Review Article TBL1XR1 in Physiological and Pathological States
Total Page:16
File Type:pdf, Size:1020Kb
Load more
Recommended publications
-
Involvement of Corepressor Complex Subunit GPS2 in Transcriptional Pathways Governing Human Bile Acid Biosynthesis
Involvement of corepressor complex subunit GPS2 in transcriptional pathways governing human bile acid biosynthesis Sabyasachi Sanyal*†, Ann Båvner‡, Anna Haroniti§, Lisa-Mari Nilsson¶, Thomas Lunda˚ senʈ, Stefan Rehnmark‡, Michael Robin Witt‡, Curt Einarsson¶, Iannis Talianidis§, Jan-Åke Gustafsson*, and Eckardt Treuter*† *Department of Biosciences and Nutrition, Karolinska Institutet, ‡Karo Bio AB, ¶Department of Gastroenterology and Hepatology, and ʈDepartment of Endocrinology, Metabolism, and Diabetes, Karolinska University Hospital, S-14157 Huddinge, Sweden; and §Biomedical Sciences Research Center, Alexander Fleming, 16672 Vari, Athens, Greece Edited by David W. Russell, University of Texas Southwestern Medical Center, Dallas, TX, and approved August 16, 2007 (received for review July 18, 2007) Coordinated regulation of bile acid biosynthesis, the predominant histone methyltransferase (G9a) (ref. 15 and references therein). pathway for hepatic cholesterol catabolism, is mediated by few Here we identify GPS2 (G protein pathway suppressor 2), a key nuclear receptors including the orphan receptors liver receptor subunit of the NR corepressor (N-CoR) complex (16–18), as a homolog 1 (LRH-1), hepatocyte nuclear factor 4␣ (HNF4␣), small SHP cofactor that, by means of additional interactions with heterodimer partner (SHP), and the bile acid receptor FXR (farne- LRH-1, HNF4␣, and FXR, participates in the differential reg- soid X receptor). Activation of FXR initiates a feedback regulatory ulation of CYP7A1 and CYP8B1 expression in human liver cell loop via induction of SHP, which suppresses LRH-1- and HNF4␣- lines and primary human hepatocytes. Additionally, we provide dependent expression of cholesterol 7␣ hydroxylase (CYP7A1) and insights into the species- and gene-specific regulations of these sterol 12␣ hydroxylase (CYP8B1), the two major pathway enzymes. -
Mutation and Expression Analysis in Medulloblastoma Yields Prognostic
Bien-Willner and Mitra Acta Neuropathologica Communications 2014, 2:74 http://www.actaneurocomms.org/content/2/1/74 RESEARCH Open Access Mutation and expression analysis in medulloblastoma yields prognostic variants and a putative mechanism of disease for i17q tumors Gabriel A Bien-Willner1,2* and Robi D Mitra2 Abstract Current consensus identifies four molecular subtypes of medulloblastoma (MB): WNT, sonic hedgehog (SHH), and groups “3/C” and “4/D”. Group 4 is not well characterized, but harbors the most frequently observed chromosomal abnormality in MB, i17q, whose presence may confer a worse outcome. Recent publications have identified mutations in chromatin remodeling genes that may be overrepresented in this group, suggesting a biological role for these genes in i17q. This work seeks to explore the pathology that underlies i17q in MB. Specifically, we examine the prognostic significance of the previously-identified gene mutations in an independent set of MBs as well as to examine biological relevance of these genes and related pathways by gene expression profiling. The previously-implicated p53 signaling pathway is also examined as a putative driver of i17q tumor oncogenesis. The data show gene mutations associated with i17q tumors in previous studies (KMD6A, ZMYM3, MLL3 and GPS2) were correlated with significantly worse outcomes despite not being specific to i17q in this set. Expression of these genes did not appear to underlie the biology of the molecular variants. TP53 expression was significantly reduced in i17q/ group 4 tumors; this could not be accounted for by dosage effects alone. Expression of regulators and mediators of p53 signaling were significantly altered in i17q tumors. -
