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Matthias Holdhoff, Gregory J Cairncross, Thomas M Kollmeyer, Ming Zhang, Peixin Zhang, Minesh P Mehta, Maria Werner-Wasik, Luis Souhami, Jean-Paul Bahary, Young Kwok, Alan C Hartford, Arnab Chakravarti, Srinivasan Yegnasubramanian, Bert Vogelstein, Nickolas Papadopoulos, Kenneth Kinzler, Robert B Jenkins, Chetan Bettegowda
BACKGROUND: The NRG Oncology RTOG 9402 trial showed significant survival benefit in patients with 1p/19q co-deleted anaplastic oligodendrogliomas (AO) who received both radiation (RT) and chemotherapy (PCV regimen) versus RT alone. Substantial separation of the survival curves was only seen after 7.3 years. We aimed to determine whether there are specific genetic alterations that distinguish co-deleted AO patients who benefit from the addition of PCV from those who do not. METHODS: We performed whole exome sequencing on matched tumor and normal DNA from all available short-term (STS) and long-term survivors (LTS) who received RT+PCV...
March 31, 2017: Oncotarget
Kai Guo, Jie Yao, Qiang Yu, Zijian Li, Hu Huang, Jianguo Cheng, Zhigang Wang, Yunfeng Zhu
The plasmacytoma variant translocation 1 gene (PVT1) is a large non-coding locus at adjacent of c-Myc, and long non-coding RNA PVT1 is now recognized as a cancerous gene co-amplified with c-Myc in various cancers. But the expression and functional role of PVT1 in colorectal cancer are still unelucidated. In addition, all the reported long non-coding RNAs so far are discovered in either cells or tissues, but no research about long non-coding RNAs detection in extracellular vesicles has been reported yet. In the present study, we firstly investigated the expression of PVT1 in colorectal cancer specimens and its correlation with the expression of c-Myc and other related genes by real-time polymerase chain reaction...
April 2017: Tumour Biology: the Journal of the International Society for Oncodevelopmental Biology and Medicine
Koki Aihara, Akitake Mukasa, Genta Nagae, Masashi Nomura, Shogo Yamamoto, Hiroki Ueda, Kenji Tatsuno, Junji Shibahara, Miwako Takahashi, Toshimitsu Momose, Shota Tanaka, Shunsaku Takayanagi, Shunsuke Yanagisawa, Takahide Nejo, Satoshi Takahashi, Mayu Omata, Ryohei Otani, Kuniaki Saito, Yoshitaka Narita, Motoo Nagane, Ryo Nishikawa, Keisuke Ueki, Hiroyuki Aburatani, Nobuhito Saito
Among diffuse gliomas, oligodendrogliomas show relatively better prognosis, respond well to radiotherapy and chemotherapy, and seldom progress to very aggressive tumors. To elucidate the genetic and epigenetic background for such behavior and tumor evolution during tumor relapse, we comparatively analyzed 12 pairs of primary and recurrent oligodendrogliomas with 1p/19q-codeletion. Initial treatment for these patients was mostly chemotherapy alone. Temozolomide was used for 3, and procarbazine, nimustine and vincristine (PAV chemotherapy) were used for 7 patients...
March 7, 2017: Acta Neuropathologica Communications
William Poole, Kalle Leinonen, Ilya Shmulevich, Theo A Knijnenburg, Brady Bernard
Cancer researchers have long recognized that somatic mutations are not uniformly distributed within genes. However, most approaches for identifying cancer mutations focus on either the entire-gene or single amino-acid level. We have bridged these two methodologies with a multiscale mutation clustering algorithm that identifies variable length mutation clusters in cancer genes. We ran our algorithm on 539 genes using the combined mutation data in 23 cancer types from The Cancer Genome Atlas (TCGA) and identified 1295 mutation clusters...
February 2017: PLoS Computational Biology
Junyao Duan, Xu Bao, Xin Ma, Yu Zhang, Dong Ni, Hanfeng Wang, Fan Zhang, Qingshan Du, Yang Fan, Jianwen Chen, Shengpan Wu, Xintao Li, Yu Gao, Xu Zhang
OBJECTIVE: The far upstream element (FUSE)-binding protein 1 (FUBP1) is a transactivator of human c-myc proto-oncogene transcription, with important roles in carcinogenesis. However, the expression pattern and potential biological function of FUBP1 in clear cell renal cell carcinoma (ccRCC) is yet to be established. METHODS: FUBP1 expression was detected in ccRCC tissues and cell lines by real-time RT-PCR, Western blot analysis, and immunohistochemistry. The correlations of FUBP1 mRNA expression levels with clinicopathological factors were evaluated...
