DOCSLIB.ORG

A DNA Methylation Prognostic Signature of Glioblastoma: Identification of NPTX2-PTEN-NF-Kb Nexus

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
A DNA Methylation Prognostic Signature of Glioblastoma: Identification of NPTX2-PTEN-NF-Kb Nexus Published OnlineFirst September 27, 2013; DOI: 10.1158/0008-5472.CAN-13-0298 Cancer Integrated Systems and Technologies Research A DNA Methylation Prognostic Signature of Glioblastoma: Identification of NPTX2-PTEN-NF-kB Nexus Sudhanshu Shukla1, Irene Rosita Pia Patric1, Sivaarumugam Thinagararjan1, Sujaya Srinivasan1, Baisakhi Mondal1, Alangar S. Hegde2, Bangalore A. Chandramouli3, Vani Santosh4, Arimappamagan Arivazhagan3, and Kumaravel Somasundaram1 Abstract Glioblastoma (GBM) is the most common, malignant adult primary tumor with dismal patient survival, yet the molecular determinants of patient survival are poorly characterized. Global methylation profile of GBM samples (our cohort; n ¼ 44) using high-resolution methylation microarrays was carried out. Cox regression analysis identified a 9-gene methylation signature that predicted survival in GBM patients. A risk-score derived from methylation signature predicted survival in univariate analysis in our and The Cancer Genome Atlas (TCGA) cohort. Multivariate analysis identified methylation risk score as an independent survival predictor in TCGA cohort. Methylation risk score stratified the patients into low-risk and high-risk groups with significant survival difference. Network analysis revealed an activated NF-kB pathway association with high-risk group. NF-kB inhibition reversed glioma chemoresistance, and RNA interference studies identified interleukin-6 and intercellular adhesion molecule- 1 as key NF-kB targets in imparting chemoresistance. Promoter hypermethylation of neuronal pentraxin II (NPTX2), a risky methylated gene, was confirmed by bisulfite sequencing in GBMs. GBMs and glioma cell lines had low levels of NPTX2 transcripts, which could be reversed upon methylation inhibitor treatment. NPTX2 over- expression induced apoptosis, inhibited proliferation and anchorage-independent growth, and rendered glioma cells chemosensitive. Furthermore, NPTX2 repressed NF-kB activity by inhibiting AKT through a p53-PTEN- dependent pathway, thus explaining the hypermethylation and downregulation of NPTX2 in NF-kB-activated high- risk GBMs. Taken together, a 9-gene methylation signature was identified as an independent GBM prognosticator and could be used for GBM risk stratification. Prosurvival NF-kB pathway activation characterized high-risk patients with poor prognosis, indicating it to be a therapeutic target. Cancer Res; 73(22); 1–11. Ó2013 AACR. Introduction drogenase 1 (IDH1) mutation status, and Glioma-CpG Island fi The grade IV glioma (glioblastoma; GBM) is the most Methylator Phenotype (G-CIMP) have been identi ed as GBM common, malignant primary brain tumor in adults. The prog- prognostic indicators (1, 8, 9). fi fi nosis remains poor with median survival ranging from 12 to 15 Expression pro ling studies have identi ed mRNA and fi months in spite of improvements in treatment protocol (1). microRNA signatures for classi cation and prognosis in GBM – Genetic heterogeneity in GBM has been proposed to explain (10 14). However, none of the gene signatures have been the limitations in the effectiveness of current therapies, which translated into clinics, suggesting the need for more robust fi necessitates the need for prognostic gene signature (2). Many prognostic gene signature panels. Here, we have identi ed and genetic and epigenetic alterations as well as expression of some validated a 9-gene methylation signature for GBM prognosti- genes have been correlated with poor or better prognosis (3–7). cation. Multivariate analysis with all known prognostic mar- fi In addition, molecular biomarkers like methyl guanine methyl kers and signatures for GBM identi ed our methylation sig- transferase (MGMT) promoter methylation, isocitrate dehy- nature to be an independent GBM prognostic indicator. Fur- thermore, an activated NF-kB pathway was found to be associated with poor prognosis. We also show that neuronal Authors' Affiliations: 1Department of Microbiology and Cell Biology, pentraxin II (NPTX2), a component of methylation signature Indian Institute of Science; 2Sri SatyaSai Institute of Higher Medical with risky methylation, inhibits cell growth by antagonizing 3 4 