DOCSLIB.ORG

Open Full Page

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
Open Full Page Research Article Distinct Genomic Profiles in Hereditary Breast Tumors Identified by Array-Based Comparative Genomic Hybridization Go¨ran Jo¨nsson,1 Tara L. Naylor,5 Johan Vallon-Christersson,1 Johan Staaf,1 Jia Huang,5 M. Renee Ward,5 Joel D. Greshock,5 Lena Luts,4 Ha˚kan Olsson,1 Nazneen Rahman,6 Michael Stratton,6 Markus Ringne´r,3 A˚ke Borg,1,2 and Barbara L. Weber5 1Department of Oncology, University Hospital; 2Lund Strategic Research Center for Stem Cell Biology and Cell Therapy and 3Department of Theoretical Physics, Lund University; and 4Department of Pathology, University Hospital, Lund, Sweden; 5Abramson Family Cancer Research Institute, University of Pennsylvania, Philadelphia, Pennsylvania; and 6Section of Cancer Genetics, Institute of Cancer Research, Sutton, Surrey, United Kingdom Abstract of additional predisposing genes, although technical limitations Mutations in BRCA1 and BRCA2 account for a significant and the complexity of BRCA gene regulation and mutation proportion of hereditary breast cancers. Earlier studies have spectrum can probably explain why some disease-causing muta- shown that inherited and sporadic tumors progress along tions are missed (2). BRCA1 and BRCA2 function as classic tumor different somatic genetic pathways and that global gene suppressor genes with frequent loss of the wild-type allele in expression profiles distinguish between these groups. To tumors of mutation carriers. The BRCA1 protein has been determine whether genomic profiles similarly discriminate implicated in a broad range of cellular functions, including repair among BRCA1, BRCA2, and sporadic tumors, we established of double-strand breaks by homologous recombination, cell cycle DNA copy number profiles using comparative genomic checkpoint control, chromatin remodeling, and transcriptional hybridization to BAC-clone microarrays providing <1 Mb regulation. The role of BRCA2 is more restricted to DNA resolution. Tumor DNA was obtained from BRCA1 (n = 14) and recombination and repair processes, being particular important BRCA2 (n = 12) mutation carriers, as well as sporadic cases in RAD51 regulation. It is thought that part of the tumor (n = 26). Overall, BRCA1 tumors had a higher frequency of suppressor function of BRCA1 and BRCA2 is attributed to this copy number alterations than sporadic breast cancers (P = genome caretaker activity (3). 0.00078). In particular, frequent losses on 4p, 4q, and 5q in Earlier studies have suggested different somatic genetic path- BRCA1 tumors and frequent gains on 7p and 17q24 in BRCA2 ways in progression of inherited and sporadic tumors, and several tumors distinguish these from sporadic tumors. Distinct histopathologic and clinical features differ among BRCA1, BRCA2, amplicons at 3q27.1-q27.3 were identified in BRCA1 tumors and sporadic breast cancers. For instance, BRCA1 tumors are often and at 17q23.3-q24.2 in BRCA2 tumors. A homozygous estrogen and progesterone receptor (ER/PR) negative, whereas deletion on 5q12.1 was found in a BRCA1 tumor. Using a set BRCA2 tumors predominantly are ER and PR positive (4–7). BRCA1 of 169 BAC clones that detect significantly (P < 0.001) different tumors are primarily of high histologic grade and manifest high frequencies of copy number changes in inherited and sporadic lymphocyte infiltration and continuous ‘‘pushing’’ tumor margins. tumors, these could be discriminated into separate groups BRCA2 tumors are more heterogeneous but have significantly less using hierarchical clustering. By comparing DNA copy number tubule formation compared with sporadic tumors, which account and RNA expression for genes in these regions, several for an overall higher histologic grade (7). Using global gene candidate genes affected by up- or down-regulation were expression profiling, we have previously identified a set of genes to identified. Moreover, using support vector machines, we distinguish among BRCA1, BRCA2, and sporadic tumors (8). In a correctly classified BRCA1 and BRCA2 tumors (P < 0.0000004 parallel fashion, we used conventional metaphase comparative ge- and 0.00005, respectively). Further validation may prove this nomic hybridization (CGH) to characterize chromosomal aberrations tumor classifier to be useful for selecting familial breast in hereditary breast tumors (9–11). We found