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Grant Details

Grant Number: 5R01CA163705-05 Interpret this number
Primary Investigator: Burns, Kathleen
Organization: Johns Hopkins University
Project Title: Transposon Insertion Polymorphisms in Predispositions to Hematopoietic Neoplasia
Fiscal Year: 2017
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Abstract

DESCRIPTION (provided by applicant): Our genomes are mostly made up of repetitive 'junk DNA' derived from insertions of sequences through RNA intermediates. Our group has developed methods to identify polymorphic insertions of these understudied sequences, demonstrated they are major sources of structural variation our genome, and found they occur frequently in LD with trait associated SNPs identified by cancer genome wide association study (GWAS). Experiments by others and characterizations of the non-random distribution of mobile DNAs in our genome indicate they have significant potential to effect gene function. The overarching hypothesis of this proposal is that a subset of common mobile DNA insertions predispose to common cancer development. Our three part approach to test this hypothesis will include: (i.) identification of RIPs with potential roles in neoplasia by locating those in the vicnity of regions implicated in disease risk by GWAS; (ii.) determining which of these RIPs may reasonably account for cancer risk by analyses of area linkage and RIP genotype imputing in clinical samples; and (iii.) investigating effects of transposon polymorphisms on transcript expression levels and structure. Hematopoietic malignancies will receive special priority in these studies, and clinical samples from patients with leukemias, lymphomas, and related disordered will be used for a directed RIP discovery effort and for evaluating mechanisms of gene expression effects.