Sciences; Departments of Neurosurgery and Neuropathology, National NF-kB pathway through p53-PTEN activation, thus connecting Institute of Mental Health and Neuro Sciences, Bangalore, India the methylation signature to NF-kB pathway. Note: Supplementary data for this article are available at Cancer Research Online (http://cancerres.aacrjournals.org/). Materials and Methods Corresponding Author: Kumaravel Somasundaram, Department of Microbiology and Cell Biology, Indian Institute of Science, Bangalore Plasmids and reporter constructs 560012, India. Phone: 91-80-23607171; Fax: 91-80-23602697; E-mail: pCMV-Entry/NPTX2 was obtained from Origene. CAPI3K [email protected] (pCDNA3-CD2p110myc) was described earlier (15, 16). CAAKT doi: 10.1158/0008-5472.CAN-13-0298 (pCDNA MYR HA AKT1) was from Addgene (Plasmid 9008). Ó2013 American Association for Cancer Research. PG13-Luc was described earlier (17). CAIKK, NF-kB-Luc, www.aacrjournals.org OF1 Downloaded from cancerres.aacrjournals.org on October 1, 2021. © 2013 American Association for Cancer Research. Published OnlineFirst September 27, 2013; DOI: 10.1158/0008-5472.CAN-13-0298 Shukla et al. PTEN-luc, shATM, and shATR plasmid constructs were target genes were used to generate an interaction network obtained from Profs. I. Verma, K.N. Balaji, Dr. R.C.M. Simmen, using STRING database (19) using "experiment," "textmining," Dr. Y. Shiloh, and Dr. T. De Lange, respectively. and 0.700 confidence level as input option. To make a protein– protein interaction network, STRING curates publically avail- Cell lines and reagents able databases for the information on direct and indirect Temozolomide, adriamycin, 5-aza-20-deoxycytidine, MTT, functional protein interactions. The data file of protein–pro- and EscortIII transfection reagent were purchased from Sigma. tein interaction network generated from STRING was then Glioma cell lines U138, LN18, U343, LN229, U251, U87, T98G, used in Medusa software (20) to construct a network. This U373 (all human glioma derived), 293, and C6 (Rat glioma network was then analyzed by ViaComplex software (21). derived) were obtained from the laboratory of Dr. A. Guha, ViaComplex plots the gene expression activity over the Medusa University of Toronto, Toronto, Canada, and grown in DMEM network topology. ViaCompex overlays expression data with medium. SVG cells were obtained from Dr. P. Seth, National the interaction network and constructs a landscape graph by Brain Research Center, New Delhi, and grown in MEM medi- distributing microarray signal with interaction network coor- um. The medium was supplemented with 10% FBS, penicillin, dinates. For each gene, the average of each group (high-risk and and streptomycin. No information is available about their low-risk) was plotted over the average of the same gene in authentication, although many common known mutations/ normal brain and landscape was constructed. alterations have been verified in our laboratory. Other methods and additional information Patient samples and clinical data The details for additional clinical data, genomic DNA extrac- Tumor samples used for study were obtained from patients tion, sodium bisulfite conversion, methylation array analysis, who were operated at Sri Sathya Sai Institute of Higher Medical bisulfite sequencing, RNA isolation, real-time quantitative Sciences and National Institute of Mental Health and Neuro- RT-PCR analysis, 5-Aza-2'-deoxycytidine treatment, transfec- sciences, Bangalore, India. Normal brain tissue samples (ante- tion, colony formation assays, stable cell line generation, rior temporal lobe) obtained during surgery for intractable proliferation assay, cytotoxicity assay, CHIP assay, and PTEN epilepsy were used as control samples. Tissues were bisected activity ELISA are given in the Supplementary information. and one half was snap-frozen in liquid nitrogen and stored at À80C until DNA/RNA isolation. The other half was fixed in Statistical analysis formalin and processed for paraffin sections. These sections To identify the CpGs whose methylation correlates with were used for the histopathologic grading of tumor and survival, methylation data, available for 44 patients, were immunohistochemical staining. considered for survival analysis. The probes with missing value imputed using k nearest neighbor algorithm using Network analysis Imputation package in R. The assessment of survival correla- To find out the key signaling pathways