a higher frequency of cancer cases for further mutation screening, particularly, as copy number alterations among BRCA1 and BRCA2 tumors when these data can be obtained using archival tissue. (Cancer Res compared with sporadic cases. BRCA1 tumors harbor frequent loss 2005; 65(17): 7612-21) at 2q, 4p, 4q, 5q, and 12q, whereas BRCA2 tumors are characterized by a higher frequency of 6q and 13q losses as well as gains on 17q22- Introduction 24 and 20q13. Others have also used metaphase CGH analysis to classify BRCA1 tumors based on patterns of genomic alterations and Germ line mutations in the two major breast cancer suscepti- suggested gain of 3q and loss of 3p and 5q to distinguish BRCA1 from bility genes, BRCA1 and BRCA2, confer a highly elevated risk of sporadic tumors (12). breast and ovarian cancer and account for a significant proportion Taken together, these findings imply that tumor profiling can be of inherited breast cancer (1). However, many familial breast cancer useful as diagnostics tools and encouraged us to extend our cases cannot be attributed to BRCA1 and BRCA2, suggesting a role previous studies with an array-based CGH technique, providing higher consistency and resolution, to build classifiers based on genomic aberration patterns in tumor tissue. In the familial cancer Requests for reprints: A˚ke Borg, Department of Oncology, Lund University, SE-221 clinic, candidates for BRCA1 and BRCA2 mutation screening are 85 Lund, Sweden, SE 22185. Phone: 46-46-177502; Fax: 46-46-147327; E-mail: ake.borg@ selected based on family history, age at onset, bilateral disease, and onk.lu.se. I2005 American Association for Cancer Research. cases of ovarian cancers in the family. Because screening of these doi:10.1158/0008-5472.CAN-05-0570 genes is laborious and costly, more precise criteria for selection and Cancer Res 2005; 65: (17). September 1, 2005 7612 www.aacrjournals.org Downloaded from cancerres.aacrjournals.org on September 26, 2021. © 2005 American Association for Cancer Research. Genomic Profiling of Hereditary Breast Cancer diagnosis is needed (e.g., a rationale corresponding to the tests for treatment before proteinase K digestion and phenol chloroform purifica- microsatellite instability and mismatch repair protein expression tion. For all samples, 1 Ag of genomic DNA was labeled according to in diagnosis of hereditary nonpolyposis colon cancer; ref. 13). In published protocols (14) using a random labeling kit (Invitrogen Life the present study, we established DNA copy number profiles for Technologies, Carlsbad, CA). Tumor DNA and male reference DNA was differentially labeled, pooled, mixed with human COT-1 DNA, dried down, BRCA1, BRCA2, and sporadic breast tumors using a microarray f and resuspended in a formamide-based buffer (14). The hybridization containing 5,000 individual BAC clones providing an average reactions were applied to arrays and the arrays were incubated under resolution of 1 Mbp. Furthermore, by comparing DNA copy number coverslips for 48 to 72 hours at 37jC. Slides were washed according to and gene expression in 11 BRCA1/2 tumors, we found novel published protocols (15) and scanned using an Axon 4000A scanner (Axon genes affected by genomic aberrations in hereditary breast cancer. Instruments, Wheatherford, TX). All experiments were done with ‘‘dye- Our results form the basis for a new classification system of swap’’ to account for variations in dye labeling efficiency and fluorescence inherited breast cancer and reveal new molecular targets in tumor emission and all BACs are spotted on the array in duplicate; thus, each data progression of inherited tumors. The approach of using array CGH point is represented by four replicates. in diagnostics may be more advantageous than gene expression RNA extraction and gene expression analysis. RNA was extracted profiling because paraffin-embedded material can be used and thus from freshly frozen tumor tissue using Trizol reagent (Invitrogen Life Technologies) followed by RNeasy Midi kit (Qiagen, Chatsworth, CA). RNA more feasible in the clinical setting. quality was assessed using the RNA 6000 Nano LabChip Kit for Agilent 2100 bioanalyzer (Agilent Technologies, Palo Alto, CA) and concentration was Materials and Methods determined using a NanoDrop Spectrophotometer (NanoDrop Technolo- Patients and tumors. Freshly frozen breast tumor tissue was obtained gies, Wilmington, DE). Arrays