2017: PloS One
Stefanie Hauck, Kerstin Hiesinger, Sabrina Khageh Hosseini, Janosch Achenbach, Ricardo M Biondi, Ewgenij Proschak, Martin Zörnig, Dalibor Odadzic
The transcriptional regulator FUSE binding protein 1 (FUBP1) is aberrantly upregulated in various malignancies, fulfilling its oncogenic role by the deregulation of critical genes involved in cell cycle control and apoptosis regulation. Thus, the pharmaceutical inhibition of this protein would represent an encouraging novel targeted chemotherapy. Here, we demonstrate the identification and initial optimization of a pyrazolo[1,5a]pyrimidine-based FUBP1 inhibitor derived from medium throughput screening, which interferes with the binding of FUBP1 to its single stranded target DNA FUSE...
September 14, 2016: Bioorganic & Medicinal Chemistry
Jana Kralovicova, Igor Vorechovsky
The auxiliary factor of U2 small nuclear ribonucleoprotein (U2AF) facilitates branch point (BP) recognition and formation of lariat introns. The gene for the 35-kD subunit of U2AF gives rise to two protein isoforms (termed U2AF35a and U2AF35b) that are encoded by alternatively spliced exons 3 and Ab, respectively. The splicing recognition sequences of exon 3 are less favorable than exon Ab, yet U2AF35a expression is higher than U2AF35b across tissues. We show that U2AF35b repression is facilitated by weak, closely spaced BPs next to a long polypyrimidine tract of exon Ab...
January 9, 2017: Nucleic Acids Research
Jiaqiang Wang, Xin Li, Leyun Wang, Jingyu Li, Yanhua Zhao, Gerelchimeg Bou, Yufei Li, Guanyi Jiao, Xinghui Shen, Renyue Wei, Shichao Liu, Bingteng Xie, Lei Lei, Wei Li, Qi Zhou, Zhonghua Liu
Endogenous retroviruses (ERVs) are transcriptionally active in cleavage stage embryos, yet their functions are unknown. ERV sequences are present in the majority of long intergenic noncoding RNAs (lincRNAs) in mouse and humans, playing key roles in many cellular processes and diseases. Here, we identify LincGET as a nuclear lincRNA that is GLN-, MERVL-, and ERVK-associated and essential for mouse embryonic development beyond the two-cell stage. LincGET is expressed in late two- to four-cell mouse embryos. Its depletion leads to developmental arrest at the late G2 phase of the two-cell stage and to MAPK signaling pathway inhibition...
October 2016: EMBO Reports
Pavel Klener, Eva Fronkova, Adela Berkova, Radek Jaksa, Halka Lhotska, Kristina Forsterova, Jan Soukup, Vojtech Kulvait, Jarmila Vargova, Karel Fiser, Dana Prukova, Mahmudul Alam, Bokang Calvin Lenyeletse Maswabi, Kyra Michalova, Zuzana Zemanova, Tereza Jancuskova, Sona Pekova, Marek Trneny
Richter syndrome represents the transformation of the chronic lymphocytic leukemia (CLL) into an aggressive lymphoma, most frequently the diffuse large B-cell lymphoma (DLBCL). In this report we describe a patient with CLL, who developed a clonally-related pleomorphic highly-aggressive mantle cell lymphoma (MCL) after five cycles of a fludarabine-based second-line therapy for the first relapse of CLL. Molecular cytogenetic methods together with whole-exome sequencing revealed numerous gene alterations restricted to the MCL clone (apart from the canonical t(11;14)(q13;q32) translocation) including gain of one copy of ATM gene or emergence of TP53, CREBBP, NUP214, FUBP1 and SF3B1 gene mutations...