Applying Expression Profile Similarity for Discovery of Patient-Specific
bioRxiv preprint doi: https://doi.org/10.1101/172015; this version posted September 17, 2017. The copyright holder for this preprint (which was not certified by peer review) is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under aCC-BY 4.0 International license. Applying expression profile similarity for discovery of patient-specific functional mutations Guofeng Meng Partner Institute of Computational Biology, Yueyang 333, Shanghai, China email: [email protected] Abstract The progress of cancer genome sequencing projects yields unprecedented information of mutations for numerous patients. However, the complexity of mutation profiles of patients hinders the further understanding of mechanisms of oncogenesis. One basic question is how to uncover mutations with functional impacts. In this work, we introduce a computational method to predict functional somatic mutations for each of patient by integrating mutation recurrence with similarity of expression profiles of patients. With this method, the functional mutations are determined by checking the mutation enrichment among a group of patients with similar expression profiles. We applied this method to three cancer types and identified the functional mutations. Comparison of the predictions for three cancer types suggested that most of the functional mutations were cancer-type-specific with one exception to p53. By checking prediction results, we found that our method effectively filtered non-functional mutations resulting from large protein sizes. In addition, this methods can also perform functional annotation to each patient to describe their association with signalling pathways or biological processes. In breast cancer, we predicted "cell adhesion" and other mutated gene associated terms to be significantly enriched among patients. -
A Strategic Research Alliance: Turner Syndrome and Sex Differences
A strategic research alliance: Turner syndrome and sex differences The MIT Faculty has made this article openly available. Please share how this access benefits you. Your story matters. Citation Roman, Adrianna K. San and David C. Page. “A strategic research alliance: Turner syndrome and sex differences.” American journal of medical genetics. Part C, Seminars in medical genetics 181 (2019): 59-67 © 2019 The Author(s) As Published 10.1002/AJMG.C.31677 Publisher Wiley Version Author's final manuscript Citable link https://hdl.handle.net/1721.1/125103 Terms of Use Creative Commons Attribution-Noncommercial-Share Alike Detailed Terms http://creativecommons.org/licenses/by-nc-sa/4.0/ HHS Public Access Author manuscript Author ManuscriptAuthor Manuscript Author Am J Med Manuscript Author Genet C Semin Manuscript Author Med Genet. Author manuscript; available in PMC 2019 March 12. Published in final edited form as: Am J Med Genet C Semin Med Genet. 2019 March ; 181(1): 59–67. doi:10.1002/ajmg.c.31677. A strategic research alliance: Turner syndrome and sex differences Adrianna K. San Roman1 and David C. Page1,2,3 1Whitehead Institute, Cambridge, MA 02142, USA 2Howard Hughes Medical Institute, Whitehead Institute, Cambridge, MA 02142 3Department of Biology, Massachusetts Institute of Technology, Cambridge, MA 02139 Abstract Sex chromosome constitution varies in the human population, both between the sexes (46,XX females and 46,XY males), and within the sexes (for example, 45,X and 46,XX females, and 47,XXY and 46,XY males). Coincident with this genetic variation are numerous phenotypic differences between males and females, and individuals with sex chromosome aneuploidy. -
Deletions of IKZF1 and SPRED1 Are Associated with Poor Prognosis in A