were produced by the SWEGENE DNA from the Southern Sweden Breast Cancer Group’s tissue bank at the Microarray Resource Centre, Department of Oncology at Lund University. Department of Oncology, Lund University Hospital and from the HWP and Human Genome Oligo Set Version 2.1 (containing 21,329 70-mer probes) Delaware Memorial Hospital. Breast cancer patients from which BRCA1 and and Human Genome Oligo Set Version 2.1 Upgrade (containing 5,462 70-mer BRCA2 tumors were derived had been screened for germ line mutations in probes) were obtained from Operon Biotechnologies, Inc. (Huntsville, AL). the BRCA1 and BRCA2 genes according to standard techniques (6). From cDNA synthesis, labeling, and cleanup were overall done according to Lund University Hospital, eight frozen BRCA1 tumors were obtained from manufacturers’ instructions
Load more

Recommended publications
  • Polyclonal Antibody to PDE4D - Aff - Purified
    OriGene Technologies, Inc. OriGene Technologies GmbH 9620 Medical Center Drive, Ste 200 Schillerstr. 5 Rockville, MD 20850 32052 Herford UNITED STATES GERMANY Phone: +1-888-267-4436 Phone: +49-5221-34606-0 Fax: +1-301-340-8606 Fax: +49-5221-34606-11 [email protected] [email protected] AP06558PU-N Polyclonal Antibody to PDE4D - Aff - Purified Alternate names: 5'-cyclic phosphodiesterase 4D, DPDE3, DPDE3, EC=3.1.4.17, PDE43, PDE4D, cAMP- specific 3' Quantity: 0.1 mg Concentration: 1.0 mg/ml Background: Phosphodiesterases (PDE) hydrolyze cAMP to 5’AMP and thus play a critical role in the regulation of intracellular cAMP. Division of the PDE superfamily by sequence homology and enzymatic properties yields 11 PDE families. A unique upstream conserved region (UCR) characterizes the PDE4 family. Four separate genes (A-D) encode the PDE4 enzymes, and alternative splicing generates short or long isoforms of each gene. Long PDE4 isoforms contain both UCR1 and UCR2 while short PDE4 isoforms possess only UCR2. Both UCR domains are necessary for dimerization of PDE4 isoforms. The human PDE4D gene maps to chromosome 5q12. The splice variants include isoforms PDE4D1-6. Uniprot ID: Q08499 NCBI: NP_001098101.1 GeneID: 5144 Host: Rabbit Immunogen: Synthetic peptide, corresponding to amino acids 30-70 Human PDE4D. Format: State: Liquid purified Ig fraction Purification: Affinity-chromatography using epitope-specific immunogen and the purity is > 95% (by SDS-PAGE) Buffer System: Phosphate buffered saline (PBS), pH 7.2. Preservatives: 15 mM sodium azide Applications: Western blot: 1/500-1/1000. Immunohistochemistry on paraffin sections: 1/50-1/200.
    [Show full text]
  • Supplementary Data
    SUPPLEMENTARY DATA A cyclin D1-dependent transcriptional program predicts clinical outcome in mantle cell lymphoma Santiago Demajo et al. 1 SUPPLEMENTARY DATA INDEX Supplementary Methods p. 3 Supplementary References p. 8 Supplementary Tables (S1 to S5) p. 9 Supplementary Figures (S1 to S15) p. 17 2 SUPPLEMENTARY METHODS Western blot, immunoprecipitation, and qRT-PCR Western blot (WB) analysis was performed as previously described (1), using cyclin D1 (Santa Cruz Biotechnology, sc-753, RRID:AB_2070433) and tubulin (Sigma-Aldrich, T5168, RRID:AB_477579) antibodies. Co-immunoprecipitation assays were performed as described before (2), using cyclin D1 antibody (Santa Cruz Biotechnology, sc-8396, RRID:AB_627344) or control IgG (Santa Cruz Biotechnology, sc-2025, RRID:AB_737182) followed by protein G- magnetic beads (Invitrogen) incubation and elution with Glycine 100mM pH=2.5. Co-IP experiments were performed within five weeks after cell thawing. Cyclin D1 (Santa Cruz Biotechnology, sc-753), E2F4 (Bethyl, A302-134A, RRID:AB_1720353), FOXM1 (Santa Cruz Biotechnology, sc-502, RRID:AB_631523), and CBP (Santa Cruz Biotechnology, sc-7300, RRID:AB_626817) antibodies were used for WB detection. In figure 1A and supplementary figure S2A, the same blot was probed with cyclin D1 and tubulin antibodies by cutting the membrane. In figure 2H, cyclin D1 and CBP blots correspond to the same membrane while E2F4 and FOXM1 blots correspond to an independent membrane. Image acquisition was performed with ImageQuant LAS 4000 mini (GE Healthcare). Image processing and quantification were performed with Multi Gauge software (Fujifilm). For qRT-PCR analysis, cDNA was generated from 1 µg RNA with qScript cDNA Synthesis kit (Quantabio). qRT–PCR reaction was performed using SYBR green (Roche).