differently regulat- tion for all 27,578 probes was performed using BRB-Array- ed between low-risk and high-risk patients, we compared gene Tools survival analysis (BRB-ArrayTools is available without expression profiles of The Cancer Genome Atlas (TCGA) data charge for non-commercial applications at http://linus.nci. set (Agilent expression data, 17,814 genes) with gene expression nih.gov/BRB-ArrayTools.html). Firstly, for each CpG probe, differences between low-risk and high-risk groups by conduct- univariate Cox proportional hazard regression was done and ing t-test analysis with FDR correction. We identified 3,127 parametric P value was calculated. The survival time and genes that were significantly differentially regulated between censoring status were randomly assigned to each patient the high-risk and low-risk groups (1,983 genes upregulated and and univariate Cox proportional hazard regression was 1,144 genes were downregulated in high-risk
Load more

Recommended publications
  • Scheme of Instruction 2018-19
    Scheme of Instruction 2018-19 Contents A. Scheme of Instruction Course Page No. Prefix Preface 3 I Division of Biological Sciences Preface 6 Integrated Ph D Programme in Biological Sciences DB 7 Biochemistry BC 10 Ecological Sciences EC 13 Molecular Biophysics MB 15 Microbiology and Cell Biology MC 20 Molecular Reproduction, Development and Genetics RD 24 Neuroscience NS 26 II Division of Chemical Sciences Preface 28 Integrated Ph D Programme in Chemical Sciences CD 29 Inorganic and Physical Chemistry IP 34 Materials Research MR 38 Organic Chemistry OC 41 Solid State and Structural Chemistry SS 44 III Division of Physical and Mathematical Sciences Preface 47 Instrumentation and Applied Physics IN 48 Mathematics MA 55 Astronomy and Astrophysics AA 69 Physics and Integrated Ph D in Physical Sciences PH 70 High Energy Physics HE 84 IV Division of Electrical Sciences Preface 89 Core requirements for M Tech Degree Programmes M Tech Degree - Computer Science and Engineering M Tech Degree - Telecommunications M Tech Degree – Signal Processing M Tech Degree – Microelectronics Systems M Tech Degree – Electrical Engineering M Tech Degree – Systems Science and Automation M Tech Degree – Electronics Systems Engineering Computer Science and Automation Intelligent Systems and Automation Communication Systems 1 Electronic Devices, Circuits and Technology Power Energy Systems High Voltage and Insulation Systems Electronics and Power Drives Photonic Device Electromagnetics, Microwaves and Antennas Signal Processing, Acoustics and Bioengineering Dissertation
    [Show full text]
  • BRCA1 and BRCA2 Germline Mutation Analysis Among Indian
    BRCA1 and BRCA2 mutations in India 415 BRCA1 and BRCA2 germline mutation analysis among Indian women from south India: identifi cation of four novel mutations and high-frequency occurrence of 185delAG mutation KANNAN VAIDYANATHAN1,#, SMITA LAKHOTIA1,#, H M RAVISHANKAR1,#, UMAIRA TABASSUM2, GEETASHREE MUKHERJEE2,* and KUMARAVEL SOMASUNDARAM1,* 1Department of Microbiology and Cell Biology, Indian Institute of Science, Bangalore 560 012, India 2Department of Pathology, Kidwai Memorial Institute of Oncology, Bangalore 560 068, India #Contributed equally *Corresponding author (Fax, 91-80-23602697; Email, [email protected]) Mutations in the BRCA1 and BRCA2 genes profoundly increase the risk of developing breast and/or ovarian cancer among women. To explore the contribution of BRCA1 and BRCA2 mutations in the development of hereditary breast cancer among Indian women, we carried out mutation analysis of the BRCA1 and BRCA2 genes in 61 breast or ovarian cancer patients from south India with a positive family history of breast and/or ovarian cancer. Mutation analysis was carried out using conformation-sensitive gel electrophoresis (CSGE) followed by sequencing. Mutations were identifi ed in 17 patients (28.0%); 15 (24.6%) had BRCA1 mutations and two (3.28%) had BRCA2 mutations. While no specifi c association between BRCA1 or BRCA2 mutations with cancer type was seen, mutations were more often seen in families with ovarian cancer. While 40% (4/10) and 30.8% (4/12) of families with ovarian or breast and ovarian cancer had mutations, only 23.1% (9/39) of families with breast cancer carried mutations in the BRCA1 and BRCA2 genes. In addition, while BRCA1 mutations were found in all age groups, BRCA2 mutations were found only in the age group of ≤40 years.