Leukemia (2014) 28, 302–310 & 2014 Macmillan Publishers Limited All rights reserved 0887-6924/14 www.nature.com/leu ORIGINAL ARTICLE Deletions of IKZF1 and SPRED1 are associated with poor prognosis in a population-based series of pediatric B-cell precursor acute lymphoblastic leukemia diagnosed between 1992 and 2011 L Olsson1, A Castor2, M Behrendtz3, A Biloglav1, E Forestier4, K Paulsson1 and B Johansson1,5 Despite the favorable prognosis of childhood acute lymphoblastic leukemia (ALL), a substantial subset of patients relapses. As this occurs not only in the high risk but also in the standard/intermediate groups, the presently used risk stratification is suboptimal. The underlying mechanisms for treatment failure include the presence of genetic changes causing insensitivity to the therapy administered. To identify relapse-associated aberrations, we performed single-nucleotide polymorphism array analyses of 307 uniformly treated, consecutive pediatric ALL cases accrued during 1992–2011. Recurrent aberrations of 14 genes in patients who subsequently relapsed or had induction failure were detected. Of these, deletions/uniparental isodisomies of ADD3, ATP10A, EBF1, IKZF1, PAN3, RAG1, SPRED1 and TBL1XR1 were significantly more common in B-cell precursor ALL patients who relapsed compared with those remaining in complete remission. In univariate analyses, age (X10 years), white blood cell counts (4100 Â 109/l), t(9;22)(q34;q11), MLL rearrangements, near-haploidy and deletions of ATP10A, IKZF1, SPRED1 and the pseudoautosomal 1 regions on Xp/Yp were significantly associated with decreased 10-year event-free survival, with IKZF1 abnormalities being an independent risk factor in multivariate analysis irrespective of the risk group. Older age and deletions of IKZF1 and SPRED1 were also associated with poor overall survival. -
Central Hypothyroidism and Novel Clinical Phenotypes in Hemizygous Truncation of TBL1X
ISSN 2472-1972 Central Hypothyroidism and Novel Clinical Phenotypes in Hemizygous Truncation of TBL1X Marta García,1 Ana C. Barreda-Bonis,2 Paula Jiménez,1 Ignacio Rabanal,3 Arancha Ortiz,4 Elena Vallespín,5 Angela´ del Pozo,6 Juan Martínez-San Millan, ´ 7 Isabel Gonzalez-Casado, ´ 2 and José C. Moreno1 1Thyroid Molecular Laboratory, Institute for Medical and Molecular Genetics (INGEMM), La Paz University Hospital, Autonomous University of Madrid, 28046 Madrid, Spain; 2Pediatric Endocrinology, La Paz University Hospital, 28046 Madrid, Spain; 3Pediatric Otorhinolaryngology, La Paz University Hospital, 28046 Madrid, Spain; 4Child and Adolescent Psychiatry, La Paz University Hospital, 28046 Madrid, Spain; 5Functional and Structural Genomics, Institute for Medical and Molecular Genetics (INGEMM), La Paz University Hospital, 28046 Madrid, Spain; 6Bioinformatics Unit, Institute for Medical and Molecular Genetics (INGEMM), La Paz University Hospital, 28046 Madrid, Spain; and 7Department of Radiology, Ram´on y Cajal Hospital, 28039 Madrid, Spain ORCiD numbers: 0000-0003-0427-2751 (M. Garcı´a); 0000-0001-5664-5308 (J. C. Moreno). Transducin b-like 1 X-linked (TBL1X) gene encodes a subunit of the nuclear corepressor-silencing mediator for retinoid and thyroid hormone receptor complex (NCoR-SMRT) involved in repression of thyroid hormone action in the pituitary and hypothalamus. TBL1X defects were recently associated with central hypo- thyroidism and hearing loss. The current study aims to describe the clinical and genetic characterization of a male diagnosed with central hypothyroidism through thyroid hormone profiling, TRH test, brain MRI, audiometry, and psychological evaluation. Next-generation sequencing of known genes involved in thyroid disorders was implemented. The 6-year-old boy was diagnosed with central hypothyroidism [free T4: 10.42 pmol/L (normal: 12 to 22 pmol/L); TSH: 1.57 mIU/L (normal: 0.7 to 5.7 mIU/L)], with a mildly reduced TSH response to TRH. -
The Heterogeneous Landscape of ALK Negative ALCL