    [Show full text]
  • Monoclonal Antibodies
    NOTE Clinical Pathology Establishment of rat anti-canine DEP domain containing 1B (DEPDC1B) monoclonal antibodies Masaya IGASE1), Yuki MORINAGA1), Masahiro KATO2), Toshihiro TSUKUI2), Yusuke SAKAI3), Masaru OKUDA4) and Takuya MIZUNO1)* 1)Laboratory of Molecular Diagnostics and Therapeutics, Joint Faculty of Veterinary Medicine, Yamaguchi University, 1677-1, Yoshida, Yamaguchi-shi, Yamaguchi 753-8511, Japan 2)Nippon Zenyaku Kogyo Co., Ltd., 1-1 Tairanoue, Sasagawa, Asaka-machi, Koriyama, Fukushima 963-0196, Japan 3)Laboratory of Veterinary Pathology, Joint Faculty of Veterinary Medicine, Yamaguchi University, 1677-1, Yoshida, Yamaguchi-shi, Yamaguchi 753-8511, Japan 4)Laboratory of Veterinary Internal Medicine, Joint Faculty of Veterinary Medicine, Yamaguchi University, 1677-1, Yoshida, Yamaguchi-shi, Yamaguchi 753-8511, Japan ABSTRACT. DEP domain-containing 1B (DEPDC1B) is involved in the regulation of cell de- J. Vet. Med. Sci. adhesion and actin cytoskeleton activity during the G2/M transition of the cell cycle, and its 82(4): 483–487, 2020 overexpression has been proven to be associated with cancer progression in several human cancers. Canine DEPDC1B was identified as a gene that was overexpressed in canine lymphoma doi: 10.1292/jvms.19-0667 tissues in our previous study. However, in dogs, the protein expression of DEPDC1B remains to be determined due to the lack of a specific monoclonal antibody. Here, we developed rat monoclonal antibodies against canine DEPDC1B and characterized their applicability for immunodetection Received: 12 December 2019 assays. Our findings demonstrated that these antibodies are functional and can be important tools Accepted: 20 February 2020 to investigate the precise role of DEPDC1B in canine tumors. Advanced Epub: 6 March 2020 KEY WORDS: antibody, cancer, DEP domain-containing 1B, dog The DEP domain-containing 1B (DEPDC1B) gene was recently identified and localized at human chromosome 5 (5q12.1).