    [Show full text]
  • Creating an Effective Platform for Communication and Exchange
    COLLABORATION Creating an effective platform for communication and exchange KNOWLEDGE INTERCHANGE COMMUNICATION NETWORKING ADVANCEMENT The 2013 Annual Report of the Society for Neuro-Oncology Society for NeuroOncology This Annual Report covers the SNO 2013 fiscal year, from July 1st, 2012 through June 30, 2013. INTERCHANGE COLLABORATION COMMUNICATION EXCHANGE PERSPECTIVES A Message from the President INTERCHANGE Dear Colleagues and Friends, As the outgoing President, I am happy to share with you I would like to acknowledge some of the COLLABORATION some of the Society’s accomplishments and endeavors individuals who have contributed to the success of our during my tenure. To begin with, SNO continues to grow Society and by extension furthered the development COMMUNICATION with an overall increase in membership of 11% since of neuro-oncology as a field. First, much appreciation October 2012, with current membership now approaching goes to SNO Foundation members Mark Gilbert 1500 and representation from 42 countries. (chair), Mitchel Berger, Susan Chang and Victor Levin I am likewise happy to share that the impact factor of and members of the Partners Advisory Council for the Society’s official journal,Neuro-Oncology , continues their continued support and guidance as the Society to rise, now standing at 6.1, solidifying its reputation as continues to grow. I would also like to recognize the EXCHANGE the leading journal in the field. Its success is, in large part, members of the Board of Directors for their willingness due to the dedication of the editor-in-chief, W K Alfred to represent the diverse disciplines of the neuro- Yung who completes his successful tenure at the end of oncology community and for their input into critical PERSPECTIVES this year.
    [Show full text]
  • Elucidating the Cancer-Specific Genetic Alteration Spectrum of Glioblastoma Derived Cell Lines from Whole Exome and RNA Sequencing
    www.impactjournals.com/oncotarget/ Oncotarget, Vol. 6, No. 41 Elucidating the cancer-specific genetic alteration spectrum of glioblastoma derived cell lines from whole exome and RNA sequencing Vikas Patil1,*, Jagriti Pal1,* and Kumaravel Somasundaram1 1 Department of Microbiology and Cell Biology, Indian Institute of Science, Bangalore, India * These authors have contributed equally to this work Correspondence to: Kumaravel Somasundaram, email: [email protected] Keywords: glioblastoma, exome & RNA sequencing, cancer-specific mutations, gene fusions, RNA editing Received: May 03, 2015 Accepted: October 05, 2015 Published: October 19, 2015 This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. ABSTRACT Cell lines derived from tumor tissues have been used as a valuable system to study gene regulation and cancer development. Comprehensive characterization of the genetic background of cell lines could provide clues on novel genes responsible for carcinogenesis and help in choosing cell lines for particular studies. Here, we have carried out whole exome and RNA sequencing of commonly used glioblastoma (GBM) cell lines (U87, T98G, LN229, U343, U373 and LN18) to unearth single nucleotide variations (SNVs), indels, differential gene expression, gene fusions and RNA editing events. We obtained an average of 41,071 SNVs out of which 1,594 (3.88%) were potentially cancer-specific. The cell lines showed frequent SNVs and indels in some of the genes that are known to be altered in GBM- EGFR, TP53, PTEN, SPTA1 and NF1. Chromatin modifying genes- ATRX, MLL3, MLL4, SETD2 and SRCAP also showed alterations.