The heterogeneous landscape of ALK negative ALCL The Harvard community has made this article openly available. Please share how this access benefits you. Your story matters Citation Mereu, Elisabetta, Elisa Pellegrino, Irene Scarfò, Giorgio Inghirami, and Roberto Piva. 2017. “The heterogeneous landscape of ALK negative ALCL.” Oncotarget 8 (11): 18525-18536. doi:10.18632/ oncotarget.14503. http://dx.doi.org/10.18632/oncotarget.14503. Published Version doi:10.18632/oncotarget.14503 Citable link http://nrs.harvard.edu/urn-3:HUL.InstRepos:32630507 Terms of Use This article was downloaded from Harvard University’s DASH repository, and is made available under the terms and conditions applicable to Other Posted Material, as set forth at http:// nrs.harvard.edu/urn-3:HUL.InstRepos:dash.current.terms-of- use#LAA www.impactjournals.com/oncotarget/ Oncotarget, 2017, Vol. 8, (No. 11), pp: 18525-18536 Review The heterogeneous landscape of ALK negative ALCL Elisabetta Mereu1, Elisa Pellegrino1, Irene Scarfò2, Giorgio Inghirami1,3 and Roberto Piva1 1 Department of Molecular Biotechnology and Health Sciences, Center for Experimental Research and Medical Studies, University of Torino, Torino, Italy 2 Massachusetts General Hospital Cancer Center, Harvard Medical School, Boston, MA, USA 3 Department of Pathology and Laboratory Medicine, Weill Cornell Medical College, New York, NY, USA Correspondence to: Roberto Piva, email: [email protected] Keywords: anaplastic large cell lymphoma, molecular classification, therapy, ALK negative Received: October 11, 2016 Accepted: December 27, 2016 Published: January 04, 2017 ABSTRACT Anaplastic Large Cell Lymphoma (ALCL) is a clinical and biological heterogeneous disease including systemic ALK positive and ALK negative entities. Whereas ALK positive ALCLs are molecularly characterized and readily diagnosed, specific immunophenotypic or genetic features to define ALK negative ALCL are missing, and their distinction from other T-cell non-Hodgkin lymphomas (T-NHLs) can be controversial. -
Comprehensive Genome and Transcriptome Analysis Reveals Genetic Basis for Gene Fusions in Cancer
bioRxiv preprint doi: https://doi.org/10.1101/148684; this version posted June 12, 2017. The copyright holder for this preprint (which was not certified by peer review) is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under aCC-BY-NC-ND 4.0 International license. Comprehensive genome and transcriptome analysis reveals genetic basis for gene fusions in cancer Nuno A. Fonseca1*, Yao He2*, Liliana Greger1, PCAWG3, Alvis Brazma1, Zemin Zhang2 1 European Molecular Biology Laboratory, European Bioinformatics Institute (EMBL-EBI), Wellcome Trust Genome Campus, Hinxton, Cambridge CB10 1SD, UK; 2 Peking-Tsinghua Centre for Life Sciences, BIOPIC, and Beijing Advanced Innovation Centre for Genomics, Peking University, Beijing, 100871, China *Joint first authors Gene fusions are an important class of cancer-driving events with therapeutic and diagnostic values, yet their underlying genetic mechanisms have not been systematically characterized. Here by combining RNA and whole genome DNA sequencing data from 1188 donors across 27 cancer types we obtained a list of 3297 high-confidence tumour-specific gene fusions, 82% of which had structural variant (SV) support and 2372 of which were novel. Such a large collection of RNA and DNA alterations provides the first opportunity to systematically classify the gene fusions at a mechanistic level. While many could be explained by single SVs, numerous fusions involved series of structural rearrangements and thus are composite fusions. We discovered 75 fusions of a novel class of inter-chromosomal composite fusions, termed bridged fusions, in which a third genomic location bridged two different genes. -
HDAC3: Taking the SMRT-N-Correct Road to Repression
