-t-11-22-ewsr1-fli1-in-human-stem-cells-using-crispr-cas9
#15
Raul Torres-Ruiz, Marta Martinez-Lage, Maria C Martin, Aida Garcia, Clara Bueno, Julio Castaño, Juan C Ramirez, Pablo Menendez, Juan C Cigudosa, Sandra Rodriguez-Perales
Efficient methodologies for recreating cancer-associated chromosome translocations are in high demand as tools for investigating how such events initiate cancer. The CRISPR/Cas9 system has been used to reconstruct the genetics of these complex rearrangements at native loci while maintaining the architecture and regulatory elements. However, the CRISPR system remains inefficient in human stem cells. Here, we compared three strategies aimed at enhancing the efficiency of the CRISPR-mediated t(11;22) translocation in human stem cells, including mesenchymal and induced pluripotent stem cells: (1) using end-joining DNA processing factors involved in repair mechanisms, or (2) ssODNs to guide the ligation of the double-strand break ends generated by CRISPR/Cas9; and (3) all-in-one plasmid or ribonucleoprotein complex-based approaches...
May 9, 2017: Stem Cell Reports
https://www.readbyqxmd.com/read/28319320/the-endochondral-bone-protein-chm1-sustains-an-undifferentiated-invasive-phenotype-promoting-lung-metastasis-in-ewing-sarcoma
#16
Kristina von Heyking, Julia Calzada-Wack, Stefanie Göllner, Frauke Neff, Oxana Schmidt, Tim Hensel, David Schirmer, Annette Fasan, Irene Esposito, Carsten Müller-Tidow, Poul H Sorensen, Stefan Burdach, Günther H S Richter
Ewing sarcomas (ES) are highly malignant, osteolytic bone or soft tissue tumors, which are characterized by EWS-ETS translocations and early metastasis to lung and bone. In this study, we investigated the role of the BRICHOS chaperone domain-containing endochondral bone protein chondromodulin I (CHM1) in ES pathogenesis. CHM1 is significantly overexpressed in ES, and chromosome immunoprecipitation (ChIP) data demonstrate CHM1 to be directly bound by an EWS-ETS translocation, EWS-FLI1. Using RNA interference, we observed that CHM1 promoted chondrogenic differentiation capacity of ES cells but decreased the expression of osteolytic genes such as HIF1A, IL6, JAG1, and VEGF...
September 2017: Molecular Oncology
https://www.readbyqxmd.com/read/28255420/complete-resection-of-a-primitive-neuroectodermal-tumour-arising-in-the-bladder-of-a-31-year-old-female-after-neoadjuvant-chemotherapy
#17
Cameron J Lam, Bobby Shayegan
Primitive neuroectodermal tumours (PNET) that arise in the urinary bladder are an extremely rare occurrence. Very few cases have been reported so far in the literature1-13 and we report another case here in a 31-year-old-female. The patient presented with polyuria, gross hematuria, followed by development of anuria, and was discovered to have a 9.4 cm mass arising in the posterolateral aspect of the bladder. Histologically, the tumour showed small, round, blue cells. Further analysis using break-apart fluorescent in situ hybridization (FISH) revealed non-random chromosomal translocations of the ews gene suggestive of Ewing sarcoma (ES)/PNET...
July 2016: Canadian Urological Association Journal, Journal de L'Association des Urologues du Canada
https://www.readbyqxmd.com/read/28203170/primary-ewing-s-sarcoma-of-the-sinonasal-tract-a-case-report
#18
Tomoharu Suzuki, Ryuji Yasumatsu, Torahiko Nakashima, Shuji Arita, Hidetaka Yamamoto, Takashi Nakagawa
A 23-year-old male presented with a 3-month history of left purulent rhinorrhea, progressive nasal obstruction, and intermittent epistaxis. A fiberoptic examination revealed a large vascular polypoid mass completely filling the left nasal cavity. CT and MRI scans showed a large hypervascular mass involving the left nasal airway, maxillary antrum, and the anterior ethmoid cells. There was no bony erosion or contiguous spread, and the remaining sinuses, orbit, and cranial fossa were uninvolved. The patient underwent complete removal of the mass via an external lateral rhinotomy approach...
January 2017: Case Reports in Oncology
https://www.readbyqxmd.com/read/28188619/generation-of-conditional-oncogenic-chromosomal-translocations-using-crispr-cas9-genomic-editing-and-homology-directed-repair
#19
Lee Spraggon, Luciano G Martelotto, Julija Hmeljak, Tyler D Hitchman, Jiang Wang, Lu Wang, Emily K Slotkin, Pang-Dian Fan, Jorge S Reis-Filho, Marc Ladanyi
Chromosomal rearrangements encoding oncogenic fusion proteins are found in a wide variety of malignancies. The use of programmable nucleases to generate specific double-strand breaks in endogenous loci, followed by non-homologous end joining DNA repair, has allowed several of these translocations to be generated as constitutively expressed fusion genes within a cell population. Here, we describe a novel approach that combines CRISPR-Cas9 technology with homology-directed repair to engineer, capture, and modulate the expression of chromosomal translocation products in a human cell line...
May 2017: Journal of Pathology
https://www.readbyqxmd.com/read/28160567/ews-fli1-confers-exquisite-sensitivity-to-nampt-inhibition-in-ewing-sarcoma-cells
#20
Cornelia N Mutz, Raphaela Schwentner, Dave N T Aryee, Eric D J Bouchard, Edgard M Mejia, Grant M Hatch, Maximilian O Kauer, Anna M Katschnig, Jozef Ban, Antje Garten, Javier Alonso, Versha Banerji, Heinrich Kovar
Ewing sarcoma (EwS) is the second most common bone cancer in children and adolescents with a high metastatic potential. EwS development is driven by a specific chromosomal translocation resulting in the generation of a chimeric EWS-ETS transcription factor, most frequently EWS-FLI1.Nicotinamide adenine dinucleotide (NAD) is a key metabolite of energy metabolism involved in cellular redox reactions, DNA repair, and in the maintenance of genomic stability. This study describes targeting nicotinamide phosphoribosyltransferase (NAMPT), the rate-limiting enzyme of NAD synthesis, by FK866 in EwS cells...
April 11, 2017: Oncotarget
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