    [Show full text]
  • Awards Galore at DBT Foundation Day
    Awards galore at DBT Foundation Day 10 April 2007 | News Image not found or type unknown Awards galore at DBT Foundation Day On March 12, 2007, a series of awards were announced to honor researchers, scientists working in the sciences arena. The Distinguished Biotechnologist Award for the year 2006 has been conferred on Prof. TP Singh for his outstanding contributions in structural biology. Prof. TP Singh headed the Biophysics Department at the All India Institute of Medical Sciences, New Delhi during 1986–August 2006. He obtained his PhD from the Indian Institute of Science, Bangalore in 1975 on structure–function studies of analgesic/anti-inflammatory agents. He has made original and novel contributions to the structural studies of proteins and implemented a strong program on structure-based rational drug design. Significantly, Prof. TP Singh has developed a new program on Clinical Proteomics at AIIMS in collaboration with other faculty members to characterize all the proteins that are expressed during various patho/physiological conditions. His group has already determined more than 50 structures of proteins and their complexes under this program. Dr Manju Sharma, former secretary, DBT, has been honored with the National Award for Senior Woman Bioscientist for the year 2006 in recognition of her vision and incessant efforts in shaping and steering research in biotechnology and new biology and for applying research results for the benefit of the society in the country. The National Award for Young Women Bioscientists for the year 2006 was conferred on Dr Gagandeep Kang, CMC, Vellore and Dr Ramanathan Sowdhamini, NCBS, Bangalore. Dr Gagandeep Kang has been honored for her significant contributions on rotaviral diarrhoeal diseases in children particularly on molecular epidemiology.
    [Show full text]
  • Guidelines for the Use and Interpretation of Assays for Monitoring Autophagy (3Rd Edition)
    Guidelines for the use and interpretation of assays for monitoring autophagy (3rd edition) The MIT Faculty has made this article openly available. Please share how this access benefits you. Your story matters. Citation Klionsky, Daniel J., et al. “Guidelines for the Use and Interpretation of Assays for Monitoring Autophagy (3rd Edition).” Autophagy, vol. 12, no. 1, Jan. 2016, pp. 1–222. As Published http://dx.doi.org/10.1080/15548627.2015.1100356 Publisher Informa UK Limited Version Author's final manuscript Citable link http://hdl.handle.net/1721.1/116122 Terms of Use Creative Commons Attribution-Noncommercial-Share Alike Detailed Terms http://creativecommons.org/licenses/by-nc-sa/4.0/ AUTOPHAGY 2016, VOL. 12, NO. 1, 1–222 http://dx.doi.org/10.1080/15548627.2015.1100356 EDITORIAL Guidelines for the use and interpretation of assays for monitoring autophagy (3rd edition) Daniel J Klionsky1745,1749*, Kotb Abdelmohsen840, Akihisa Abe1237, Md Joynal Abedin1762, Hagai Abeliovich425, Abraham Acevedo Arozena789, Hiroaki Adachi1800, Christopher M Adams1669, Peter D Adams57, Khosrow Adeli1981, Peter J Adhihetty1625, Sharon G Adler700, Galila Agam67, Rajesh Agarwal1587, Manish K Aghi1537, Maria Agnello1826, Patrizia Agostinis664, Patricia V Aguilar1960, Julio Aguirre-Ghiso784,786, Edoardo M Airoldi89,422, Slimane Ait-Si-Ali1376, Takahiko Akematsu2010, Emmanuel T Akporiaye1097, Mohamed Al-Rubeai1394, Guillermo M Albaiceta1294, Chris Albanese363, Diego Albani561, Matthew L Albert517, Jesus Aldudo128, Hana Algul€ 1164, Mehrdad Alirezaei1198, Iraide