    [Show full text]
  • Analysis of the Indacaterol-Regulated Transcriptome in Human Airway
    Supplemental material to this article can be found at: http://jpet.aspetjournals.org/content/suppl/2018/04/13/jpet.118.249292.DC1 1521-0103/366/1/220–236$35.00 https://doi.org/10.1124/jpet.118.249292 THE JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS J Pharmacol Exp Ther 366:220–236, July 2018 Copyright ª 2018 by The American Society for Pharmacology and Experimental Therapeutics Analysis of the Indacaterol-Regulated Transcriptome in Human Airway Epithelial Cells Implicates Gene Expression Changes in the s Adverse and Therapeutic Effects of b2-Adrenoceptor Agonists Dong Yan, Omar Hamed, Taruna Joshi,1 Mahmoud M. Mostafa, Kyla C. Jamieson, Radhika Joshi, Robert Newton, and Mark A. Giembycz Departments of Physiology and Pharmacology (D.Y., O.H., T.J., K.C.J., R.J., M.A.G.) and Cell Biology and Anatomy (M.M.M., R.N.), Snyder Institute for Chronic Diseases, Cumming School of Medicine, University of Calgary, Calgary, Alberta, Canada Received March 22, 2018; accepted April 11, 2018 Downloaded from ABSTRACT The contribution of gene expression changes to the adverse and activity, and positive regulation of neutrophil chemotaxis. The therapeutic effects of b2-adrenoceptor agonists in asthma was general enriched GO term extracellular space was also associ- investigated using human airway epithelial cells as a therapeu- ated with indacaterol-induced genes, and many of those, in- tically relevant target. Operational model-fitting established that cluding CRISPLD2, DMBT1, GAS1, and SOCS3, have putative jpet.aspetjournals.org the long-acting b2-adrenoceptor agonists (LABA) indacaterol, anti-inflammatory, antibacterial, and/or antiviral activity. Numer- salmeterol, formoterol, and picumeterol were full agonists on ous indacaterol-regulated genes were also induced or repressed BEAS-2B cells transfected with a cAMP-response element in BEAS-2B cells and human primary bronchial epithelial cells by reporter but differed in efficacy (indacaterol $ formoterol .
    [Show full text]
  • The Genetic Program of Pancreatic Beta-Cell Replication in Vivo
    Page 1 of 65 Diabetes The genetic program of pancreatic beta-cell replication in vivo Agnes Klochendler1, Inbal Caspi2, Noa Corem1, Maya Moran3, Oriel Friedlich1, Sharona Elgavish4, Yuval Nevo4, Aharon Helman1, Benjamin Glaser5, Amir Eden3, Shalev Itzkovitz2, Yuval Dor1,* 1Department of Developmental Biology and Cancer Research, The Institute for Medical Research Israel-Canada, The Hebrew University-Hadassah Medical School, Jerusalem 91120, Israel 2Department of Molecular Cell Biology, Weizmann Institute of Science, Rehovot, Israel. 3Department of Cell and Developmental Biology, The Silberman Institute of Life Sciences, The Hebrew University of Jerusalem, Jerusalem 91904, Israel 4Info-CORE, Bioinformatics Unit of the I-CORE Computation Center, The Hebrew University and Hadassah, The Institute for Medical Research Israel- Canada, The Hebrew University-Hadassah Medical School, Jerusalem 91120, Israel 5Endocrinology and Metabolism Service, Department of Internal Medicine, Hadassah-Hebrew University Medical Center, Jerusalem 91120, Israel *Correspondence: [email protected] Running title: The genetic program of pancreatic β-cell replication 1 Diabetes Publish Ahead of Print, published online March 18, 2016 Diabetes Page 2 of 65 Abstract The molecular program underlying infrequent replication of pancreatic beta- cells remains largely inaccessible. Using transgenic mice expressing GFP in cycling cells we sorted live, replicating beta-cells and determined their transcriptome. Replicating beta-cells upregulate hundreds of proliferation- related genes, along with many novel putative cell cycle components. Strikingly, genes involved in beta-cell functions, namely glucose sensing and insulin secretion were repressed. Further studies using single molecule RNA in situ hybridization revealed that in fact, replicating beta-cells double the amount of RNA for most genes, but this upregulation excludes genes involved in beta-cell function.