Oncogene (2007) 26, 5439–5449 & 2007 Nature Publishing Group All rights reserved 0950-9232/07 $30.00 www.nature.com/onc REVIEW HDAC3: taking the SMRT-N-CoRrect road to repression P Karagianni and J Wong1 Department of Molecular and Cellular Biology, Baylor College of Medicine, One Baylor Plaza, Houston, TX, USA Known histone deacetylases (HDACs) are divided into repression when targeted to promoters, as well as different classes, and HDAC3 belongs to Class I. Through physical association with the DNA-binding factor forming multiprotein complexes with the corepressors YY1 (Yang et al., 1997; Dangond et al., 1998; Emiliani SMRT and N-CoR, HDAC3 regulates the transcription et al., 1998). Together, these findings suggested that this of a plethora of genes. A growing list of nonhistone ubiquitously expressed protein could be involved in the substrates extends the role of HDAC3 beyond transcrip- regulation of mammalian gene expression. On the other tional repression. Here, we review data on the composi- hand, HDAC3 contains an intriguingly variable C tion, regulation and mechanism of action of the SMRT/ terminus, with no apparent similarity with other N-CoR-HDAC3 complexes and provide several examples HDACs. This observation led to the hypothesis that of nontranscriptional functions, to illustrate the wide HDAC3 may have some unique properties and may variety of physiological processes affected by this deacety- not be completely redundant with the other HDACs lase. Furthermore, we discuss the implication of HDAC3 (Yang et al., 1997). This is also suggested by the in cancer, focusing on leukemia. We conclude with some differential localization of HDAC3, which, unlike the thoughts about the potential therapeutic efficacies of predominantly nuclear HDACs 1 and 2, can be found in HDAC3 activity modulation. -
Fusion of the TBL1XR1 and HMGA1 Genes in Splenic Hemangioma with T(3;6)(Q26;P21)
1242 INTERNATIONAL JOURNAL OF ONCOLOGY 48: 1242-1250, 2016 Fusion of the TBL1XR1 and HMGA1 genes in splenic hemangioma with t(3;6)(q26;p21) IOANNIS PANAGOPOULOS1,2, LUDMILA GORUNOVA1,2, BODIL BJERKEHAGEN3, INGVILD LOBMAIER3 and SVERRE HEIM1,2,4 1Section for Cancer Cytogenetics, Institute for Cancer Genetics and Informatics, The Norwegian Radium Hospital, Oslo University Hospital; 2Centre for Cancer Biomedicine, Faculty of Medicine, University of Oslo; 3Department of Pathology, The Norwegian Radium Hospital, Oslo University Hospital; 4Faculty of Medicine, University of Oslo, Oslo, Norway Received September 27, 2015; Accepted November 26, 2015 DOI: 10.3892/ijo.2015.3310 Abstract. RNA-sequencing of a splenic hemangioma with 0.03-14% found in large autopsy series (1,2). In the vast majority the karyotype 45~47,XX,t(3;6)(q26;p21) showed that this of cases, splenic hemangiomas are incidental surgical, radio- translocation generated a chimeric TBL1XR1-HMGA1 gene. logic, or autopsy findings, made during evaluation for other This is the first time that this tumor has been subjected disorders (1-3). Arber et al (3) reported 7 localized splenic to genetic analysis, but the finding of an acquired clonal hemangiomas all of which were discovered incidentally in chromosome abnormality in cells cultured from the lesion surgical patients. In a large series of 32 patients with splenic and the presence of the TBL1XR1-HMGA1 fusion in them hemangioma, only 6 presented with abdominal symptoms and strongly favor the conclusion that splenic hemangiomas are only 4 had a palpable spleen (1). of a neoplastic nature. Genomic PCR confirmed the presence Because of the general absence of presenting symptoms of the TBL1XR1-HMGA1 fusion gene, and RT-PCR together and the typically incidental nature of splenic hemangiomas, the with Sanger sequencing verified the presence of the fusion age at presentation varies considerably. -
GPS2/KDM4A Pioneering Activity Regulates Promoter-Specific Recruitment of Pparg