    [Show full text]
  • Current Excitements in Biochemistry and Molecular Biology for Agriculture and Medicine
    14th FAOBMB Congress and 84th Annual Meeting of SBC (I) Current Excitements in Biochemistry and Molecular Biology for Agriculture and Medicine Centre for Cellular and Molecular Biology, Hyderabad, India 27 – 30 November 2015 Programme Time (h) Day 1; Friday, 27 November 2015 11.00 - 13.00 Registration 12.30 - 13.30 Lunch 13.30 – 14.00 Inauguration 14.00 – 14.05 Announcement of President Elect, FAOBMB Plenary Lecture 1: Kanury V S Rao, India (Takashi Murachi Memorial Lecture) Deciphering the host-pathogen interplay in human macrophages infected with 14.05 - 14.45 Mycobacterium tuberculosis Chairperson: 14.45 - 15.25 Kiyoshi Fukui, Japan Plenary Lecture 2: Shubha Tole, India (Kunio Yagi Lecture) Towards a Blueprint for Building the Brain 15.25 - 15.55 Tea/Coffee Protein Folding and Disease Developmental Biology Epigenetics and miRNA 16.00 - 18.00 Chairperson: Masatsune Kainosho, Japan Chairperson: Polani B. Seshagiri, India Chairperson: K. Satyamoorthy, India L S. Shashidhara, India Manajit Hayer-Hartl, Germany Rakesh K. Mishra, India A comparative genomic analysis of targets of 16.00 - 16.30 The complex chaperone machineries for the Functional Compartmentalization of the Hox protein Ultrabithorax amongst distant folding and assembly of RuBisCO Genome and Epigenetic Regulation of Genes insect species: new insights into evolution of halteres in Drosophila Subramaniam Ganesh, India Tapas Kundu, India Kunihiro Kuwajima, Japan 16.30 - 17.00 Mitochondrial homeostasis and Lysine Acetylation and Arginine Methylation of The problem of protein folding
    [Show full text]
  • A Ten-Microrna Expression Signature Predicts Survival in Glioblastoma
    A Ten-microRNA Expression Signature Predicts Survival in Glioblastoma Sujaya Srinivasan, Irene Rosita Pia Patric, Kumaravel Somasundaram* Department of Microbiology and Cell Biology, Indian Institute of Science, Bangalore, Karnataka, India Abstract Glioblastoma (GBM) is the most common and aggressive primary brain tumor with very poor patient median survival. To identify a microRNA (miRNA) expression signature that can predict GBM patient survival, we analyzed the miRNA expression data of GBM patients (n = 222) derived from The Cancer Genome Atlas (TCGA) dataset. We divided the patients randomly into training and testing sets with equal number in each group. We identified 10 significant miRNAs using Cox regression analysis on the training set and formulated a risk score based on the expression signature of these miRNAs that segregated the patients into high and low risk groups with significantly different survival times (hazard ratio [HR] = 2.4; 95% CI = 1.4–3.8; p,0.0001). Of these 10 miRNAs, 7 were found to be risky miRNAs and 3 were found to be protective. This signature was independently validated in the testing set (HR = 1.7; 95% CI = 1.1–2.8; p = 0.002). GBM patients with high risk scores had overall poor survival compared to the patients with low risk scores. Overall survival among the entire patient set was 35.0% at 2 years, 21.5% at 3 years, 18.5% at 4 years and 11.8% at 5 years in the low risk group, versus 11.0%, 5.5%, 0.0 and 0.0% respectively in the high risk group (HR = 2.0; 95% CI = 1.4–2.8; p,0.0001).