    [Show full text]
  • 1 Title the Role of Mitotic Cell-Substrate Adhesion Re
    Manuscript Title The role of mitotic cell-substrate adhesion re-modeling in animal cell division. Authors Christina L. Dix1*, Helen K. Matthews1*, Marina Uroz3, Susannah McLaren1, Lucie Wolf2, Nicholas Heatley1, Zaw Win1, Pedro Almada1, Ricardo Henriques1, Michael Boutros2, Xavier Trepat3,4,5,6 and Buzz Baum1,7 *These authors contributed equally Affiliations 1 MRC - Laboratory for Molecular Cell Biology, University College London, London WC1E 6BT, United Kingdom. 2 Division of Signaling and Functional Genomics, German Cancer Research Center (DKFZ), and Department for Cell and Molecular Biology, Medical Faculty Mannheim, Heidelberg University, 69120 Heidelberg, Germany 3 Institute for Bioengineering of Catalonia (IBEC), The Barcelona Institute for Science and Technology (BIST), 08028 Barcelona, Spain 4 Unitat de Biofisica i Bioenginyeria, Facultat de Medicina, Universitat de Barcelona, 08036 Barcelona, Spain 5 Institució Catalana de Recerca i Estudis Avançats (ICREA), 08010 Barcelona, Spain 6 Center for Networked Biomedical Research on Bioengineering, Biomaterials and Nanomedicine (CIBER-BBN), 08028 Barcelona, Spain 7 Institute for the Physics of Living Systems, University College London, London WC1E 6BT, United Kingdom. 1 Contact information of lead contact and corresponding author: [email protected] Summary Animal cells undergo a dramatic series of shape changes as they divide, which depend on re-modeling of cell-substrate adhesions. Here, we show that while focal adhesion complexes are disassembled during mitotic rounding, integrins remain in place. These integrin-rich contacts connect mitotic cells to the underlying substrate throughout mitosis, guide polarized cell migration following mitotic exit, and are functionally important, since adherent cells undergo division failure when removed from the substrate. Further, the ability of cells to re-spread along pre-existing adhesive contacts is essential for division in cells compromised in their ability to construct a RhoGEF- dependent (Ect2) actomyosin ring.
    [Show full text]
  • Eine Dokumentvorlage Für Abschlussarbeiten Und Andere Wissenschaftliche Arbeiten, Insbesondere Bachelorarbeiten, Masterarbeiten
    1 Institute of Animal Science University of Hohenheim Prof. Dr. Ludwig Hölzle Transcriptomic analyses during infectious anemia in pigs DISSERTATION submitted in fulfillment of the requirements for the degree “Doktor der Agrarwissenschaften” (Dr. sc. agr. / PhD in Agricultural Science) to the Faculty of Agricultural Sciences presented by Sarah-Lena Mack born in Stuttgart, Germany 2018 2 Die vorliegende Arbeit wurde am 03.04.2019 von der Fakultät Agrarwissenschaften der Universität Hohenheim als "Dissertation zur Erlangung des Grades eines Doktors der Agrarwissenschaften" angenommen (Datum: vgl. Schreiben des Vorsitzenden des Pro- motionsausschusses an den/die Doktoranden/in). Tag der mündlichen Prüfung: 20.05.2019 Leiter/in der Prüfung: Prof. Dr. Jörn Bennewitz Berichterstatter/in 1. Prüfer/in: Prof. Dr. Ludwig Hölzle Mitberichterstatter/in, 2. Prüfer/in: Prof. Dr. Holger Stefanski ggf. weitere Berichter/in bzw. Prüfer/in: Prof. Dr. Mathias Ritzmann < Hohenheim, 18.12.2018, Sarah-Lena Mack > 3 Für meine Eltern 4 Table of contents Table of contents ......................................................................................................... 4 Table of figures ............................................................................................................ 7 List of tables ................................................................................................................ 8 List of abbreviations ................................................................................................... 9 Overview
    [Show full text]
  • An Expanded Proteome of Cardiac T-Tubules☆
    Cardiovascular Pathology 42 (2019) 15–20 Contents lists available at ScienceDirect Cardiovascular Pathology Original Article An expanded proteome of cardiac t-tubules☆ Jenice X. Cheah, Tim O. Nieuwenhuis, Marc K. Halushka ⁎ Department of Pathology, Division of Cardiovascular Pathology, Johns Hopkins University SOM, Baltimore, MD, USA article info abstract Article history: Background: Transverse tubules (t-tubules) are important structural elements, derived from sarcolemma, found Received 27 February 2019 on all striated myocytes. These specialized organelles create a scaffold for many proteins crucial to the effective Received in revised form 29 April 2019 propagation of signal in cardiac excitation–contraction coupling. The full protein composition of this region is un- Accepted 17 May 2019 known. Methods: We characterized the t-tubule subproteome using 52,033 immunohistochemical images covering Keywords: 13,203 proteins from the Human Protein Atlas (HPA) cardiac tissue microarrays. We used HPASubC, a suite of Py- T-tubule fi Proteomics thon tools, to rapidly review and classify each image for a speci c t-tubule staining pattern. The tools Gene Cards, Caveolin String 11, and Gene Ontology Consortium as well as literature searches were used to understand pathways and relationships between the proteins. Results: There were 96 likely t-tubule proteins identified by HPASubC. Of these, 12 were matrisome proteins and 3 were mitochondrial proteins. A separate literature search identified 50 known t-tubule proteins. A comparison of the 2 lists revealed only 17 proteins in common, including 8 of the matrisome proteins. String11 revealed that 94 of 127 combined t-tubule proteins generated a single interconnected network. Conclusion: Using HPASubC and the HPA, we identified 78 novel, putative t-tubule proteins and validated 17 within the literature.