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Publications

Structural variants caused by Alu insertions are associated with risks for many human diseases.
Authors: Payer L.M. , Steranka J.P. , Yang W.R. , Kryatova M. , Medabalimi S. , Ardeljan D. , Liu C. , Boeke J.D. , Avramopoulos D. , Burns K.H. .
Source: Proceedings Of The National Academy Of Sciences Of The United States Of America, 2017-05-16 00:00:00.0; 114(20), p. E3984-E3992.
EPub date: 2017-05-02 00:00:00.0.
PMID: 28465436
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The Human Long Interspersed Element-1 Retrotransposon: An Emerging Biomarker of Neoplasia.
Authors: Ardeljan D. , Taylor M.S. , Ting D.T. , Burns K.H. .
Source: Clinical Chemistry, 2017 Apr; 63(4), p. 816-822.
EPub date: 2017-02-10 00:00:00.0.
PMID: 28188229
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Human Transposon Insertion Profiling: Analysis, Visualization And Identification Of Somatic Line-1 Insertions In Ovarian Cancer
Authors: Tang Z. , Steranka J.P. , Ma S. , Grivainis M. , Rodiż N. , Huang C.R. , Shih I.M. , Wang T.L. , Boeke J.D. , Fenyö D. , et al. .
Source: Proceedings Of The National Academy Of Sciences Of The United States Of America, 2017-01-31 00:00:00.0; 114(5), p. E733-E740.
PMID: 28096347
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Somatically Acquired LINE-1 Insertions in Normal Esophagus Undergo Clonal Expansion in Esophageal Squamous Cell Carcinoma.
Authors: Doucet-O'Hare T.T. , Sharma R. , Rodi? N. , Anders R.A. , Burns K.H. , Kazazian H.H. .
Source: Human Mutation, 2016 Sep; 37(9), p. 942-54.
EPub date: 2016-07-13 00:00:00.0.
PMID: 27319353
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Meeting Report: The Role Of The Mobilome In Cancer
Authors: Ardeljan D. , Taylor M.S. , Burns K.H. , Boeke J.D. , Espey M.G. , Woodhouse E.C. , Howcroft T.K. .
Source: Cancer Research, 2016-08-01 00:00:00.0; 76(15), p. 4316-9.
PMID: 27527733
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Genome-wide Characterization Of Human L1 Antisense Promoter-driven Transcripts
Authors: Criscione S.W. , Theodosakis N. , Micevic G. , Cornish T.C. , Burns K.H. , Neretti N. , Rodiż N. .
Source: Bmc Genomics, 2016-06-14 00:00:00.0; 17, p. 463.
PMID: 27301971
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A Robust Nonlinear Tissue-component Discrimination Method For Computational Pathology
Authors: Sarnecki J.S. , Burns K.H. , Wood L.D. , Waters K.M. , Hruban R.H. , Wirtz D. , Wu P.H. .
Source: Laboratory Investigation; A Journal Of Technical Methods And Pathology, 2016 Apr; 96(4), p. 450-8.
PMID: 26779829
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Immunodetection of Human LINE-1 Expression in Cultured Cells and Human Tissues.
Authors: Sharma R. , Rodiż N. , Burns K.H. , Taylor M.S. .
Source: Methods In Molecular Biology (clifton, N.j.), 2016; 1400, p. 261-80.
PMID: 26895059
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Characterization of L1-Ribonucleoprotein Particles.
Authors: Taylor M.S. , LaCava J. , Dai L. , Mita P. , Burns K.H. , Rout M.P. , Boeke J.D. .
Source: Methods In Molecular Biology (clifton, N.j.), 2016; 1400, p. 311-38.
PMID: 26895062
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A Map Of Mobile Dna Insertions In The Nci-60 Human Cancer Cell Panel
Authors: Zampella J.G. , Rodiż N. , Yang W.R. , Huang C.R. , Welch J. , Gnanakkan V.P. , Cornish T.C. , Boeke J.D. , Burns K.H. .
Source: Mobile Dna, 2016; 7, p. 20.
PMID: 27807467
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Somatic Retrotransposition Is Infrequent In Glioblastomas
Authors: Achanta P. , Steranka J.P. , Tang Z. , Rodiż N. , Sharma R. , Yang W.R. , Ma S. , Grivainis M. , Huang C.R. , Schneider A.M. , et al. .
Source: Mobile Dna, 2016; 7, p. 22.
PMID: 27843500
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Retrotransposon insertions in the clonal evolution of pancreatic ductal adenocarcinoma.
Authors: Rodiż N. , Steranka J.P. , Makohon-Moore A. , Moyer A. , Shen P. , Sharma R. , Kohutek Z.A. , Huang C.R. , Ahn D. , Mita P. , et al. .
Source: Nature Medicine, 2015 Sep; 21(9), p. 1060-4.
PMID: 26259033
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LINE-1 expression and retrotransposition in Barrett's esophagus and esophageal carcinoma.
Authors: Doucet-O'Hare T.T. , Rodiż N. , Sharma R. , Darbari I. , Abril G. , Choi J.A. , Young Ahn J. , Cheng Y. , Anders R.A. , Burns K.H. , et al. .
Source: Proceedings Of The National Academy Of Sciences Of The United States Of America, 2015-09-01 00:00:00.0; 112(35), p. E4894-900.
EPub date: 2015-09-01 00:00:00.0.
PMID: 26283398
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Visualization and probability-based scoring of structural variants within repetitive sequences.
Authors: Halper-Stromberg E. , Steranka J. , Burns K.H. , Sabunciyan S. , Irizarry R.A. .
Source: Bioinformatics (oxford, England), 2014-06-01 00:00:00.0; 30(11), p. 1514-21.
EPub date: 2014-06-01 00:00:00.0.
PMID: 24501098
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Long interspersed element-1 protein expression is a hallmark of many human cancers.
Authors: Rodiż N. , Sharma R. , Sharma R. , Zampella J. , Dai L. , Taylor M.S. , Hruban R.H. , Iacobuzio-Donahue C.A. , Maitra A. , Torbenson M.S. , et al. .
Source: The American Journal Of Pathology, 2014 May; 184(5), p. 1280-6.
PMID: 24607009
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TE-array--a high throughput tool to study transposon transcription.
Authors: Gnanakkan V.P. , Jaffe A.E. , Dai L. , Fu J. , Wheelan S.J. , Levitsky H.I. , Boeke J.D. , Burns K.H. .
Source: Bmc Genomics, 2013-12-10 00:00:00.0; 14, p. 869.
EPub date: 2013-12-10 00:00:00.0.
PMID: 24325565
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Affinity Proteomics Reveals Human Host Factors Implicated In Discrete Stages Of Line-1 Retrotransposition
Authors: Taylor M.S. , LaCava J. , Mita P. , Molloy K.R. , Huang C.R. , Li D. , Adney E.M. , Jiang H. , Burns K.H. , Chait B.T. , et al. .
Source: Cell, 2013-11-21 00:00:00.0; 155(5), p. 1034-48.
PMID: 24267889
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Translocation junctions in TCF3-PBX1 acute lymphoblastic leukemia/lymphoma cluster near transposable elements.
Authors: Rodiż N. , Zampella J.G. , Cornish T.C. , Wheelan S.J. , Burns K.H. .
Source: Mobile Dna, 2013-10-17 00:00:00.0; 4(1), p. 22.
EPub date: 2013-10-17 00:00:00.0.
PMID: 24135088
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Functional impact of the human mobilome.
Authors: Babatz T.D. , Burns K.H. .
Source: Current Opinion In Genetics & Development, 2013 Jun; 23(3), p. 264-70.
PMID: 23523050
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Long Interspersed Element-1 (line-1): Passenger Or Driver In Human Neoplasms?
Authors: Rodiż N. , Burns K.H. .
Source: Plos Genetics, 2013 Mar; 9(3), p. e1003402.
PMID: 23555307
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