    [Show full text]
  • Book Download
    SOCIETY OF BIOLOGICAL CHEMISTS (INDIA) (1930 – 2011) 1 TABLE OF CONTENTS 1. Goals and activities of SBC(I) 2. Rules and Bye-laws of SBC(I) 3. Past Presidents, Secretaries, Treasurers (with tenure) 4. “Reminiscences on the development of the Society of Biological Chemists (India): a personal perspective” by Prof. N. Appaji Rao 5. “Growth of Biochemistry in India” by Prof. G. Padmanaban 6. Current office bearers 7. Current Executive Committee Members 8. Office staff 9. Past meeting venues of SBC(I) 10. SBC(I) awards, criteria and procedure for applying 11. SBC(I) awardees 12. Current list of life members with address 13. Acknowledgments 2 GOALS AND ACTIVITIES OF SBC(I) To meet a long felt need of scientists working in the discipline of biological chemistry " The Society Of Biological Chemists (India)" was founded in 1930, with its Head Quarters at Indian Institute of Science, Bangalore. It was registered under the Societies Act in the then princely state of Mysore and the memorandum of registration was signed by the late Profs. V. Subramanian, V. N. Patwardhan and C. V. Natarajan, who were leading personalities in the scientific firmament during that period. The Society played a crucial role during the Second World War by advising the Government on the utilization of indigenous biomaterials as food substitutes, drugs and tonics, on the industrial and agricultural waste utilization and on management of water resources. The other areas of vital interest to the Society in the early years were nutrition, proteins, enzymes, applied microbiology, preventive medicines and the development of high quality proteins from indigenous plant sources.
    [Show full text]
  • Activation of Multiple Signalling Pathways by P152lp53 Mutant Reveals New Gain-Of-Function Implicating Tumorigenesis
    bioRxiv preprint doi: https://doi.org/10.1101/475293; this version posted November 20, 2018. The copyright holder for this preprint (which was not certified by peer review) is the author/funder. All rights reserved. No reuse allowed without permission. Activation of Multiple Signalling Pathways by P152Lp53 Mutant Reveals New Gain-of-function Implicating Tumorigenesis Siddharth Singh1*, Manoj Kumar1*&, Sanjeev Kumar2*, Shrinka Sen1, Pawan Upadhyay3, Naveen M2, Vivek S. Tomar 4, Amit Dutt3 and Tapas K. Kundu1 1Transcription and Disease Laboratory, Molecular Biology and Genetics Unit, Jawaharlal Nehru Centre for Advanced Scientific Research, Bengaluru-560 064, India 2BioCOS Life Sciences Pvt. Ltd. Bengaluru, India 3 Integrated Cancer Genomics Lab, Advanced Centre for Treatment, Research and Education in Cancer, Tata Memorial Center, Navi Mumbai, India 4Department of Microbiology and Cell Biology, Indian Institute of Science, Bengaluru-560 012, India. & Present address: School of Biological and Environmental Sciences,Faculty of Basic Sciences, Shoolini University, Solan, Himachal Pradesh, India *Authors contributed equally to this manuscript Conflict of interest: The authors declare no potential conflicts of interest. Significance: This study for the first time carried out extensive biochemical and functional characterization of P152Lp53 and established it as a new Gain-of-function mutant which is conformationally altered. Corresponding author: Prof. Tapas K. Kundu, Transcription and Disease Laboratory, Molecular and Genetics Unit, JNCASR, Jakkur P.O., Bengaluru-560064, India. Ph: 91-80-22082840/2841 Email: [email protected] Running Title: A Gain-of-function mutant p53 (P152L) Keywords: DNA Binding, p53 tetramerization, P152L, Tumor suppressor, Carcinogenesis 1 bioRxiv preprint doi: https://doi.org/10.1101/475293; this version posted November 20, 2018.