    [Show full text]
  • Exome Sequencing Identifies PDE4D Mutations As Another Cause of Acrodysostosis
    CORE Metadata, citation and similar papers at core.ac.uk Provided by Elsevier - Publisher Connector REPORT Exome Sequencing Identifies PDE4D Mutations as Another Cause of Acrodysostosis Caroline Michot,1,10 Carine Le Goff,1,10 Alice Goldenberg,2 Avinash Abhyankar,3 Ce´line Klein,1 Esther Kinning,4 Anne-Marie Guerrot,2 Philippe Flahaut,5 Alice Duncombe,6 Genevieve Baujat,1 Stanislas Lyonnet,1 Caroline Thalassinos,7 Patrick Nitschke,8 Jean-Laurent Casanova,3,9 Martine Le Merrer,1 Arnold Munnich,1 and Vale´rie Cormier-Daire1,* Acrodysostosis is a rare autosomal-dominant condition characterized by facial dysostosis, severe brachydactyly with cone-shaped epiph- yses, and short stature. Moderate intellectual disability and resistance to multiple hormones might also be present. Recently, a recurrent mutation (c.1102C>T [p.Arg368*]) in PRKAR1A has been identified in three individuals with acrodysostosis and resistance to multiple hormones. After studying ten unrelated acrodysostosis cases, we report here de novo PRKAR1A mutations in five out of the ten individ- uals (we found c.1102C>T [p.Arg368*] in four of the ten and c.1117T>C [p.Tyr373His] in one of the ten). We performed exome sequencing in two of the five remaining individuals and selected phosphodiesterase 4D (PDE4D) as a candidate gene. PDE4D encodes a class IV cyclic AMP (cAMP)-specific phosphodiesterase that regulates cAMP concentration. Exome analysis detected heterozygous PDE4D mutations (c.673C>A [p.Pro225Thr] and c.677T>C [p.Phe226Ser]) in these two individuals. Screening of PDE4D identified heterozygous mutations (c.568T>G [p.Ser190Ala] and c.1759A>C [p.Thr587Pro]) in two additional acrodysostosis cases.
    [Show full text]
  • Overexpressed DEPDC1B Contributes to the Progression of Hepatocellular Carcinoma by CDK1
    www.aging-us.com AGING 2021, Vol. 13, No. 16 Research Paper Overexpressed DEPDC1B contributes to the progression of hepatocellular carcinoma by CDK1 Xiao-Wei Dang1,*, Qi Pan2,*, Zhen-Hai Lin2,*, Hao-Hao Wang1, Lu-Hao Li1, Lin Li1, Dong-Qi Shen1, Pei-Ju Wang1 1Department of Hepatopancreatobiliary Surgery, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, China 2Department of Hepatic Surgery, The Cancer Hospital of Fudan University, Shanghai, China *Equal contribution Correspondence to: Xiao-Wei Dang; email: [email protected] Keywords: DEPDC1B, CDK1, proliferation, migration, hepatocellular carcinoma (HCC) Received: January 23, 2020 Accepted: February 16, 2021 Published: May 25, 2021 Copyright: © 2021 Dang et al. This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. ABSTRACT Background: Hepatocellular carcinoma (HCC) is the main type of primary liver cancer and shows a heavy burden worldwide. Its recurrence and mortality rate are still uncontrolled by the usage of present treatments. More attention has been focused on exploring specific genes that play important roles in HCC procession, and the function of DEP domain containing 1B (DEPDC1B) in HCC has not been researched. Methods: Immunohistochemical staining was used to detect the expression level of DEPDC1B in tumor tissues and adjacent normal tissues. After DEPDC1B and CDK1 knockdown in cell lines HEP3B2.1-7 and SK-HEP-1, MTT assay and colony formation assay was used to detect cell growth, flow cytometry assay was used to investigate cell apoptosis and cell cycle, wound-healing assay and Transwell assay were used to examine the tumor cell migration.