November 15, 2016: International Journal of Cancer. Journal International du Cancer
Dae Gyu Kim, Jin Young Lee, Ji-Hyun Lee, Ha Yeon Cho, Beom Sik Kang, Song-Yee Jang, Myung Hee Kim, Min Guo, Jung Min Han, Seong-Jin Kim, Sunghoon Kim
AIMP2/p38 is a multifunctional tumor suppressor that normally resides in the cytosol as a scaffold protein of the multi-tRNA synthetase complex (MSC). One of the tumor-suppressive functions of AIMP2 is to facilitate ubiquitin-mediated degradation of FUSE-binding protein (FBP, FUBP1), a transcriptional activator of c-Myc. However, the mechanism by which AIMP2 functions within this pathway and its significance in tumorigenesis are uncertain. Here, we report that Smurf2 is responsible for AIMP2-mediated ubiquitination of FBP, and a mutation in AIMP2 that inhibited its nuclear interaction with Smurf2 enhanced cellular transformation and tumorigenesis in vivo Treatment of HeLa cells with TGFβ resulted in the phosphorylation of AIMP2 on S156, a residue that is exposed on the embedded GST domain of AIMP2...
June 1, 2016: Cancer Research
L Venturutti, R I Cordo Russo, M A Rivas, M F Mercogliano, F Izzo, R H Oakley, M G Pereyra, M De Martino, C J Proietti, P Yankilevich, J C Roa, P Guzmán, E Cortese, D H Allemand, T H Huang, E H Charreau, J A Cidlowski, R Schillaci, P V Elizalde
ErbB-2 amplification/overexpression accounts for an aggressive breast cancer (BC) subtype (ErbB-2-positive). Enhanced ErbB-2 expression was also found in gastric cancer (GC) and has been correlated with poor clinical outcome. The ErbB-2-targeted therapies trastuzumab (TZ), a monoclonal antibody, and lapatinib, a tyrosine kinase inhibitor, have proved highly beneficial. However, resistance to such therapies remains a major clinical challenge. We here revealed a novel mechanism underlying the antiproliferative effects of both agents in ErbB-2-positive BC and GC...
December 1, 2016: Oncogene
Yang Hong, Yu Shi, Chao Shang, Yixue Xue, Yunhui Liu
INTRODUCTION: The aim of this study was to determine the influence of the far upstream element binding protein 1 gene (FUBP1) on chemotherapy sensitivity in human U251 glioblastoma cells. MATERIAL AND METHODS: Real-time polymerase chain reaction (PCR) was used to determine the expression of the FUBP1 gene in 43 cases of human brain gliomas. Western blot analysis was used to determine the inhibitory effect of RNA interference on FUBP1 gene expression. Methyl thiazolyl tetrazolium assay (MTT) and flow cytometry methods were used to determine the growth inhibitory rate and apoptosis rate of the U251 cells with FUBP1 silencing...
February 1, 2016: Archives of Medical Science: AMS
Wang Zheng, Fan Shen, Ruikun Hu, Birbickram Roy, JungWoo Yang, Qian Wang, Fan Zhang, Jennifer C King, Consolato Sergi, Song-Mei Liu, Emmanuelle Cordat, Jingfeng Tang, Ying Cao, Declan Ali, Xing-Zhen Chen
Autosomal dominant polycystic kidney disease pathogenesis can be recapitulated in animal models by gene mutations in or dosage alterations of polycystic kidney disease 1 (PKD1) or PKD2, demonstrating that too much and too little PKD1/PKD2 are both pathogenic. Gene dosage manipulation has become an appealing approach by which to compensate for loss or gain of gene function, but the mechanisms controlling PKD2 expression remain incompletely characterized. In this study, using cultured mammalian cells and dual-luciferase assays, we found that the 3' untranslated region (3'UTR) of PKD2 mRNA inhibits luciferase protein expression...
September 2016: Journal of the American Society of Nephrology: JASN
Weixin Zhou, Yang Jo Chung, Edgardo R Parrilla Castellar, Ying Zheng, Hye-Jung Chung, Russell Bandle, Juhong Liu, Lino Tessarollo, Eric Batchelor, Peter D Aplan, David Levens
The transcription factor far upstream element binding protein (FBP) binds and activates the MYC promoter when far upstream element is via TFIIH helicase activity early in the transcription cycle. The fundamental biology and pathology of FBP are complex. In some tumors FBP seems pro-oncogenic, whereas in others it is a tumor suppressor. We generated an FBP knockout (Fubp1(-/-)) mouse to study FBP deficiency. FBP is embryo lethal from embryonic day 10.5 to birth. A spectrum of pathology is associated with FBP loss; besides cerebral hyperplasia and pulmonary hypoplasia, pale livers, hypoplastic spleen, thymus, and bone marrow, cardiac hypertrophy, placental distress, and small size were all indicative of anemia...