    [Show full text]
  • CRP-Ongoing Projects Data.Pdf
    Project Indian PI First Indian PI Last French PI First French PI last S.No. Title of the project Indian Institution City French Institution City No Name Name Name Name Studying the role of rpoN, the INRA Laboratoire des Castanet 4800- alternative sigma factor, in the Prof. Suvendra 1 Ray Tezpur University Tezpur Dr. Stéphane Genin Interactions Plantes Micro- Tolosan B1 pathogenicity of R. solanacearum, the Kumar organisms- Cedex causal agent of bacterial wilt in plants National Centre for Biological INSERM (Institut National de la Muscle SC self-renewal: A stressful Sciences, TIFR, Institute for 2 5003-1 Prof. Jyotsna Dhawan Bangalore Dr Ana FERREIRO Santé et la Recherche Paris matter? Stem Cell Biology and Médicale) Regenerative Medicine Advanced Computational Models to Indian Institute of Science Mohanpur, Institut de Recherches en 3 5004-1 Facilitate Solar Activity and Space Dr. Dibyendu Nandi Dr. Laurène JOUVE Toulouse Education and Research, Kolkata Astrophysique et Planétologie Weather Predictions Influence of the Resorcin[4]arene on Tiruchirappali 4 5005-1 Dr. R. Ramesh Bharathidasan University Dr. D. Sémeril Université de Strasbourg Strasbourg the Catalytic Outcomes , Tamil Nadu Design and synthesis of new C1‐ ECPM University of symmetric biaryl‐based ligands and Strasbourg, UMR 5 5005-2 Dr. Pradeep Kumar National Chemical Laboratory Pune Dr. Frédéric LEROUX Strasbourg catalysts and their evaluation in 7509/CNRS/ECPM – Chimie asymmetric catalytic reactions Moléculaire The Immuno-Psychiatry in South India Jawaharlal Institute of Study (IPS): Immunogenetic and INSERM U 942, Saint Louis 6 5103-1 Dr. Vir Singh Negi Postgraduate Medical Pondicherry Dr. Ryad Tamouza Paris Immuno-phenotype Characterization Hospital Education and Research of Major Psychoses TIFR National Centre for (CSGA) UMR- 7 5103-2 Olfactory Modulation of Insect Flight Prof.
    [Show full text]
  • 37Th IACR Convention
    37th IACR Convention From Cancer Biology to Precision Oncology: Challenges and Considerations Jointly Organized by Indian Association of Cancer Research & Bose Institute, National Institute of Biomedical Genomics, Indian Statistical Institute, Indian Institute of Chemical Biology, IIT-KGP, IPGMR, Saha Institute of Nuclear Physics, IISER-Kolkata, Chittaranjan National Cancer Institute, Saroj Gupta Cancer Centre, Burdwan University, University of Calcutta 23rd- 25th February, 2018, Bose Institute, Unified Academic Campus, EN block, Salt Lake, Kolkata Programme 23rd February, 2018 08.30 am-09.30 am Registration 09.30 am-10.00 am Inauguration (Auditorium) SESSION 1 Chair: Prof. Partha P. Majumder 10:00am - 11:00 am IACR Oration & Institute Day Address of the National Institute of Biomedical Genomics, Kalyani Using Genomics to Inform Care of Patients with Cancer Peter Campbell 11:00am-11:30am Mapp Tea Break SESSION 2 Chair: Prof. Siddhartha Roy and Prof. Samit Chattopadhyay 11:30am – 11:50am INOVATe: a step closer to precision treatment for women with epithelial ovarian cancer Anna deFazio 1 11:50am -12:10 pm Genetic landscape of Indian gliomas: Defective neuroactive ligand-receptor interaction pathway identifies glioblastoma with poor survival Kumaravel Somasundaram 12:10pm-12:30pm Axonal Guidance Proteins in Tumorigenesis: Role of Genetic Status of KRAS and TGF-b1 Signaling Pathway Debabrata (Dev) Mukhopadhyay 12.30 pm-1.30 pm Poster Session (Hallway) [ Poster numbers 1-25 + 25 posters for Baxi and Kulkarni Awards] 1.30 pm-2.30 pm Lunch Invited Lecture (Hall-A; 2.30 pm – 5.10 pm) SESSION 3 Chair: Dr. Kunal Ray & Dr. Arindam Maitra (AGILENT sponsored session) 2.30 pm - 2.50 pm IL-01.
    [Show full text]