    [Show full text]
  • AB079. Upregulation of DEPDC1B Correlates with Tumor
    Translational Andrology and Urology, Vol 6, Suppl 3 August 2017 S243 Keywords: Prostate cancer (PCa); SPC25; prognosis; proliferation; cells via activating Wnt/β-catenin signaling. However, the cell cycle clinical relevance and functional roles of DEPDC1B in PCa remain unclear. In this study, we found that the expression doi: 10.21037/tau.2017.s078 levels of DEPDC1B in PCa tissues were significantly higher than that in non-tumor tissues. Furthermore, our results Cite this abstract as: Cui F, Hu J, Tan J, Tang H. Knockdown showed DEPDC1B was upregulated in high pathology of SPC25 inhibits cell proliferation and cycle progression in stage PCa. Kaplan-Meier analysis showed that Lower prostate cancer. Transl Androl Urol 2017;6(Suppl 3):AB078. DEPDC1B expression level was associated with better doi: 10.21037/tau.2017.s078 survival of PCa patients. GO and KEGG pathway analysis of DEPDC1B co-expressed genes showed DEPDC1B played an important role in regulating PCa proliferation and cell cycle progression. We believed that this study will provide a potential new therapeutic and prognostic target AB079. Upregulation of for prostate cancer. Keywords: Prostate cancer (PCa); DEPDC1B; prognosis; tumor DEPDC1B correlates with progression; cell tumor progression and predicts doi: 10.21037/tau.2017.s079 a poor prognosis in prostate Cite this abstract as: Cui F, Hu J, Tan J, Tang H. Upregulation cancer of DEPDC1B correlates with tumor progression and predicts a poor prognosis in prostate cancer. Transl Androl Urol 2017;6(Suppl 3):AB079. doi: 10.21037/tau.2017.s079 Feilun Cui, Jiangpeng Hu, Jian Tan, Huaming Tang Department of Urology, The Affiliated People’s Hospital of Jiangsu University, Zhenjiang 212000, China AB080.
    [Show full text]
  • Analysis of Structural Diversity in Wolf-Like Canids Reveals Post
    Ramirez et al. BMC Genomics 2014, 15:465 http://www.biomedcentral.com/1471-2164/15/465 RESEARCH ARTICLE Open Access Analysis of structural diversity in wolf-like canids reveals post-domestication variants Oscar Ramirez1, Iñigo Olalde1, Jonas Berglund2, Belen Lorente-Galdos1, Jessica Hernandez-Rodriguez1, Javier Quilez1, Matthew T Webster2, Robert K Wayne3, Carles Lalueza-Fox1, Carles Vilà4 and Tomas Marques-Bonet1,5,6* Abstract Background: Although a variety of genetic changes have been implicated in causing phenotypic differences among dogs, the role of copy number variants (CNVs) and their impact on phenotypic variation is still poorly understood. Further, very limited knowledge exists on structural variation in the gray wolf, the ancestor of the dog, or other closely related wild canids. Documenting CNVs variation in wild canids is essential to identify ancestral states and variation that may have appeared after domestication. Results: In this work, we genotyped 1,611 dog CNVs in 23 wolf-like canids (4 purebred dogs, one dingo, 15 gray wolves, one red wolf, one coyote and one golden jackal) to identify CNVs that may have arisen after domestication. We have found an increase in GC-rich regions close to the breakpoints and around 1 kb away from them suggesting that some common motifs might be associated with the formation of CNVs. Among the CNV regions that showed the largest differentiation between dogs and wild canids we found 12 genes, nine of which are related to two known functions associated with dog domestication; growth (PDE4D, CRTC3 and NEB) and neurological function (PDE4D, EML5, ZNF500, SLC6A11, ELAVL2, RGS7 and CTSB).
    [Show full text]