March 2016: American Journal of Pathology
Jantima Tanboon, Erik A Williams, David N Louis
A number of key mutations that affect treatment and prognosis have been identified in human gliomas. Two major ways to identify these mutations in a tumor sample are direct interrogation of the mutated DNA itself and immunohistochemistry to assess the effects of the mutated genes on proteins. Immunohistochemistry is an affordable, robust, and widely available technology that has been in place for decades. For this reason, the use of immunohistochemical approaches to assess molecular genetic changes has become an essential component of state-of-the-art practice...
January 2016: Journal of Neuropathology and Experimental Neurology
Daniel P Cahill, David N Louis, John Gregory Cairncross
Oligodendroglioma is the quintessential molecularly-defined brain tumor. The characteristic whole-arm loss of the long arm of chromosome 1 and the short arm of chromosome 19 (1p/19q-codeletion) within the genome of these tumors facilitated the reproducible molecular identification of this subcategory of gliomas. More recently, recurrent molecular genetic alterations have been identified to occur concurrently with 1p/19q-codeletion, and definitively identify these tumors, including mutations in IDH1/2, CIC, FUBP1, and the TERT promoter, as well as the absence of ATRX and TP53 alterations...
2015: CNS Oncology
Lei Yang, Jun-Ya Zhu, Jian-Guo Zhang, Bo-Jun Bao, Cheng-Qi Guan, Xiao-Jing Yang, Yan-Hua Liu, Yue-Jiao Huang, Run-Zhou Ni, Li-Li Ji
The human far upstream element (FUSE) binding protein 1 (FUBP1) belongs to an ancient family which is required for proper regulation of the c-Myc proto-oncogene. Although c-Myc plays an important role in development of various carcinomas, the relevance of FUBP1 and their contribution to esophageal squamous cell carcinoma (ESCC) development remain unclear. In this study, we aimed to investigate the relationship between FUBP1 and c-Myc as well as their contribution to ESCC development. Western blot and immunohistochemical analyses were performed to evaluate FUBP1 expression...
March 2016: Tumour Biology: the Journal of the International Society for Oncodevelopmental Biology and Medicine
Vijay Padul, Sridhar Epari, Aliasgar Moiyadi, Prakash Shetty, Neelam Vishwanath Shirsat
Oligodendrogliomas with combined loss of chromosome arms 1p and 19q are known to be particularly sensitive to chemotherapy, and the CIC gene located on 19q is known to be mutated in over 50% of the 1p/19q codeleted oligodendrogliomas. However, the role of CIC in the oligodendroglioma pathogenesis is not known. Exome sequencing of 11 oligodendroglial tumors identified 9 tumors with combined loss of 1p and 19q. Somatic mutations were found in the CIC and FUBP1 genes. Recurrent somatic mutations were also identified in the Notch signaling pathway genes NOTCH1 and MAML3, the chromatin modifying gene ARID1A and in KRAS...
December 2015: Genes, Chromosomes & Cancer
Hendrikus J Dubbink, Peggy N Atmodimedjo, Johan M Kros, Pim J French, Marc Sanson, Ahmed Idbaih, Pieter Wesseling, Roelien Enting, Wim Spliet, Cees Tijssen, Winand N M Dinjens, Thierry Gorlia, Martin J van den Bent
BACKGROUND: Histopathological diagnosis of diffuse gliomas is subject to interobserver variation and correlates modestly with major prognostic and predictive molecular abnormalities. We investigated a series of patients with locally diagnosed anaplastic oligodendroglial tumors included in the EORTC phase III trial 26951 on procarbazine/lomustine/vincristine (PCV) chemotherapy to explore the diagnostic, prognostic, and predictive value of targeted next-generation sequencing (NGS) in diffuse glioma and to assess the prognostic impact of FUBP1 and CIC mutations...
March 2016: Neuro-oncology
Aibo Huang, Hua Xu, Wenxu Hong, Zhixiong Zhuang, Jianjun Liu
OBJECTIVE: To put the insight into the trichloroethylene (TCE)-induced effect on the differential expression of subcellular proteins in human normal liver cell line (L-02). METHODS: The membrane proteins and nuclear proteins of TCE-treated (8.0 mmol/L) group and controls were extracted by subcellular proteome extraction kit, respectively. The TCE-induced differentially expressions were analyzed by a two-dimensional fluorescence difference gel electrophoresis (2D-DIGE) and matrix-assisted laser desorption/ionization tandem time-of-flight spectrometry (MALDI-TOF-MS)...
March 2015: Zhonghua Yu Fang Yi Xue za Zhi [Chinese Journal of Preventive Medicine]
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