Cell Reports Article GPS2/KDM4A Pioneering Activity Regulates Promoter-Specific Recruitment of PPARg M. Dafne Cardamone,1 Bogdan Tanasa,2 Michelle Chan,1 Carly T. Cederquist,1 Jaclyn Andricovich,1,4 Michael G. Rosenfeld,2,3 and Valentina Perissi1,* 1Biochemistry Department, Boston University School of Medicine, 72 East Concord Street, Boston, MA 02118, USA 2Department of Medicine, University of California, San Diego, School of Medicine, 9500 Gilman Drive, La Jolla, CA 92093, USA 3Howard Hughes Medical Institute, University of California, San Diego, School of Medicine, 9500 Gilman Drive, La Jolla, CA 92093, USA 4Present address: Department of Anatomy and Regenerative Biology, George Washington University, School of Medicine and Health Sciences, 2300 I Street NW, Washington, DC 20037, USA *Correspondence: [email protected] http://dx.doi.org/10.1016/j.celrep.2014.05.041 This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/3.0/). SUMMARY nfeld, 2005; Hager et al., 2009). Among the nuclear receptors, the peroxisome proliferator-activator receptors (PPARs) and Timely and selective recruitment of transcription liver X receptors (LXRs) are critical for the development and factors to their appropriate DNA-binding sites repre- the functional regulation of key metabolic organs, the adipose sents a critical step in regulating gene activation; tissue and the liver, respectively, with both receptors forming however, the regulatory strategies underlying each functional heterodimers with the retinoid X receptor (RXR). factor’s effective recruitment to specific promoter PPARg, in particular, is known as the master regulator of adipo- and/or enhancer regions are not fully understood. cyte differentiation and a critical factor for the regulation of lipid metabolism, immunity, and insulin sensitivity (Rosen and Spie- Here, we identify an unexpected regulatory mecha- gelman, 2001; Hong and Tontonoz, 2008; Sonoda et al., 2008). -
Recurrent Mutations of MYD88 and TBL1XR1 in Primary Central Nervous System Lymphomas
Published OnlineFirst July 26, 2012; DOI: 10.1158/1078-0432.CCR-12-0845 Clinical Cancer Human Cancer Biology Research Recurrent Mutations of MYD88 and TBL1XR1 in Primary Central Nervous System Lymphomas Alberto Gonzalez-Aguilar1,2, Ahmed Idbaih1,2, Blandine Boisselier2, Naïma Habbita2, Marta Rossetto2, Alice Laurenge2, Aurelie Bruno2, Anne Jouvet5, Marc Polivka3, Clovis Adam7, Dominique Figarella-Branger8, Catherine Miquel4, Anne Vital9, Herve Ghesquieres 6,Remy Gressin11, Vincent Delwail12, Luc Taillandier13, Olivier Chinot8, Pierre Soubeyran10, Emmanuel Gyan14, Sylvain Choquet1, Caroline Houillier2, Carole Soussain15, Marie-Laure Tanguy2, Yannick Marie2, Karima Mokhtari1,2, and Khe^ Hoang-Xuan1,2 Abstract Purpose: Our objective was to identify the genetic changes involved in primary central nervous system lymphoma (PCNSL) oncogenesis and evaluate their clinical relevance. Experimental Design: We investigated a series of 29 newly diagnosed, HIV-negative, PCNSL patients using high-resolution single-nucleotide polymorphism (SNP) arrays (n ¼ 29) and whole-exome sequencing (n ¼ 4) approaches. Recurrent homozygous deletions and somatic gene mutations found were validated by quantitative real-time PCR and Sanger sequencing, respectively. Molecular results were correlated with prognosis. Results: All PCNSLs were diffuse large B-cell lymphomas, and the patients received chemotherapy without radiotherapy as initial treatment. The SNP analysis revealed recurrent large and focal chromosome imbalances that target candidate genes in PCNSL oncogenesis. The most frequent genomic abnormalities were (i) 6p21.32 loss (HLA locus), (ii) 6q loss, (iii) CDKN2A homozygous deletions, (iv) 12q12-q22, and (v) chromosome 7q21 and 7q31 gains. Homozygous deletions of PRMD1, TOX, and DOCK5 and the amplification of HDAC9 were also detected. Sequencing of matched tumor and blood DNA samples identified novel somatic mutations in MYD88 and TBL1XR1 in 38% and 14% of the cases, respectively.